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1.
Int J Gen Med ; 17: 4407-4418, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355341

RESUMO

Background and Aims: The red blood cell distribution width (RDW) to albumin (ALB) ratio (RAR) has been identified as a prognostic indicator for mortality in critically ill patients across various diseases. Nevertheless, the impact of RAR on clinical functional prognosis in Acute ischemic stroke (AIS) remains uncertain. This study aimed to evaluate the prognostic significance of RAR in AIS patients. Methods: A secondary analysis was performed on a cohort study, involving 1906 AIS patients recruited from a South Korean academic hospital. Both univariate and multivariate logistic regression was employed to assess the connections between RAR and negative functional results in AIS. To explore potential non-linear relationships in this association, a generalized additive model (GAM) and smooth curve fitting were utilized. Further, a mediation analysis was performed to identify possible mediators. Results: Out of the 1906 eligible patients, 546 (28.65%) were found to have an unfavorable prognosis. Patients with elevated RAR had a higher likelihood of facing a negative prognosis in AIS (all P<0.001). RAR demonstrated a dose-response relationship with the probability of poor functional prognosis. When analysis of RAR as a continuous variable, an increase in RAR was correlated with a higher risk of adverse prognosis.When RAR was analyzed as quartile variables, the highest RAR remained an independent contributing factor for both 3-month unfavorable outcomes (adjusted OR, 1.4; 95% CI: 1.0-2.1, P=0.046) and 3-month mortality (adjusted OR, 5.2; 95% CI, 2.0-13.9; p<0.001). More interestingly, the presence of a pro-inflammatory state may serve as a mediator in the connections between RAR and adverse functional outcomes. Conclusion: Given its cost-effectiveness and ease of measurement, baseline RAR holds promise as a valuable biomarker for early risk assessment in AIS patients.

2.
Biomed Pharmacother ; 179: 117402, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39243428

RESUMO

In recent years, the integration of radiotherapy and nanocatalytic medicine has gained widespread attention in the treatment of breast cancer. Herein, the glucose oxidase (GOx) and MnO2 nanoparticles co-modified multifunctional liposome of GOx-MnO2@Lip was constructed for enhanced radiotherapy. Introduction of GOx would not only elevate the glucose consumption to starve the cancer cells, but also increased the endogenous H2O2 level. Meanwhile, high intracellular GSH concentration facilitated the release of Mn2+ to amplify the cytotoxic ·OH through cascade catalytic reactions within the tumor microenvironment, resulting in a favorable tumor suppression rate of 74.45 %. Furthermore, the blood biochemical and blood routine demonstrated that GOx-MnO2@Lip had no obvious toxic side effects. Therefore, this work provided a potential vehicle for synergistic cancer starving therapy, chemodynamic therapy and radiotherapy for improving therapeutic efficacy of breast cancer.


Assuntos
Neoplasias da Mama , Glucose Oxidase , Lipossomos , Compostos de Manganês , Óxidos , Radiossensibilizantes , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Glucose Oxidase/metabolismo , Feminino , Óxidos/química , Óxidos/farmacologia , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Radiossensibilizantes/farmacologia , Animais , Humanos , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos BALB C , Catálise , Camundongos , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacos
3.
Curr Med Sci ; 44(4): 854-863, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39112916

RESUMO

OBJECTIVE: This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide (LPS) and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses. METHODS: PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25, 0.5, 0.75, 1, and 1.25 mg/mL for 24 h. Cell morphology was evaluated, and cell survival rates were calculated. A neurocyte inflammatory model was established with LPS treatment, which reached a 50% cell survival rate. PC12 cells were treated with 0.01, 0.1, 1, 10, or 100 µmol/L astragaloside IV for 24 h. The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments. NOS activity was detected by colorimetry; the expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting. The differentially expressed genes (DEGs) between the groups were screened using a second-generation sequence (fold change>2, P<0.05) with the following KEGG enrichment analysis, RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells. RESULTS: The viability of PC12 cells was not altered by treatment with 0.01, 0.1, or 1 µmol/L astragaloside IV for 24 h (P>0.05). However, after treatment with 0.5, 0.75, 1, or 1.25 mg/mL LPS for 24 h, the viability steadily decreased (P<0.01). The mRNA and protein expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS, and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h (P<0.01); however, these changes were reversed when PC12 cells were pretreated with 0.01, 0.1, or 1 µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h (P<0.05). Second-generation sequencing revealed that 1026 genes were upregulated, while 1287 genes were downregulated. The DEGs were associated with autophagy, TNF-α, interleukin-17, MAPK, P53, Toll-like receptor, and NOD-like receptor signaling pathways. Furthermore, PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2, CCL11, CCL7, MMP3, and MMP10, which are associated with the IL-17 pathway. RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results. CONCLUSION: LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage. astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.


Assuntos
Anti-Inflamatórios , Sobrevivência Celular , Reparo do DNA , Lipopolissacarídeos , Saponinas , Triterpenos , Animais , Células PC12 , Ratos , Lipopolissacarídeos/farmacologia , Triterpenos/farmacologia , Saponinas/farmacologia , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos
4.
J Asian Nat Prod Res ; : 1-21, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132822

RESUMO

This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3ß phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3ß signaling pathway.

5.
Sci Rep ; 14(1): 10745, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730240

RESUMO

Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Ferroptose , Flavonoides , Oxaliplatina , Neoplasias Gástricas , Proteína Supressora de Tumor p53 , Ferroptose/efeitos dos fármacos , Humanos , Flavonoides/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Oxaliplatina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Sinergismo Farmacológico , Espécies Reativas de Oxigênio/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38814604

RESUMO

Objective: To investigate the risk factors for lung infection in lung cancer patients undergoing radiotherapy. Methods: We selected 142 patients with lung cancer who underwent radiotherapy at our hospital from January 2020 to June 2021. The patients were divided into groups according to whether they had pulmonary infection during radiotherapy in our hospital, which was infected group (n=44) and the uninfected group (n=98), respectively. To observe the incidence of lung infection in lung cancer patients during radiotherapy. The distribution of pathogenic bacteria in patients with pulmonary infection was observed. Clinical data of the two groups were collected and compared. The risk factors of lung cancer patients complicated with lung infection were analyzed by binary Logistic regression. Results: All patients with lung cancer complicated with lung infection underwent relevant examination, and the results showed that they were all complicated infections, and the composition ratio of Klebsiella pneumoniae was the highest (31.82%), followed by Staphylococcus, Pseudomonas, and fungi, which accounted for 27.27%, 22.73%, and 18.18%, respectively. Binary Logistic regression analysis showed that age ≥60 years old, smoking history ≥30 years, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L were risk factors for lung cancer patients during radiotherapy. Conclusion: Age ≥60 years old, smoking history ≥30 years old, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L are the risk factors for lung cancer patients during radiotherapy. Clinical prevention and intervention should be based on the aforementioned independent risk factors to decrease the incidence of lung infections, thereby enhancing patient prognosis.

7.
ACS Omega ; 9(14): 15753-15767, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617672

RESUMO

Tumors are one of the main diseases threatening human life and health. The emergence of nanotechnology in recent years has introduced a novel therapeutic avenue for addressing tumors. Through the amalgamation of nanotechnology's inherent attributes with those of natural enzymes, nanozymes have demonstrated the ability to initiate catalytic reactions, modulate the biological microenvironment, and facilitate the adoption of multifaceted therapeutic approaches, thereby exhibiting considerable promise in the realm of cancer treatment. In this Review, the application of nanozymes in chemodynamic therapy, radiotherapy, photodynamic therapy, photothermal therapy, and starvation therapy are summarized. Moreover, a detailed discussion regarding the mechanism of conferring physiotherapeutic functionality upon catalytic nanosystems is provided. It is posited that this innovative catalytic treatment holds significant potential to play a crucial role within the domain of nanomedicine.

8.
Arab J Gastroenterol ; 25(1): 42-50, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38220481

RESUMO

BACKGROUND AND STUDY AIMS: MicroRNA (miRNA) is involved in diverse biological and physiological processes of tumors. Dysregulation of miRNA will induce a series of human diseases. miR-129-2-3p has vital effects in the pathogenesis of various tumors. However, the regulatory function of miR-129-2-3p in colon cancer remains to be clarified. This study investigated the role of miR-129-2-3p targeting BZW1 in proliferation, apoptosis, migration, and invasion of colon cancer. PATIENTS AND METHODS: Here, RT-qPCR was applied to measure the miR-129-2-3p levels in colon cancer tissues. The predicted targets of miR-129-2-3p were identified by bioinformatics and verified using luciferase reporter assay. The effects of miR-129-2-3p on colon cancer were detected by CCK-8, colony formation, transwell chamber test, wound healing, and flow cytometry assays. Finally, the influence of miR-129-2-3p on tumor growth was studied. Nude mice were xenografted with transfected Lovo cells by subcutaneous injection of 5 × 105 cells in 100 µl. HE staining and TUNEL were used to assess metastasis ability. RESULTS: miR-129-2-3p level in colon cancer tissue was significantly reduced. Furthermore, it was verified that BZW1 was a target of miR-129-2-3p, and its expression in colon cancer cells was inhibited by miR-129-2-3p. Additionally, miR-129-2-3p inhibited colon cancer cell proliferation, colony formation, mobility ability and tumor growth, and promoted cell apoptosis by targeting BZW1. miR-129-2-3p overexpression in tumor xenografts in vivo decreased BZW1 expression, and suppressed tumor growth. CONCLUSION: Collectively, these findings indicated that miR-129-2-3p exerts a suppressive role in colon cancer cells by directly targeting BZW1, and may have significant therapeutic implications for patients with colon cancer.


Assuntos
Neoplasias do Colo , MicroRNAs , Animais , Camundongos , Humanos , Camundongos Nus , Linhagem Celular Tumoral , MicroRNAs/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
10.
Sci Rep ; 13(1): 20380, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990105

RESUMO

This study was designed to evaluate the prognosis and pharmacological therapy sensitivity of epithelial mesenchymal transition-related genes (EMTRGs) that obtained from the EMTome database in hepatocellular carcinoma (HCC) using bioinformatical method. The expression status of EMTRGs were also investigated using the clinical information of HCC patients supported by TCGA database and the ICGC database to establish the TCGA cohort as the training set and the ICGC cohort as the validation set. Analyze the EMTRGs between HCC tissue and liver tissue in the TCGA cohort in the order of univariate COX regression, LASSO regression, and multivariate COX regression, and construct a risk model for EMTRGs. In addition, enrichment pathways, gene mutation status, immune infiltration, and response to drugs were also analyzed in the high-risk and low-risk groups of the TCGA cohort, and the protein expression status of EMTRGs was verified. The results showed a total of 286 differentially expressed EMTRGs in the TCGA cohort, and EZH2, S100A9, TNFRSF11B, SPINK5, and CCL21 were used for modeling. The TCGA cohort was found to have a worse outcome in the high-risk group of HCC patients, and the ICGC cohort confirmed this finding. In addition, EMTRGs risk score was shown to be an independent prognostic factor in both cohorts by univariate and multivariate COX regression. The results of GSEA analysis showed that most of the enriched pathways in the high-risk group were associated with tumor, and the pathways enriched in the low-risk group were mainly associated with metabolism. Patients in various risk groups had varying immunological conditions, and the high-risk group might benefit more from targeted treatments. To sum up, the EMTRGs risk model was developed to forecast the prognosis for HCC patients, and the model might be useful in assisting in the choice of treatment drugs for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Prognóstico , Fatores de Risco
11.
ACS Appl Mater Interfaces ; 15(48): 56454-56463, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37982666

RESUMO

The combination of continuous fiber-reinforced thermoplastic composites (CFRTPCs) and the continuous fiber 3D printing (CF3DP) technique enables the rapid production of complex structural composites. In these 3D-printed composites, stress transfer primarily relies on the fiber-resin interface, making it a critical performance factor. The interfacial properties are significantly influenced by the temperatures applied during the loading and forming processes. While the effect of the loading temperature has been extensively researched, that of the forming temperature remains largely unexplored, especially from an atomistic perspective. Our research aims to employ molecular dynamics simulations to elucidate the effect of temperature on the interfacial properties of continuous carbon fiber-reinforced polyamide 6 (C/PA6) composites fabricated using the CF3DP technique, considering both loading and forming aspects. Through molecular dynamics simulations, we uncovered a positive correlation between the interfacial strength and forming temperature. Moreover, an increased forming temperature induced a notable shift in the failure mode of C/PA6 under uniaxial tensile loading. Furthermore, it was observed that increasing loading temperatures led to the deterioration of the mechanical properties of PA6, resulting in a gradual transition of the primary failure mode from adhesive failure to cohesive failure. This shift in the failure mode is closely associated with the glass transition of PA6.

12.
Proc Natl Acad Sci U S A ; 120(40): e2311755120, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748078

RESUMO

Soft materials that can produce electrical energy under mechanical stimulus or deform significantly via moderate electrical fields are important for applications ranging from soft robotics to biomedical science. Piezoelectricity, the property that would ostensibly promise such a realization, is notably absent from typical soft matter. Flexoelectricity is an alternative form of electromechanical coupling that universally exists in all dielectrics and can generate electricity under nonuniform deformation such as flexure and conversely, a deformation under inhomogeneous electrical fields. The flexoelectric coupling effect is, however, rather modest for most materials and thus remains a critical bottleneck. In this work, we argue that a significant emergent flexoelectric response can be obtained by leveraging a hierarchical porous structure found in biological materials. We experimentally illustrate our thesis for a natural dry luffa vegetable-based sponge and demonstrate an extraordinarily large mass- and deformability-specific electromechanical response with the highest-density-specific equivalent piezoelectric coefficient known for any material (50 times that of polyvinylidene fluoride and more than 10 times that of lead zirconate titanate). Finally, we demonstrate the application of the fabricated natural sponge as green, biodegradable flexible smart devices in the context of sensing (e.g., for speech, touch pressure) and electrical energy harvesting.

13.
Front Pharmacol ; 14: 1225256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601067

RESUMO

Introduction: The oil palm kernel (OPK) expeller is the main byproduct of palm oil, but its utilization is limited. Methods: To obtain angiotensin-I-converting enzyme (ACE) inhibition peptides with Zn-chelating capacity, defatted oil palm kernel globulin hydrolysates (DOPKGH) were subjected to Sephadex G-15 gel electrophoresis, reverse-phase high liquid performance chromatography, and UPLC-ESI-MS/MS analysis. Results and discussion: Five representative oligopeptides, including Gln-Arg-Leu-Asp-Arg-Cys-Lys (QRLERCK), Leu-Leu-Leu-Gly-Val-Ala-Asn-Tyr-Arg (LLLGVANYR), Arg-Ala-Asp-Val-Phe-Asn-Pro-Arg (RADVFNPR), Arg-Val-Ile-Lys-Tyr-Asn-Gly-Gly-Gly-Ser-Gly (RVIKYNGGGSG), and Glu-Val-Pro-Gln-Ala-Tyr-Ile-Pro (EVPQAYIP), without potential toxicity and allergenicity, were identified in DOPKGH. Of these, only EVPQAYIP showed both ACE-inhibitory activity (IC50: 102.75 µmol/L) and Zn-chelating capacity (11.69 mg/g). Molecular docking and inhibition kinetics showed that EVPQAYIP was a competitive inhibitor of ACE because it could bind to Glu384, Lys511, and Gln281 (belonging to the central S1 and S2 pockets, respectively) of ACE. Moreover, EVPQAYIP affects zinc tetrahedral coordination in ACE by binding to Glu411; the amino and carboxyl groups of EVPQAYIP chelate with zinc ions. During gastrointestinal digestion, the ACE inhibitory activity of EVPQAYIP was relatively stable. Additionally, EVPQAYIP enhanced zinc stability in the intestine and exerted antihypertensive effects in spontaneous hypertensive rats. These results suggest the potential application of OPK peptides as ingredients in antihypertensive agents or zinc fortification.

14.
Am J Transl Res ; 15(5): 3697-3704, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303679

RESUMO

OBJECTIVE: To construct a predictive model for the risk of rebleeding in non-variceal upper gastrointestinal bleeding (NVUGIB) based on multidimensional indicators to provide an assessment tool for early screening of rebleeding in NVUGIB. METHODS: Retrospective analysis of the 3-month follow-up data of 85 patients with NVUGIB diagnosed at the Fifth Hospital of Wuhan from January 2019 to December 2021 who were discharged from the hospital after medical treatment. Patients were divided into a rebleeding group (n=45) and a non-rebleeding group (n=95) based on whether they rebleed during follow-up. The demographic characteristics, clinical characteristics and biochemical indicators of the two groups were compared. A multivariate logistic regression was used to analyze the influencing factors of NVUGIB rebleeding. A nomograph model was built using the screening results. The area under the working characteristic curve of the subject (AUC) was used to analyze the model differentiation, evaluate the model specificity and sensitivity, and verify the prediction performance of the model with the validation set. RESULTS: There were significant differences in age, hematemesis, red blood cell count (RBC), platelet (PLT), albumin (Alb), prothrombin time (PT), TT, fibrinogen (Fib), plasma D-dimer (D-D), and blood lactate (LAC) levels between the two groups (all P<0.05). Logistic regression analysis shows that, age ≥75, hematemesis more than 5 times, PLT≤100*109/L, D-D>0.5 mg/L were associated with greater risk of rebleeding. The nomogram model was constructed based on the above four indicators. The AUC of the training set (n=98) for predicting the risk of NVUGIB rebleeding was 0.887 (95% CI: 0.812-0.962), the specificity was 0.882, and the sensitivity was 0.833. The AUC of the validation set (n=42) was 0.881 (95% CI: 0.777-0.986), the specificity was 0.815, and the sensitivity was 0.867. After 500 times of sampling by bootstrap method, the mean absolute error of the calibration curve of the validation set model was 0.031, indicating that the calibration curve and the ideal curve fit well, and the predicted value of the model was in good agreement with the actual value. CONCLUSION: Age ≥75, hematemesis >5 times, lower PLT, and higher D-D levels rise the risk of rebleeding in NVUGIB patients and have some reference value in clinical diagnosis and disease assessment.

15.
Int J Mol Med ; 52(2)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37387415

RESUMO

Tumor multidrug resistance (MDR) remains one of the most challenging barriers to successful cancer treatment. Several previous studies have suggested that high mobility group box 1 (HMGB1) may be a promising therapeutic target for overcoming cancer drug resistance. Emerging evidence has indicated that HMGB1 functions as a 'double­edged sword' that plays both pro­ and anti­tumor roles in the development and progression of multiple types of cancer. HMGB1 has also been found to be a key regulator of several cell death and signaling pathways, and is involved in MDR by mediating cell autophagy and apoptosis, ferroptosis, pyroptosis and multiple signaling pathways. Additionally, HMGB1 is regulated by a variety of non­coding RNAs (ncRNAs), such as microRNAs, long ncRNAs and circular RNAs that are involved in MDR. Thus far, studies have been conducted to identify strategies with which to overcome HMGB1­mediated MDR by the targeted silencing of HMGB1 and the targeted interference of HMGB1 expression using drugs and ncRNAs. Therefore, HMGB1 is closely associated with tumor MDR and is a promising therapeutic target.


Assuntos
Proteína HMGB1 , Neoplasias , Humanos , Proteína HMGB1/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Apoptose/genética , Autofagia/genética , Morte Celular
16.
Int Med Case Rep J ; 16: 245-249, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37066133

RESUMO

Background: Lead poisoning is a rare but serious disease. The clinical manifestations of lead poisoning are various and nonspecific, such as abdominal pain, headache, dizziness, nightmare, fatigue and so on. Rapid diagnosis of lead poisoning is challenging because it does not have special symptoms and the morbidity is very low. Case Presentation: A 31-year-old woman presented with epigastric discomfort without any obvious cause. The patient was diagnosed with lead poisoning, as the blood levels of heavy metals were detected and the lead was 463.17 µg/L, which was very high (normal value was less than 100 µg/L). The patient was treated with intravenous drip of calcium sodium edentate and got better. The patient achieved good recovery and there was no recurrence. Conclusion: Lead poisoning is a rare disease and easy to be misdiagnosed as acute abdomen disease when present with abdominal pain. Lead poisoning should be considered when common causes of abdominal pain are excluded, especially patients with anemia and abnormal liver function. The diagnosis of lead poisoning is mainly replied on the blood or urine lead concentrations. Then we should firstly cut off the contact with lead and use metal complexing agent to facilitate lead excretion.

17.
Phys Chem Chem Phys ; 25(18): 12565-12586, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37102210

RESUMO

Catalyst activity affects the reaction rate, and an increasing number of studies have shown that strain can significantly increase the electrocatalytic activity. Catalysts such as alloys and core-shell structures can modulate their properties through strain effects. Reasonable simulation techniques can be used to predict and design the catalytic performance based on understanding the strain action mechanism. Therefore, the methodological flow of theoretical simulations is summarised in this review. The mechanism underlying the strain-adsorption-reaction relationship is discussed using density functional theory (DFT) calculations. An introduction to DFT is given first, followed by a quick rundown of the strain classification and application. Typical electrocatalytic reactions, namely, the hydrogen and oxygen evolution reactions and oxygen reduction reaction, are taken as examples. After briefly explaining these reactions, the relevant studies on simulating the strain to tune the catalyst performance are covered. The simulation methods are summarised and analysed to observe the effects of strain on electrocatalytic properties. Finally, a summary of the issues with simulated strain-assisted design and a discussion on the perspectives and forecasts for the future design of effective catalysts are provided.

18.
Sci Adv ; 9(2): eadc8845, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36638177

RESUMO

All dielectric materials including ceramics, semiconductors, biomaterials, and polymers have the property of flexoelectricity, which opens a fertile avenue to sensing, actuation, and energy harvesting by a broad range of materials. However, the flexoelectricity of solids is weak at the macroscale. Here, we achieve an ultrahigh flexoelectric effect via a composite foam based on PDMS and CCTO nanoparticles. The mass- and deformability-specific flexoelectricity of the foam exceeds 10,000 times that of the solid matrix under compression, yielding a density-specific equivalent piezoelectric coefficient 120 times that of PZT. The flexoelectricity output remains stable in 1,000,000 deformation cycles, and a portable sample can power LEDs and charge mobile phones and Bluetooth headsets. Our work provides a route to exploiting flexible and light-weight materials with highly sensitive omnidirectional electromechanical coupling that have applications in sensing, actuation, and scalable energy harvesting.

19.
J Gastrointest Oncol ; 13(4): 1746-1752, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092330

RESUMO

Background: For patients with rectal and sigmoid colon cancer, dissecting No. 253 lymph nodes and preserving the left colic artery are the essentials of radical surgery. In clinical work, some surgeons prefer to dissect lymph nodes with skeletonization, believing that lymph nodes can be dissected completely by this method, while other surgeons prefer to dissect lymph nodes with venation. They believe that their method can not only dissect lymph nodes completely but also ensure the safety of patients. This study aimed to investigate whether lymphadenectomy with skeletonization is superior to lymphadenectomy with venation for patients with rectal and sigmoid colon cancer. Methods: We performed a retrospective cohort study between August, 2017 and October, 2019 at the Department of General Surgery, the Affiliated Hospital of Nanjing University Medical School. The inclusion criteria were as follows: diagnosed as rectum or sigmoid colon adenocarcinoma by electronic colonoscopy and histopathology; 18-80 years of age; underwent radical resection. The exclusion criteria were as follows: received neoadjuvant therapy before surgery; combined with distant metastasis. According to the method of lymph node dissection, patients were divided into the skeletonization group and venation group. We then compared the curative effect and safety between the 2 groups. Results: A total of 211 patients were recruited in this retrospective study and assigned as follows: 62 cases to the skeletonization group and 149 patients to the venation group. There were no statistical differences in the total number of lymph nodes (P=0.082), number of positive lymph nodes (P=0.097), total number of No. 253 lymph nodes (P=0.096), number of positive No. 253 lymph nodes (P=0.813), and nodal staging (P=0.254) between the 2 groups. However, the amount of bleeding in the skeletonization group was significantly higher than that in the venation group (P≤0.001), and the operation time in the skeletonization group was also significantly longer than that in the venation group (P≤0.001). Conclusions: Lymphadenectomy with venation is preferred in the radical resection of patients with rectal and sigmoid colon cancer.

20.
Front Pharmacol ; 13: 929901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991871

RESUMO

Postoperative ileus (POI) is a well-known complication following gut manipulation or surgical trauma, leading to an impaired gut motility and prolonged postoperative recovery time. Few current therapeutic strategies can prevent POI, and this disorder remains to be a major clinical challenge for patients undergoing surgery. Comprehensive understanding of cellular and molecular mechanisms related to the pathogenesis of POI stimulates the discovery of more promising targets for treatment. POI is closely associated with a series of inflammatory events within the bowel wall, and as key components of inflammatory mechanisms, different types of immune cells, including macrophages, dendritic cells, and T lymphocytes, play significant roles during the development of POI. A variety of immune cells are recruited into the manipulation sites after surgery, contributing to early inflammatory events or impaired gut motility. Our review intends to summarize the specific relationship between different immune cells and POI, mainly focusing on the relevant mechanisms underlying this disorder.

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