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1.
Infect Agent Cancer ; 19(1): 21, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693556

RESUMO

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

2.
Int J Biol Macromol ; 268(Pt 1): 131699, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642689

RESUMO

Starch and peanut oil (PO) were widely used to improve the gel properties of surimi, however, the impact mechanism of addition forms on the denaturation and aggregation behavior of myofibrillar protein (MP) is not clear. Therefore, the effect of starch, PO, starch/PO mixture, and starch-based emulsion on the physicochemical and gel properties of MP was investigated. The results showed that amylose could accelerate the aggregation of MP, while amylopectin was conducive to the improvement of gel properties. The addition of PO, starch/PO mixture, or starch-based emulsion increased the turbidity, solubility, sulfhydryl content of MP, and improved the gel strength, whiteness, and texture of MP gel. However, compared with starch/PO mixture group, the gel strength of MP with waxy, normal and high amylose corn starch-based emulsion increased by 22.68 %, 10.27 %, and 32.89 %, respectively. The MP containing emulsion had higher storage modulus than MP with starch/PO mixture under the same amylose content. CLSM results indicated that the oil droplets aggregated in PO or starch/PO mixture group, while emulsified oil droplets filled the protein gel network more homogeneously. Therefore, the addition of starch and PO in the form of emulsion could effectively play the filling role to improve the gel properties of MP.

3.
Inorg Chem ; 63(15): 6972-6979, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38567571

RESUMO

Single-crystal membranes (SCMs) show great promise in the fields of sensors, light-emitting diodes, and photodetection. However, the growth of a large-area single-crystal membranes is challenging. We report a new organic-inorganic SCMs [HCMA]2CuBr4 (HCMA = cyclohexanemethylamine) crystallized at the gas-liquid interface. It also has low-temperature ferromagnetic order, high-temperature dielectric anomalies, and narrow band gap indirect semiconductor properties. Specifically, the reversible phase transition of the compound occurs at 350/341 K on cooling/heating and exhibits dielectric anomalies and stable switching performance near the phase transition temperature. The ferromagnetic exchange interaction in the inorganic octahedra and the organic layer enables ferromagnetic ordering at low-temperature 10 K. Finally, the single crystal exhibits an indirect semiconducting property with a narrow band gap of 0.99 eV. Such rich multichannel physical properties make it a potential application in photodetection, information storage and sensors.

4.
Medicine (Baltimore) ; 103(17): e37974, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669376

RESUMO

"Internet + Nursing" refers to medical institutions using Internet technologies and big data to provide nursing services to discharged patients or those with severe illnesses unable to visit hospitals, through online applications and offline care provision. This study aimed to explore the influence of "Internet + Nursing" on the psychological status and quality of life of patients with thyroid eye disease. Sixty-eight patients with thyroid eye disease from January 2021 to December 2022 were divided into a research group (n = 34, joined the platform) and control group (n = 34, not joined the platform) based on their voluntary participation in our hospital's "Internet + Nursing Platform." The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the research group were lower than those of the control group (P < .05). The short form-36 health survey (SF-36) scores in various dimensions were higher in the research group compared to the control group (P < .05). The incidence rates of retinal detachment, vitreous hemorrhage, diabetic retinopathy, and iris neovascularization were lower in the research group compared to the control group (P < .05). After nursing, exophthalmos, blink frequency, and eyelid height of the research group were lower than those of the control group, while tear film breakup time was higher than that of the control group (P < .05). The visual acuity of the research group was higher than that of the control group (P < .05). After nursing, the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) scores in various dimensions were significantly higher in the research group than those in the control group (P < .05). Additionally, after nursing, the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the research group were lower than those in the control group (P < .05). The patients in the research group exhibited higher recognition scores of nursing compared to those in the control group (P < .05). Through the implementation of "Internet + Nursing" for patients with thyroid eye disease discharged from our hospital, we can provide better out-of-hospital nursing for patients, reduce the occurrence of complications, improve ocular surface symptoms, promote visual acuity recovery, and improve patients' psychological status and quality of life.


Assuntos
Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Internet , Oftalmopatia de Graves/psicologia , Idoso
6.
J Hazard Mater ; 469: 133855, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38428296

RESUMO

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 µg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 µg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 µg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.


Assuntos
Aterosclerose , Placa Aterosclerótica , Poluentes Químicos da Água , Humanos , Microplásticos , Plásticos/análise , Pirólise , Artérias/química , Cromatografia Gasosa-Espectrometria de Massas , Poluentes Químicos da Água/química
7.
Blood Cancer J ; 14(1): 38, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38443358

RESUMO

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM.


Assuntos
Mieloma Múltiplo , Paraproteinemias , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Plasmócitos , Prognóstico , Análise de Sequência de RNA , Microambiente Tumoral
8.
iScience ; 27(3): 109277, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455971

RESUMO

Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene TRM-derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall survival and immune activation, particularly in T cell-mediated responses. Altogether, our analysis suggests that TRM abundance is associated with melanoma TIME activation and patient survival, and the TRM-based machine learning model can potentially predict prognosis in melanoma patients.

9.
BJC Rep ; 22024.
Artigo em Inglês | MEDLINE | ID: mdl-38312352

RESUMO

BACKGROUND/OBJECTIVES: Checkpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4. SUBJECTS/METHODS: In this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the hits molecules with biochemical, biophysical, immunological, and experimental animal assays. RESULTS: The primary hits obtained from the virtual screening were successfully validated in vitro and in vivo. We then optimized lead compounds and obtained inhibitors (inhibitory concentration, 1 micromole) that disrupted the CTLA-4/CD80 interaction without degrading CTLA-4. CONCLUSIONS: Several compounds inhibited tumor development prophylactically and therapeutically in syngeneic and CTLA-4-humanized mice. Our findings support using AI-based frameworks to design small molecules targeting immune checkpoints for cancer therapy.

10.
Inorg Chem ; 63(9): 4249-4259, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38364203

RESUMO

The emission of volatile organic compounds (VOCs) significantly contributes to air pollution and poses a serious threat to human health. Benzene, one of the most toxic VOCs, is difficult for the human body to metabolize and is classified as a Group 1 carcinogen. The development of efficient adsorbents for removing trace amounts of benzene from ambient air is thus of great importance. In this work, we studied the benzene adsorption properties of four Zr-based metal-organic frameworks (Zr-MOFs) through static volumetric and dynamic breakthrough experiments. Two previously reported Zr-MOFs, BUT-12 and STA-26, were prepared with a tritopic carboxylic acid ligand (H3L1) functionalized with three methyl groups, and STA-26 is a 2-fold interpenetrated network of BUT-12. Two new isoreticular Zr-MOFs, BUT-12-Et and STA-26-Et, were synthesized using a similar ligand, H3L2, where the methyl groups are replaced with ethyl groups. There are mesopores in BUT-12 and BUT-12-Et and micropores in STA-26 and STA-26-Et. The four Zr-MOFs all showed high stability in liquid water and acidic aqueous solutions. The microporous STA-26 and STA-26-Et showed much higher benzene uptakes than mesoporous BUT-12 and BUT-12-Et at room temperature under low pressures. Particularly, the benzene adsorption capacity of STA-26-Et was high up to 2.21 mmol/g at P/P0 = 0.001 (P0 = 12.78 kPa), higher than those of the other three Zr-MOFs and most reported solid adsorbents. Breakthrough experiments confirmed that STA-26-Et could effectively capture trace benzene (10 ppm) from dry air; however, its benzene capture capacity was reduced by 90% under humid conditions (RH = 50%). Coating of the crystals of STA-26-Et with polydimethylsiloxane (PDMS) increased the hydrophobicity of the exterior MOF surfaces, leading to a more than 2-fold improvement in its benzene capture capacity in the breakthrough experiment under humid condition. PDMS coating of STA-26-Et likely slowed down the water adsorption process, and thus, the adsorbent afforded more efficient capture of benzene. This work demonstrates that modifying both the interior and exterior surfaces of MOFs can effectively enhance their performance in capturing trace benzene from ambient air, even under humid conditions. This finding is meaningful for the development of new adsorbents for effective air purification applications.

11.
Cancer Epidemiol Biomarkers Prev ; 33(3): 389-399, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180474

RESUMO

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Fumantes , Estudo de Associação Genômica Ampla , Projetos de Pesquisa , Fumar/efeitos adversos
12.
Food Funct ; 15(3): 1655-1670, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38251410

RESUMO

The effects of fish oil (FO) and Bacillus subtilis jzxj-7 (JZXJ-7) on the colonic physiology, bacteria, metabolites, and gene expressions were studied in C57BL/6J mice. Co-administration of FO and JZXJ-7 was more beneficial than individual supplementation, as evidenced by improved growth performance, enhanced colon crypt depth and goblet cell numbers. FO + JZXJ-7 inhibited colonic fibrosis by downregulating fibrosis marker protein expression and upregulating occludin, claudin-2 and claudin-4 gene expressions. FO + JZXJ-7 ameliorated oxidative stress and inflammation by increasing catalase, superoxide dismutase, total anti-oxidation capacity, and reducing colon tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 levels. Mechanistically, FO + JZXJ-7 modulated the colon micro-ecological environment by enriching Roseburia, Lachnospiraceae NK4B4, Faecalibaculum and Lactococcus and its derived short-chain fatty acids, and activating Ppara and Car1 mediated peroxisome proliferators-activated receptor (PPAR) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling. Overall, FO + JZXJ-7 may serve as a promising nutraceutical to improve health by boosting the growth of colonic beneficial bacteria, altering metabolic phenotype, and regulating gene expression.


Assuntos
Óleos de Peixe , Microbiota , Camundongos , Animais , Óleos de Peixe/farmacologia , Bacillus subtilis , Fosfatidilinositol 3-Quinases , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa , Perfilação da Expressão Gênica , Metaboloma , Fibrose
13.
Food Chem ; 442: 138369, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38232615

RESUMO

This study investigated the impact of magnetic nanoparticles (MNPs) -assisted cryogenic freezing integrated with MNPs combined microwave thawing (NNMT) on the structural integrity of myofibrillar proteins and alterations in protein profiles in salmon fillets. The NNMT showed the lowest myofibrillar fragmentation index (MFI) value (2.73 ± 0.31) among the four freezing-thawing groups. The myofibrillar structure exhibited the highest level of integrity, while the myofibrillar proteins demonstrated minimal aggregation and displayed the most stable secondary and tertiary structures in response to NNMT treatment. Compared with the other three treatments, NNMT exhibited a high abundance of ionic and hydrogen bonds, resulting in stronger interactions between the proteins and water molecules. The label-free proteomics analysis revealed that different freezing-thawing methods primarily affected the cytoskeletal proteins, with collagen and myosin being down-regulated due to degradation caused by cold stress and recrystallization. Additionally, NNMT demonstrated a superior capability in stabilizing salmon cytoskeletal proteins.


Assuntos
Salmo salar , Animais , Congelamento , Proteômica , Proteínas , Miosinas
14.
Chem Soc Rev ; 53(4): 2056-2098, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38214051

RESUMO

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

15.
J Cell Mol Med ; 28(2): e18067, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38071502

RESUMO

We intend to evaluate the importance of N7 -methylguanosine (m7G) for the prognosis of breast cancer (BC). We gained 29 m7G-related genes from the published literature and among them, 16 m7G-related genes were found to have differential expression. Five differentially expressed genes (CYFIP1, EIF4E, EIF4E3, NCBP1 and WDR4) were linked to overall survival. This suggests that m7G-related genes might be prognostic or therapeutic targets for BC patients. We put the five genes to LASSO regression analysis to create a four-gene signature, including EIF4E, EIF4E3, WDR4 and NCBP1, that divides samples into two risky groups. Survival was drastically worsened in a high-risk group (p < 0.001). The signature's predictive capacity was demonstrated using ROC (10-year AUC 0.689; 10-year AUC 0.615; 3-year AUC 0.602). We found that immune status was significantly different between the two risk groups. In particular, NCBP1 also has a poor prognosis, with higher diagnostic value in ROC. NCBP1 also has different immune states according to its high or low expression. Meanwhile, knockdown of NCBP1 suppresses BC malignancy in vitro. Therefore, m7G RNA regulators are crucial participants in BC and four-gene mRNA levels are important predictors of prognosis. NCBP1 plays a critical target of m7G mechanism in BC.


Assuntos
Neoplasias da Mama , Guanosina , Feminino , Humanos , Biomarcadores , Neoplasias da Mama/genética , Fator de Iniciação 4E em Eucariotos , Proteínas de Ligação ao GTP , Guanosina/análogos & derivados , Complexo Proteico Nuclear de Ligação ao Cap/metabolismo , Prognóstico
16.
Breast J ; 2023: 6282654, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075552

RESUMO

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Apoptose , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células MDA-MB-231 , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Fatores de Transcrição
17.
Drug Des Devel Ther ; 17: 3723-3748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107658

RESUMO

Purpose: This study aimed to investigate the main pharmacological action and underlying mechanisms of Jin Gu Lian Capsule (JGL) against rheumatoid arthritis (RA) based on network pharmacology and experimental verification. Methods: Network pharmacology approaches were performed to explore the core active compounds of JGL, key therapeutic targets, and signaling pathways. Molecular docking was used to predict the binding affinity of compounds with targets. In vivo experiments were undertaken to validate the findings from network analysis. Results: A total of 52 targets were identified as candidate JGL targets for RA. Sixteen ingredients were identified as the core active compounds, including, quercetin, myricetin, salidroside, etc. Interleukin-1 beta (IL1B), transcription factor AP-1 (JUN), growth-regulated alpha protein (CXCL1), C-X-C motif chemokine (CXCL)3, CXCL2, signal transducer and activator of transcription 1 (STAT1), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase (MMP)1, inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and transcription factor p65 (RELA) were obtained as the key therapeutic targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the efficacy of JGL was functionally involved in regulating immune-mediated inflammation, in which IL-17/NF-κB signaling was recommended as one of the main pathways. Molecular docking suggested that the core active compounds bound strongly to their respective targets. Experimentally, JGL treatment mitigated inflammation, showed analgesic activity, and ameliorated collagen-induced arthritis. Enzyme-linked immunosorbent assay showed that JGL effectively reduced the serum levels of cytokines, chemokines, and MMPs. Immunohistochemistry staining showed that JGL markedly reduced the expression of the targets in IL-17/NF-κB pathway including IL-17A, IL-17RA, NF-κB p65, C-X-C motif ligand 2, MMP1 and MMP13. Conclusion: This investigation provided evidence that JGL may alleviate RA symptoms by partially inhibiting the immune-mediated inflammation via IL-17/NF-κB pathway.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Humanos , NF-kappa B , Fator de Transcrição RelA , Interleucina-17 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia
18.
Transl Cancer Res ; 12(10): 2875-2886, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969381

RESUMO

Background: To identify differently expressed circular RNA (circRNA) in oral squamous cell carcinoma (OSCC) and adjacent normal tissue, construct a hsa_circ_0112879-related microRNAs (miRNAs) prognostic model, and discuss the circRNA as a biomarker for early diagnosis of OSCC. Methods: The expression of hsa_circ_0112879 in OSCC cell lines and tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to estimate its clinical significance. The potential miRNA and messenger RNA (mRNA) binding to hsa_circ_009755 were predicted by R software edgeR package. Based on the median value of the risk score in the all-sample cohort, all the included patients with OSCC were divided into either high- or low-risk groups, and Kaplan-Meier analysis was performed. The ROC curve was used to verify the accuracy of the risk signature in predicting the prognosis of OSCC. By univariable Cox, least absolute shrinkage and selection operator (LASSO), and multivariable Cox analyses, we constructed a hsa_circ_0112879-related miRNAs risk model to forecast the prognosis of OSCC. Results: The expression of hsa_circ_0112879 was significantly downregulated in the OSCC tissues and cell lines. The expression level was statistically correlated with the pathological differentiation of OSCC tumors (P=0.0285). Furthermore, 141 differentially expressed hsa_circ_0112879-related miRNAs were obtained [|log2FC| >1, false discovery rate (FDR) <0.05], of which 70 miRNAs were up-regulated in OSCC tissues, whereas 71 miRNAs were down-regulated in OSCC tissues. The area under the ROC curve (AUC) at 1-, 3-, and 5-year in the all-sample cohort was 0.591, 0.689, and 0.618, respectively. The toll-like receptor signaling pathway, Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway, and T-cell receptor (TCR) signaling pathway were mainly enriched in the high-risk group. Conclusions: The model and nomogram constructed herein has the ability to discriminate the prognosis of OSCC patients. Hsa_circ_0112879 may serve as a novel biomarker in the diagnosis and prognosis of OSCC.

19.
J Surg Case Rep ; 2023(11): rjad610, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37965538

RESUMO

Patients with hepatocellular carcinoma at high risk of recurrence after hepatic resection or local ablation often undergo adjuvant immunotherapy with immune checkpoint inhibitors for 1 year in randomized controlled trials, but the appropriateness of this duration is controversial, especially given the risk of adverse events. Here we report the case of a 52-year-old Chinese man with initially unresectable multinodular recurrent hepatocellular carcinoma who underwent two cycles of transarterial chemoembolization, followed by hepatic resection and 24 months of adjuvant therapy with the PD-1 inhibitor tislelizumab. The patient achieved a recurrence-free survival time of 24 months, but he experienced elevated alpha fetoprotein, Grade 2 hypothyroidism and pruritus while on adjuvant therapy. This case highlights the need to optimize the duration of adjuvant immunotherapy after curative treatment for hepatocellular carcinoma in order to minimize risk of not only recurrence but also adverse events.

20.
Polymers (Basel) ; 15(18)2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37765582

RESUMO

Polybutene-1 with form I crystals exhibits excellent creep resistance and environmental stress crack resistance. The filaments of polybutene-1 and its random copolymer with 4 mol% ethylene co-units were produced via extrusion melt spinning, which are expected to be in form I states and show outstanding mechanical properties. The variances in microstructure, crystallization-melting behavior, and mechanical properties between homopolymer and copolymer filaments were analyzed using SEM, SAXS/WAXD, DSC, and tensile tests. The crystallization of form II and subsequent phase transition into form I finished after the melt-spinning process in the copolymer sample while small amounts of form II crystals remained in homopolymer filaments. Surprisingly, copolymer filaments exhibited higher tensile strength and Young's modulus than homopolymer filaments, while the homopolymer films showed better mechanical properties than copolymer films. The high degree of orientation and long fibrous crystals play a critical role in the superior properties of copolymer filaments. The results indicate that the existence of ethylene increases the chain flexibility and benefits the formation of intercrystalline links during spinning, which contributes to an enhancement of mechanical properties. The structure-property correlation of melt-spun PB-1 filaments provides a reference for the development of polymer fibers with excellent creep resistance.

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