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1.
J Sci Food Agric ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39243159

ABSTRACT

BACKGROUND: Rhamnolipids (RLS) are surfactants that improve the growth performance of poultry by improving the absorption of nutrients. This study aims to investigate the effects of RLS replacement of chlortetracycline (CTC) on growth performance, slaughtering traits, meat quality, antioxidant function and nuclear-factor-E2-related factor 2 (Nrf2) signaling pathway in broilers. A total of 600 one-day-old Arbor Acres chicks were randomly assigned to five groups with eight replicates in each group, raised for 42 days. Broilers were respectively fed a basal diet with no CTC or RLS, 75 mg kg-1 CTC, and 250, 500, 1000 mg kg-1 RLS. RESULTS: Dietary supplementation with RLS linearly increased the average daily gain, average daily feed intake, carcass yield, eviscerated yield, ether extract, enhanced total superoxide and glutathione peroxidase (GPx) activities, overexpressed the relative expressions of Nrf2, heme oxygenase 1, Copper/zinc superoxide dismutase, Manganese superoxide dismutase, GPx and catalase and decreased the lightness value at 24 h, drip loss and malondialdehyde contents of broilers (P < 0.05). Compared with the control group, broilers fed 1000 mg kg-1 RLS reduced the drip loss and broilers fed 500 mg kg-1 RLS increased muscle crude fat content (P < 0.05). Compared with the CTC group, dietary supplementation with 1000 mg kg-1 RLS increased eviscerated yield (P < 0.05). CONCLUSION: RLS could improve growth performance, crude fat content, meat quality and antioxidant capacity and activate relative expression of genes in the Nrf2 signaling pathway in broilers. It could be used as an antibiotic substitute in diets and the recommended supplemental dose of RLS in feed of broilers is 1000 mg kg-1. © 2024 Society of Chemical Industry.

2.
Chin Med ; 19(1): 129, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39289763

ABSTRACT

BACKGROUND: Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients' quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear. OBJECTIVE: To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components. METHODS: We constructed an antitumor pCm database based on China's medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC. RESULTS: The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods. CONCLUSION: Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.

3.
Light Sci Appl ; 13(1): 262, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39300089

ABSTRACT

Conventional dielectric solid materials, both natural and artificial, lack electromagnetic self-duality and thus require additional coatings to achieve impedance matching with free space. Here, we present a class of dielectric metamaterials that are effectively self-dual and vacuum-like, thereby exhibiting full-polarization omnidirectional impedance matching as an unusual Brewster effect extended across all incident angles and polarizations. With both birefringence and reflection eliminated regardless of wavefront and polarization, such anisotropic metamaterials could establish the electromagnetic equivalence with "stretched free space" in transformation optics, as substantiated through full-wave simulations and microwave experiments. Our findings open a practical pathway for realizing unprecedented polarization-independence and omnidirectional impedance-matching characteristics in pure dielectric solids.

4.
Chembiochem ; : e202400669, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39304987

ABSTRACT

Nucleic acid strand displacement is a pivotal concept in dynamic nucleic acid nanotechnologies, which has been extensively investigated and applied across various fields. Compared with DNA systems, the genetically expressed RNA strand displacement technology offers unique advantages for construction of genetic circuits in living cells, where RNA expression and modulation may be seamlessly integrated into the genomic network for long-term and stable regulations of diversified biological functionalities. This Concept paper provides an overview of previous efforts on developments of synthetic gene circuits through utilization of RNA strand displacement, including our endeavors in this field. Moreover, future prospects, potential applications and challenges of the genetically expressed RNA strand displacement technology are also discussed.

5.
Nat Commun ; 15(1): 8130, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285201

ABSTRACT

Allosteric drugs offer a new avenue for modern drug design. However, the identification of cryptic allosteric sites presents a formidable challenge. Following the allostery nature of residue-driven conformation transition, we propose a state-of-the-art computational pipeline by developing a residue-intuitive hybrid machine learning (RHML) model coupled with molecular dynamics (MD) simulation, through which we can efficiently identify the allosteric site and allosteric modulator as well as reveal their regulation mechanism. For the clinical target ß2-adrenoceptor (ß2AR), we discover an additional allosteric site located around residues D792.50, F2826.44, N3187.45 and S3197.46 and one putative allosteric modulator ZINC5042. Using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and protein structure network (PSN), the allosteric potency and regulation mechanism are probed to further improve identification accuracy. Benefiting from sufficient computational evidence, the experimental assays then validate our predicted allosteric site, negative allosteric potency and regulation pathway, showcasing the effectiveness of the identification pipeline in practice. We expect that it will be applicable to other target proteins.


Subject(s)
Allosteric Site , Machine Learning , Receptors, Adrenergic, beta-2 , Humans , Allosteric Regulation , Drug Design , Molecular Dynamics Simulation , Protein Conformation , Receptors, Adrenergic, beta-2/chemistry , Receptors, Adrenergic, beta-2/metabolism
6.
J Agric Food Chem ; 72(37): 20273-20285, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39226040

ABSTRACT

Transposon mutagenesis screening of Bacillus subtilis YB-1471, a novel rhizosphere biocontrol agent of Fusarium crown rot (FCR) of wheat, resulted in the identification of orf04391, linked to reduced biofilm formation. The gene encodes a protein possessing a putative tertiary structure of a "double-wing" DNA-binding domain. Expression of orf04391 increased during biofilm development in stationary cultures and during rapid growth in shaking cultures. An orf04391 deletion strain showed reduced biofilm production related to lower levels of the extracellular matrix, and the mutant also had reduced sporulation, adhesion, root colonization, and FCR biocontrol efficiency. Transcriptome analysis of YB-1471 and Δorf04391 in stationary culture showed that the loss of orf04391 resulted in altered expression of numerous genes, including sinI, an initiator of biofilm formation. DNA binding was shown with his-tagged Orf04391 binding to the sinIR operon in vivo and in vitro. Orf04391 appears to be a transcriptional regulator of biofilm formation in B. subtilis through the Spo0A-SinI/SinR pathway.


Subject(s)
Bacillus subtilis , Bacterial Proteins , Fusarium , Plant Diseases , Triticum , Bacillus subtilis/genetics , Bacillus subtilis/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Biofilms/growth & development , Fusarium/genetics , Fusarium/metabolism , Fusarium/physiology , Gene Expression Regulation, Bacterial , Plant Diseases/microbiology , Triticum/microbiology
7.
J Med Chem ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39312756

ABSTRACT

Chemoresistance remains an arduous challenge in oncology, but ferroptosis shows potential for overcoming it by stimulating the immune system. Herein, a novel high-performance ruthenium(II)-based arene complex [Ru(η6-p-cym)(BTBpy)Cl] (RuBTB) is developed for ferroptosis-enhanced antitumor immunity and drug resistance reversal via glutathione (GSH) metabolism imbalance. RuBTB shows significantly enhanced antiproliferation activity against cisplatin (CDDP)-resistant lung cancer cells (A549R), with 26.35-fold better anticancer effects than CDDP. Immunogenic ferroptosis is induced by GSH depletion/glutathione peroxidase 4 (GPX4) inactivation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in RuBTB-treated cells. Mechanism studies indicate that RuBTB regulates ferroptosis and immune-related pathways, coordinating with GSH metabolism-mediated glutathione S-transferase (GST) inhibition to reverse drug resistance in platinum-combined therapy. Tumor vaccination experiments demonstrate the intensified antitumor effects endowed by highly immunogenic ferroptosis in vivo. This study provides the first example of a metal-arene complex for achieving satisfactory ferroptosis therapeutic effects with efficient immunogenicity to overcome drug resistance in metal-based immunochemotherapy.

8.
Br J Dev Psychol ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39315748

ABSTRACT

Source monitoring (SM) refers to attributing sources of information. There are various methods for measuring SM in children. We searched the PubMed, PsycINFO, Embase, Web of Science and Cochrane Library databases from their inception to February 24, 2023, to summarize the methods and measures of SM in children, identifying 141 studies. The procedure for the SM tasks encompassed encoding, interval and testing. The encoding tasks were classified into ground-based activities (n = 67), computer-based experiments (n = 42) and mixed methods (n = 34). The testing approaches were categorized into old/new recognition and source discrimination, n-alternative forced-choice, yes/no questions and recall/direct questions. Among 10 commonly used indicators, source-correct, source-incorrect, discrimination score and source accuracy were recommended to present the SM function. We also discussed the advantages and disadvantages of different SM methods in children, providing a reference for researchers to design and select SM measurements that meet their research objectives.

9.
J Am Chem Soc ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39263868

ABSTRACT

Electrochemical CO2 reduction (CO2R) in acidic media provides a pathway to curtail CO2 losses by suppressing the formation of (bi)carbonates. In such systems, a high concentration of alkali metal cations is necessary for mitigating the proton-rich environment and suppressing the competing hydrogen evolution reaction. However, a high cation concentration also promotes salt precipitation within the gas diffusion layer, resulting in poor system durability. Here, we resolve this conundrum by replacing the liquid catholyte with a solid-state proton conductor to regulate H+ transport. This is postulated to allow for a locally alkaline environment at the cathode, enabling selective CO2R even without alkali metal cations. We show that this strategy is effective over a broad range of catalyst systems. For instance, we achieve an 87% CO faradaic efficiency (FE) at 300 mA/cm2 using a composite nanoporous Au and single-atom Ni catalyst, with 0.25 M H2SO4 as the anolyte. Stable operation over 110 h and a high single-pass carbon efficiency of 82.8% were also successfully demonstrated. Importantly, we find that this solid-state system is also particularly effective at converting dilute feedstock (5% CO2) with a CO FE of 47.7%, a factor of 16.4 times higher than a conventional system. Our results introduce a simple yet effective design approach for developing efficient acidic CO2R electrolyzers.

10.
Article in English | MEDLINE | ID: mdl-39263882

ABSTRACT

OBJECT: This study aims to explore the clinical and pathologic characteristics of HPV-related primary thyroid squamous cell carcinoma (PSCCT), a rare tumor classified by WHO-5 as a subtype of anaplastic thyroid carcinoma (ATC). METHODS: Clinical data, histomorphology, immunohistochemistry, HPV detection, and B-raf gene point mutations of 3 PSCCT cases were analyzed. Subsequent follow-up was conducted post-treatment. RESULTS: All 3 cases involved female patients aged between 60 and 76. Microscopic examination revealed squamous cell carcinoma in cases 1 and 3, whereas case 2 exhibited both squamous cell carcinoma and papillary thyroid carcinoma components. Immunohistochemistry demonstrated CK19, PAX8, and TTF1 expression in the papillary thyroid carcinoma component, and CK5/6, p63, p40, and PAX8 expression in the squamous cell carcinoma component. P16 exhibited diffuse positivity in both squamous cell carcinoma and classic papillary carcinoma. HPV analysis identified low-risk type 6 positivity in cases 1 and 3, while both squamous cell carcinoma and papillary carcinoma areas in case 2 were positive for HPV-33. B-raf gene mutation was exclusive to case 2. CONCLUSION: Diagnosis of PSCCT necessitates multidisciplinary assessment, incorporating clinical symptoms, imaging, histomorphology, and immunohistochemistry. This study, for the first time, reveals the presence of HPV DNA in both PTC and PSCCT, occurring concurrently but separately. Given the limited scope of 3 case reports, definitive conclusions cannot be drawn, warranting further investigation.

11.
Nurse Educ Pract ; 80: 104145, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39317090

ABSTRACT

AIM: To construct learning objectives and educational content for emergency triage nurses based on core competencies. BACKGROUND: The core competencies of emergency triage nurses has an impact on the quality of medical services and patient treatment outcomes. However, research on learning objectives and educational content aimed at cultivating the core competencies of emergency triage nurses is limited. DESIGN: A Delphi study. METHODS: To develop a draft of the teaching objectives and content for emergency triage nurses based on core competencies, a literature review, semistructured interviews and expert group meetings were conducted. Then, 24 experts were invited to provide feedback on the draft and suggest revisions through two rounds of Delphi consultation. RESULTS: Consensus was reached on six core competencies, 30 learning objectives and 43 educational contents. The response rate for the two rounds of expert questionnaires was 100 %, with 79.2 % and 54.2 % of the experts providing feedback in the first and second rounds, respectively. The judgement coefficient (Ca) was 0.910, the familiarity coefficient (Cs) was 0.917 and the authority coefficient (Cr) was 0.914. The Kendall's W coefficients for the two rounds of expert inquiry were 0.321 and 0.334, indicating a statistically significant difference (P<0.05). CONCLUSIONS: Constructing learning objectives and educational content for emergency triage nurses based on core competencies is scientific and reliable and can provide a reference for the training and management of emergency triage nurses.

12.
Histol Histopathol ; : 18804, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39319525

ABSTRACT

Laryngeal carcinoma (LC) is the second most common malignancy of the head and neck worldwide, with increasing incidence every year. However, the mechanism of its development is not completely clear. Periostin (POSTN) has been reported to be involved in various aspects of tumorigenesis. To determine the influence of POSTN on LC tumorigenesis, we first examined the expression of POSTN in tissues from patients with LC through immunohistochemistry, western blot, and qRT-PCR. Besides, we demonstrated that POSTN promoted LC cell migration, invasion, and proliferation in vitro by CCK-8, colony formation, and Transwell assays, and tumor growth in vivo by immunohistochemistry. Furthermore, the interaction between POSTN and decorin (DCN) was further verified by bioinformatics analysis and immunoprecipitation (IP), finding that POSTN promoted the malignant progression of LC by targeting DCN. Our findings support the idea that the level of POSTN expression and accumulation in tumors correlated with the malignancy degree of LC, suggesting that POSTN may play a potential role in improving laryngeal cancer treatment strategies.

13.
Cell Death Discov ; 10(1): 404, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285178

ABSTRACT

Radiotherapy (RT) is a crucial treatment for colorectal cancer (CRC) patients, but it often fails to induce systemic antitumor immunity. CD73, an immunomodulatory factor, is upregulated after RT and associated with poor prognosis in CRC patients. This study aims to elucidate the mechanisms driving RT-induced CD73 upregulation in CRC and investigate how combining RT with CD73 blockade stimulates immune responses and induces abscopal effects. Findings revealed that RT-induced CD73 upregulation is mediated by the ataxia telangiectasia and Rad3-related (ATR) pathway and correlated with RT tolerance, as demonstrated through flow cytometry, immunofluorescence, and Western Blotting. Using flow cytometry and multicolor immunofluorescence, experiments demonstrated that in CRC subcutaneous tumor models, combination therapy reduces the infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) while increasing dendritic cells (DCs) and CD8 + T cells, resulting in superior antitumor responses. Additionally, results from flow cytometry, Western Blot, and RNA sequencing demonstrated that combination therapy enhances the antigen-presenting ability of DCs and activates tumor antigen-specific CD8 + T cells, improving their function and delaying their depletion. The activation of the cGAS-STING and IFN-I pathways is crucial for this effect. In summary, the integration of RT with CD73 blockade effectively reverses the immunosuppressive TME and invigorates CD8 + T cell-driven, specific antitumor immune responses. These insights shed fresh light on the mechanisms governing the synergistic modulation of immunity by RT and CD73 blockade in CRC, offering promising avenues for the advancement of therapeutic strategies against CRC.

14.
Sci Total Environ ; 954: 176171, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260497

ABSTRACT

Carbon dioxide (CO2) serves as a crucial greenhouse gas that traps heat and regulates the Earth's temperature. High spatiotemporal resolution CO2 estimation can provide valuable information to understand the characteristics of fine-scale climate change trends and to formulate more effective emission reduction strategies. This study presents a spatiotemporal ResNet model (ST-ResNet) specifically developed to estimate the highest resolution (1 km × 1 km) daily column-averaged dry-air mole fraction of CO2 (XCO2) in China from 2015 to 2020. The ST-ResNet model excels in estimating XCO2 by comprehensively considering the complex relationships between XCO2 and its various influencing factors, while efficiently capturing both temporal and spatial correlations, thereby demonstrating remarkable generalization capability. The results show that the ST-ResNet generates a highly accurate XCO2 dataset, outperforming the traditional ResNet. Ground-based validation results further confirm the high accuracy and spatiotemporal resolution of our estimated data product. Using this dataset, the spatial and temporal characteristics of XCO2 across the entire China and several urban agglomerations have been analyzed. The high spatiotemporal resolution estimated XCO2 dataset for China is made publicly available at [https://doi.org/10.6084/m9.figshare.25272868], offering substantial potential for fine-scale carbon research.

15.
BJS Open ; 8(5)2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39325149

ABSTRACT

BACKGROUND: The 'Learn, See, Practice, Prove, Do, Maintain' (LSPPDM) pedagogical framework is an evidence-based framework developed through a careful review and synthesis of the literature. The purpose of the study was to explore the effectiveness and applicability of the LSPPDM pedagogical framework in the laparoscopic training course for surgical residents. METHODS: Prospective study of surgical residents who underwent standardized surgical residency training in a single institution from December 2020 to December 2022. Trainees were randomized to either the pedagogical group (6-step LSPPDM pedagogical framework) or traditional group (2-step traditional approach with twice-weekly lectures and a weekly laparoscopic operating skills session). The Global Operative Assessment of Laparoscopic Skills scale was used for technical skills, and the Non-Technical Skills for Surgeons assessment form was used for non-technical skills. RESULTS: Sixty trainees were randomized. The pedagogical group scored higher on subjective perception (P < 0.050) and the theoretical assessment (mean(s.d.) 41.83(6.66)) than those in the traditional group (37.83(5.77)) (P = 0.016). Trainees in the pedagogical group took less time to complete the assessment of models, had fewer failures and higher scores, took less time to complete laparoscopic sutures and knots, showed better proficiency with laparoscopic instruments, and completed at higher quality (P < 0.050). Trainees performing laparoscopic cholecystectomy in animal models demonstrated higher technical and non-technical skill scores in the pedagogical group (P < 0.050). 'Tissue handling' and 'Decision making' were common areas for improvement for both groups of trainees. CONCLUSIONS: The LSPPDM pedagogical framework is feasible and demonstrated improvements in technical and non-technical skills in surgical trainees compared to a traditional training programme.


Subject(s)
Clinical Competence , Internship and Residency , Laparoscopy , Humans , Laparoscopy/education , Prospective Studies , Female , Male , Adult , Curriculum , Education, Medical, Graduate/methods
16.
Infect Genet Evol ; 125: 105669, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39299538

ABSTRACT

OBJECTIVE: This study aims to analyze the genomic and clinical characteristics of Non-baumannii Acinetobacter strains misidentified as A. baumannii, causing bloodstream infections (BSIs) in our hospital. MATERIALS AND METHODS: Whole genome sequencing was performed and average nucleotide identity (ANI) was analyzed. Susceptibility testing was conducted using micro-broth methods. The distribution of antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) was examined using online software tools. The prevalence of virulence factors (VFs) was investigated through nucleotide coding sequence comparisons. Genetic structures of blaOXA genes were analyzed by Gcluster software. Clinical information was collected from electronic medical records for patient characterization. RESULTS: ANI analysis identified five strains as Acinetobacter pittii, with the remaining four identified as A. geminorum, A. nosocomialis, A. soli and A. bereziniae. The GC content of all isolates was less than 38.9 % except for A. soli 16,294. All Non-baumannii Acinetobacter strains were relatively susceptible to antibiotics, except for one A. pittii isolate. Nine blaOXA variants were identified in seven isolates, with two isolates co-carrying 2 different types of blaOXA. Twenty-four insertion sequences (ISs) were identified, with ISAba and IS17 being the primary ISs. Five A. pittii isolates shared the same genetic structures around blaOXA. Genes related to adherence, immune modulation, and nutritional/metabolic factors were the most frequent. Few VFs were detected in A. soli 16,294 and A.bereziniae 14,325. CONCLUSIONS: The presence of carbapenem hydrolyzing oxacillinase encoding genes did not confer carbapenem resistance, possibly due to the lack of ISs in the blaOXA flanking sequences. Different blaOXA variants within distinct strains shared the same genetic structures, suggesting potential for multidrug resistance development, which warrants our attention.

17.
Article in English | MEDLINE | ID: mdl-39324518

ABSTRACT

Aging can impact emotional recognition, affecting older adults' mental health and social function. This study examined how aging affects affective prosody comprehension (APC: understanding emotions through speech) across seven emotions (happiness, surprise, sadness, anger, fear, disgust, and neutrality) and its relationship with cognitive function (via the Montreal Cognitive Assessment) and social support (via the Social Support Rating Scale) in 199 cognitively normal older adults. We found that older adults had lower APC accuracy and more errors, often mistaking negative emotions for neutral or positive ones. APC accuracy was significantly associated with social support, and a partial least squares (PLS) cognitive component fully mediated the relationship between the APC component and social support utilization, explaining 61.7% of the total effect. These results suggest that declines in APC during aging are linked to social support utilization through cognitive function, offering insights for interventions to improve social and cognitive health in older adults.

18.
J Org Chem ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39298438

ABSTRACT

A highly effective external photocatalyst- and additive-free method for the phosphorylation of 3,4-dihydroquinoxalin-2(1H)-ones to produce phosphorylated dihydroquinoxalin-2(1H)-ones has been reported. A wide variety of phosphorylated products were formed in good to excellent yields. Preliminary mechanistic studies reveal that the phosphorylation process involves an EnT process, a SET process, a HAT process, and a deprotonation process.

19.
J Cancer Res Clin Oncol ; 150(9): 429, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39311951

ABSTRACT

BACKGROUND: Ferroptosis, a novel iron-ion-dependent metabolic cell death mode with lipid peroxides as the main driving substrate, plays an irreplaceable role in the development and preventive treatment of hepatocellular carcinoma. Curcumin has potent pharmacological anti-tumor effects. AIM OF THE STUDY: We aimed to evaluate the ex vivo and in vivo cancer inhibitory activity of curcumin and its specific mechanism of action. MATERIALS AND METHODS: We used the hepatocellular carcinoma cell lines HepG2 and SMMC7721 to assess the direct inhibition of hepatocellular carcinoma proliferation by curcumin in vitro and a tumor xenograft model to evaluate the in vivo cancer inhibitory effect of curcumin. RESULTS: In this study, we found that ferroptosis's inhibitors specifically reversed the curcumin-induced cell death pattern in HCC. After curcumin intervention, there was a substantial increase in MDA levels and iron ion levels, and a decrease in intracellular GSH levels. Meanwhile, the expression of GPX4 and SLC7A11 was significantly reduced at the protein levels, while ACSL4 and PTGS2 expression was significantly increased. CONCLUSIONS: This study showed that curcumin significantly decreased the proliferation of HCC cells and significantly increased the sensitivity of ferroptosis. These results suggest that ACSL4 is a viable target for curcumin-induced ferroptosis in treating HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Coenzyme A Ligases , Curcumin , Ferroptosis , Liver Neoplasms , Up-Regulation , Xenograft Model Antitumor Assays , Ferroptosis/drug effects , Curcumin/pharmacology , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Animals , Mice , Coenzyme A Ligases/metabolism , Up-Regulation/drug effects , Cell Proliferation/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Mice, Nude , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Hep G2 Cells , Cell Line, Tumor , Mice, Inbred BALB C , Male , Gene Expression Regulation, Neoplastic/drug effects
20.
Virulence ; 15(1): 2404965, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39317345

ABSTRACT

Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.


Subject(s)
Antiviral Agents , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B, Chronic , Interferon-alpha , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/virology , Hepatitis B, Chronic/blood , Hepatitis B Surface Antigens/blood , Hepatitis B Surface Antigens/immunology , Male , Female , Adult , Retrospective Studies , Hepatitis B Antibodies/blood , Antiviral Agents/therapeutic use , Middle Aged , Hepatitis B e Antigens/blood , Interferon-alpha/therapeutic use , Hepatitis B virus/immunology , Hepatitis B Core Antigens/immunology , Hepatitis B Core Antigens/blood , Treatment Outcome , Drug Therapy, Combination , Seroconversion , Young Adult , Polyethylene Glycols/therapeutic use , Recombinant Proteins/therapeutic use , Recombinant Proteins/immunology
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