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1.
Nat Rev Cancer ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39354069

ABSTRACT

The term 'precancer' typically refers to an early stage of neoplastic development that is distinguishable from normal tissue owing to molecular and phenotypic alterations, resulting in abnormal cells that are at least partially self-sustaining and function outside of normal cellular cues that constrain cell proliferation and survival. Although such cells are often histologically distinct from both the corresponding normal and invasive cancer cells of the same tissue origin, defining precancer remains a challenge for both the research and clinical communities. Once sufficient molecular and phenotypic changes have occurred in the precancer, the tissue is identified as a 'cancer' by a histopathologist. While even diagnosing cancer can at times be challenging, the determination of invasive cancer is generally less ambiguous and suggests a high likelihood of and potential for metastatic disease. The 'hallmarks of cancer' set out the fundamental organizing principles of malignant transformation but exactly how many of these hallmarks and in what configuration they define precancer has not been clearly and consistently determined. In this Expert Recommendation, we provide a starting point for a conceptual framework for defining precancer, which is based on molecular, pathological, clinical and epidemiological criteria, with the goal of advancing our understanding of the initial changes that occur and opportunities to intervene at the earliest possible time point.

3.
Angew Chem Int Ed Engl ; : e202411440, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261286

ABSTRACT

Metal-organic framework (MOF)-based membranes excel in molecular separation, attracting significant research interest. The crystallographic microstructure and selective adsorption capacity of MOFs closely correlate with their gas separation performance. Here, aniline was added to the ZIF-8 synthesis in varying concentrations. Aniline, encapsulated within ZIF-8 cavities, interacts strongly with the 2-methylimidazole linker, resulting in both a shift in crystallographic phase from I_43m to Cm in Rietveld refinement of X-ray diffraction (XRD) patterns and the selective adsorption behavior between propylene and propane. Consequently, an aniline decorative ZIF-8 (Anix-ZIF-8) membrane was prepared using a fast current-driven synthesis method, which exhibits good propylene/propane separation selectivity of up to 85. Calculation of the interaction energy between aniline and the various crystallographic phases of ZIF-8 using density functional theory (DFT) further verifies that aniline not only promotes the formation of crystallographic Cm phase, but also enhances the adsorption selectivity of propylene over propane. Aniline modification effectively tunes the crystallographic microstructure of ZIF-8, thereby, improving molecular sieving capabilities.

4.
Food Chem ; 463(Pt 2): 141162, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39265304

ABSTRACT

The extraction methods for antimicrobial peptides (AMPs) from plants are varied, but the absence of a standardized and rapid technique remains a challenge. In this study, a functionalized biochar was developed and characterized for the extraction of AMPs from pea protein hydrolysates. The results indicated that the biochar mainly enriched AMPs through electrostatic interaction, hydrogen bonding and pore filling. Then three novel cationic antimicrobial peptides were identified, among which the RDLFK (Arg-Asp-Leu-Phe-Lys) had the greatest inhibitory effect against Staphylococcus aureus and Bacillus subtilis, showcasing IC50 value of 2.372 and 1.000 mg/mL, respectively. Additionally, it was found that RDLFK could damage bacterial cell membranes and penetrate the cells to inhibit DNA synthesis. These results provided that the biochar-based extraction method presents an efficient and promising avenue for isolating AMPs, addressing a critical gap in the current methodologies for their extraction from plant sources.

5.
J Neurooncol ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39266885

ABSTRACT

PURPOSE: Improved outcomes have been noted in patients undergoing malignant brain tumor resection at high-volume centers. Studies have arbitrarily chosen high-volume dichotomous cutoffs and have not evaluated volume-outcome associations at specific institutional procedural volumes. We sought to establish the continuous association of volume with patient outcomes and identify cutoffs significantly associated with mortality, major complications, and readmissions. We hypothesized that a linear volume-outcome relationship can estimate likelihood of adverse outcomes when comparing any two volumes. METHODS: The patient cohort was identified with ICD-10 coding in the Nationwide Readmissions Database(NRD). The association of volume and mortality, major complications, and 30-/90-day readmissions were evaluated in multivariate analyses. Volume was used as a continuous variable with two/three-piece splines, with various knot positions to reflect the best model performance, based on the Quasi Information Criterion(QIC). RESULTS: From 2016 to 2018, 34,486 patients with malignant brain tumors underwent resection. When volume was analyzed as a continuous variable, mortality risk decreased at a steady rate of OR 0.988 per each additional procedure increase for hospitals with 1-65 cases/year(95% CI 0.982-0.993, p < 0.0001). Risk of major complications decreased from 1 to 41 cases/year(OR 0.983, 95% CI 0.979-0.988, p < 0.0001), 30-day readmissions from 1 to 24 cases/year(OR 0.987, 95% CI 0.979-0.995, p = 0.001) and 90-day readmissions from 1 to 23 cases/year(OR 0.989, 95% CI 0.983-0.995, p = 0.0003) and 24-349 cases/year(OR 0.9994, 95% CI 0.999-1, p = 0.01). CONCLUSION: In multivariate analyses, institutional procedural volume remains linearly associated with mortality, major complications, and 30-/90-day readmission up to specific cutoffs. The resulting linear association can be used to calculate relative likelihood of adverse outcomes between any two volumes.

6.
Sci Rep ; 14(1): 21915, 2024 09 19.
Article in English | MEDLINE | ID: mdl-39300183

ABSTRACT

Therapy targeting the BRAF-MEK cascade created a treatment revolution for patients with BRAF mutant advanced melanoma. Unfortunately, 80% patients treated will progress by 5 years follow-up. Thus, it is imperative we study mechanisms of melanoma progression and therapeutic resistance. We created a scRNA (single cell RNA) atlas of 128,230 cells from 18 tumors across the treatment spectrum, discovering melanoma cells clustered strongly by transcriptome profiles of patients of origins. Our cell-level investigation revealed gains of 1q and 7q as likely early clonal events in metastatic melanomas. By comparing patient tumors and their derivative cell lines, we observed that PD1 responsive tumor fraction disappears when cells are propagated in vitro. We further established three anti-BRAF-MEK treatment resistant cell lines using three BRAF mutant tumors. ALDOA and PGK1 were found to be highly expressed in treatment resistant cell populations and metformin was effective in targeting the resistant cells. Our study suggests that the investigation of patient tumors and their derivative lines is essential for understanding disease progression, treatment response and resistance.


Subject(s)
Drug Resistance, Neoplasm , Melanoma , Proto-Oncogene Proteins B-raf , Single-Cell Analysis , Humans , Melanoma/drug therapy , Melanoma/genetics , Melanoma/pathology , Melanoma/metabolism , Drug Resistance, Neoplasm/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Cell Line, Tumor , Phosphoglycerate Kinase/genetics , Phosphoglycerate Kinase/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Transcriptome , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Mutation , Metformin/pharmacology , Metformin/therapeutic use
7.
Patient Prefer Adherence ; 18: 2007-2017, 2024.
Article in English | MEDLINE | ID: mdl-39345758

ABSTRACT

Objective: The objective of this study is to systematically explore and summarize the best evidence on intervention programs for patients with kinesophobia following percutaneous coronary intervention (PCI) to provide a comprehensive reference for clinical practice interventions. Methods: Evidence on interventions for kinesophobia post-PCI was retrieved from Chinese and international integrated databases, treatment guidelines, and websites of professional associations, including systematic reviews and expert consensuses. The evidence considered in this study extends up to May 2022, encompassing information available since the inception of the databases. Two researchers independently evaluated the articles included in the review and extracted and summarized the available evidence. Results: By extracting and integrating data from the 14 articles included in this review, we identified six categories: pre-intervention assessment, psychological intervention, health education, rehabilitation training, social support, and quality control. A total of 21 pieces of evidence were summarized, including mental health assessment, physical fitness evaluation, timing and content of health education, development of personalized exercise prescriptions, and risk control. Conclusion: In clinical settings, using evidence-based practices requires developing feasible intervention programs based on comprehensive consideration of hospital resources, allocation of medical personnel, and consideration of patients' preferences to reduce the kinesophobia of patients post-PCI and improve their compliance with exercise rehabilitation.

8.
Plant Physiol ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39321167

ABSTRACT

Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum (Lib.) De Bary is a devastating disease infecting hundreds of plant species. It also restricts the yield, quality, and safe production of rapeseed (Brassica napus) worldwide. However, the lack of resistance sources and genes to S. sclerotiorum has greatly restricted rapeseed SSR-resistance breeding. In this study, a previously identified GDSL motif-containing lipase gene, Brassica napus GDSL LIPASE-LIKE 1 (BnaC07.GLIP1), encoding a protein localized to the intercellular space, was characterized as functioning in plant immunity to S. sclerotiorum. The BnaC07.GLIP1 promoter is S. sclerotiorum-inducible and the expression of BnaC07.GLIP1 is substantially enhanced after S. sclerotiorum infection. Arabidopsis (Arabidopsis thaliana) heterologously expressing and rapeseed lines overexpressing BnaC07.GLIP1 showed enhanced resistance to S. sclerotiorum, whereas RNAi suppression and CRISPR/Cas9 knockout B. napus lines were hyper-susceptible to S. sclerotiorum. Moreover, BnaC07.GLIP1 affected the lipid composition and induced the production of phospholipid molecules, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidic acid, which were correlated with decreased levels of reactive oxygen species (ROS) and enhanced expression of defense-related genes. A B. napus bZIP44 transcription factor specifically binds the CGTCA motif of the BnaC07.GLIP1 promoter to positively regulate its expression. BnbZIP44 responded to S. sclerotiorum infection, and its heterologous expression inhibited ROS accumulation, thereby enhancing S. sclerotiorum resistance in Arabidopsis. Thus, BnaC07.GLIP1 functions downstream of BnbZIP44 and is involved in S. sclerotiorum resistance by modulating the production of phospholipid molecules and ROS homeostasis in B. napus, providing insights into the potential roles and functional mechanisms of BnaC07.GLIP1 in plant immunity and for improving rapeseed SSR disease-resistance breeding.

9.
Metabolites ; 14(9)2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39330499

ABSTRACT

To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis.

10.
bioRxiv ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39282437

ABSTRACT

Multi-omic data-driven studies, characterizing complex disease signaling system from multiple levels, are at the forefront of precision medicine and healthcare. The integration and interpretation of multi-omic data are essential for identifying molecular targets and deciphering core signaling pathways of complex diseases. However, it remains an open problem due the large number of biomarkers and complex interactions among them. In this study, we propose a novel Multi-scale Multi-hop Multi-omic graph model, M3NetFlow, to facilitate generic multi-omic data analysis to rank targets and infer core signaling flows/pathways. To evaluate M3NetFlow, we applied it in two independent multi-omic case studies: 1) uncovering mechanisms of synergistic drug combination response (defined as anchor-target guided learning), and 2) identifying biomarkers and pathways of Alzheimer 's disease (AD). The evaluation and comparison results showed M3NetFlow achieves the best prediction accuracy (accurate), and identifies a set of essential targets and core signaling pathways (interpretable). The model can be directly applied to other multi-omic data-driven studies. The code is publicly accessible at: https://github.com/FuhaiLiAiLab/M3NetFlow.

11.
JAMA Netw Open ; 7(9): e2436136, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39331397

ABSTRACT

This cohort study examined the differences in prehospital treatment received by patients with traumatic injury belonging to different racial and ethnic groups between 2013 and 2020 in Los Angeles County.


Subject(s)
Black or African American , Emergency Medical Services , Wounds and Injuries , Humans , Los Angeles , Male , Wounds and Injuries/therapy , Wounds and Injuries/ethnology , Female , Adult , Black or African American/statistics & numerical data , Middle Aged
12.
Anal Chem ; 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39340422

ABSTRACT

Coagulation factor XIa (FXIa) is associated with a low risk of bleeding and has been identified as an effective and safe target for the development of novel anticoagulant drugs. In this study, we established an ultrasensitive competitive dual-enzyme cascade signal amplification method for the quantitative analysis and screening of FXIa inhibitors. Due to the specific recognition of FXIa's active site by the aptamer AptE40, the AptE40-QDs-EK recognition probe modified with enterokinase (EK) and the aptamer AptE40, was attached to the MNPs-FXIa capture probe. When FXIa inhibitor was present, it competed with AptE40 for binding to FXIa, resulting in the detachment of AptE40-QDs-EK from MNPs-FXIa. After magnetic separation, the enterokinase of AptE40-QDs-EK in the supernatant hydrolyzed N-terminal hexapeptide of trypsinogen, leading to the production of a large amount of trypsin as part of the first-stage signal cascade amplification. Next, trypsin could hydrolyze the hexameric arginine peptide (RRRRRR, R6), leading to the dissociation of RQDs from the R6-RQDs signal probe; this resulted in a dramatic increase in the fluorescence intensity of the supernatant as the second-stage signal cascade was amplified. The feasibility of the method was investigated using the FXIa inhibitor aptamer FELIAP as a positive model drug. Furthermore, the method was applied to screen the FXIa inhibitors in Eupolyphaga sinensis Walker. Two fractions with more active anticoagulated ingredients were successfully identified and validated via the conventional method, and the results were consistent. The established method provides a key technique for the sensitive detection, high-throughput analysis, and screening of the FXIa inhibitors.

13.
J Am Soc Mass Spectrom ; 35(10): 2499-2506, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39258819

ABSTRACT

It is extremely difficult to inject a low-energy electron beam into a conventional radiofrequency (RF) linear ion trap for electron capture dissociation (ECD) without using a magnetic field to focus the electrons. In this study, the dynamic process of electrons in an RF field during their injection and transmission through a linear ion trap was simulated to determine the range of the RF phase where the electrons can be decelerated to meet the energy requirement for ECD. The ECD time window was expanded by applying a time-dependent compensation voltage to the cathode. The relationship between the cathode voltage and the phase of the RF voltage was determined. The ECD time window was increased to 49.4% of the total RF cycle after applying a compensation voltage. Between the phases of RF voltage of 0 and 0.975 π, at least 98.7% of electrons can be injected into the ECD reaction zone, and 94% of them had an energy less than 3 eV. The range of electron energy can also easily be shifted upward to enable hot electron capture dissociation.

14.
Front Immunol ; 15: 1454823, 2024.
Article in English | MEDLINE | ID: mdl-39247188

ABSTRACT

Protein post-translational modifications (PTMs) represent a crucial aspect of cellular regulation, occurring after protein synthesis from mRNA. These modifications, which include phosphorylation, ubiquitination, acetylation, methylation, glycosylation, Sumoylation, and palmitoylation, play pivotal roles in modulating protein function. PTMs influence protein localization, stability, and interactions, thereby orchestrating a variety of cellular processes in response to internal and external stimuli. Dysregulation of PTMs is linked to a spectrum of diseases, such as cancer, inflammatory diseases, and neurodegenerative disorders. UFMylation, a type of PTMs, has recently gained prominence for its regulatory role in numerous cellular processes, including protein stability, response to cellular stress, and key signaling pathways influencing cellular functions. This review highlights the crucial function of UFMylation in the development and progression of tumors, underscoring its potential as a therapeutic target. Moreover, we discuss the pivotal role of UFMylation in tumorigenesis and malignant progression, and explore its impact on cancer immunotherapy. The article aims to provide a comprehensive overview of biological functions of UFMylation and propose how targeting UFMylation could enhance the effectiveness of cancer immunotherapy strategies.


Subject(s)
Carcinogenesis , Immunotherapy , Neoplasms , Protein Processing, Post-Translational , Humans , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/metabolism , Immunotherapy/methods , Carcinogenesis/immunology , Animals , Signal Transduction
15.
Adv Sci (Weinh) ; : e2403389, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264289

ABSTRACT

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress-related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome-related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte-specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive-like behaviors by inhibiting lysosomal exocytosis-mediated adenosine 5'-triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive-like behaviors induced by astrocyte-specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress-sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.

16.
Animals (Basel) ; 14(17)2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39272296

ABSTRACT

Dietary lipids provide energy for animals and can also be converted into other nutrients (such as non-essential amino acids), which play a role in saving protein. The Chinese stripe-necked turtle is a protected and endangered species that has been bred in captivity; however, basic data on lipid requirements remain unavailable. In this study, 360 Mauremys sinensis (body weight of 65.32 ± 0.15 g) were randomly divided into six groups with three replicates per group; the turtles were fed experimental diets supplemented with various levels of fish oil (i.e., 1% (control group, CG), 3.5% (HF-1), 6% (HF-2), 8.5% (HF-3), 11% (HF-4), and 13.5% (HF-5)) for 10 weeks. The results showed that compared with CG, increasing the fish oil level promoted the growth performance of turtles, and the HF-3 group achieved the best effect. The HF-4 group showed the highest increases in the hepatosomatic index and viscerosomatic index. In addition, increased lipid levels also increased the crude lipid content and reduced the crude protein content in muscle tissue. Oil red O staining showed that the liver lipid content increased with the level of supplemented fish oil, which is consistent with the results of the hepatosomatic index. Compared with CG, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased significantly in both the liver and serum when fish oil levels exceeded 8.5% (p < 0.05), while high-density lipoprotein cholesterol decreased significantly. Aspartate transaminase and cerealthirdtransaminase levels in serum increased significantly when fish oil levels exceeded 8.5% (p < 0.05). Moreover, the activities of antioxidant enzymes (GSH-Px, SOD, T-AOC, and CAT) and MDA showed similar results, indicating that high fish oil levels (8.5-13.5%) caused liver tissue damage in M. sinensis. Increased fish oil levels significantly upregulated the expression levels of cytokines (IFN-γ, TNF-α, TGF-ß1, IL-10, and IL-12) (p < 0.05), downregulated the expression levels of antioxidant enzyme-related genes (cat, mn-sod, and gsh-px), and increased apoptosis of liver cells. Supplementation of the diet with 3.5-6% fish oil improved the growth performance of M. sinensis, and the turtles maintained a beneficial immune status. The results provide a scientific basis for optimizing the commercial feed formula of M. sinensis.

17.
Heliyon ; 10(17): e37057, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39286135

ABSTRACT

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125136, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39299075

ABSTRACT

Thrombin plays a critical role in hemostasis and hemolysis, and is a significant biomarker for blood-related diseases. Detection and inhibitors screening of thrombin are essential in medical research. In this study, we developed a fluorescent sensor based on the interaction between quantum dots (QDs) and fibrinogen (Fib) for thrombin detection and its inhibitors screening. Upon the presence of thrombin, the fibrinogen of soluble QDs-Fib were converted into insoluble fibrin precipitate, causing a change of fluorescence intensity in the supernatant. Under optimized conditions, our method exhibited an excellent linearity (R2 ≥0.99) over the range of 2∼100 U/L with a limit of detection (LOD) as low as 0.29 U/L. Moreover, we employed this method to screen for thrombin inhibitors using dabigatran as an exemplary direct thrombin inhibitor (DTI), even at concentrations as low as 1 nM. Finally, the established method was successfully used to screen thrombin inhibitors in 23 different extracts from Eupolyphaga sinensis walker. The method provided not only a sensitive, specific and high throughput assay for the detection of thrombin activity in biological samples, but also a reliable strategy for the screening of thrombin inhibitors in complex matrices.

19.
Adv Mater ; : e2409618, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225412

ABSTRACT

Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form of inflammatory programmed cell death, presents a dependable strategy for combating cancer by engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis). In this study, an ultrasmall Bi2Sn2O7 nanozyme with ultrasound-magnified multienzyme-mimicking properties is designed and engineered as a PANoptosis inducer through destroying the mitochondrial function of tumor cells and enhancing the intracellular accumulation of toxic reactive oxygen species, finally triggering the activation of PANoptosis process. The role of PANoptosis inducer has been verified by the expression of related proteins, including cleaved Caspase 3, NLRP3, N-GSDMD, cleaved Caspase 1, p-MLKL, and RIPK3. The inclusion of external ultrasonic irradiation significantly augments the enzyodynamic therapeutic efficiency. In vitro and in vivo antineoplastic efficacy, along with inhibition of lung metastasis, validate the benefits of the Bi2Sn2O7-mediated PANoptosis pathway. This study not only elucidates the intricate mechanisms underlying Bi2Sn2O7 as a PANoptosis inducer, but also offers a novel perspective for the treatment of hepatocellular carcinoma.

20.
Food Chem ; 463(Pt 1): 141050, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39236384

ABSTRACT

In this study, rice husk biochar was engineered with abundant iron ion sites to enhance the enrichment of antioxidant peptides from rice protein hydrolysates through metal-chelating interactions. The π-π interactions and metal ion chelation were identified as the primary mechanisms for the enrichment process. Through peptide sequencing, four peptides were identified: LKFL (P1: Leu-Lys-Phe-Leu), QLLF (P2: Gln-Leu-Leu-Phe), WLAYG (P3: Trp-Leu-Ala-Tyr-Gly), and HFCGG (P4: His-Phe-Cys-Gly-Gly). The vitro analysis and molecular docking revealed that peptides P1-P4 possessed remarkable scavenging ability against radicals and Fe2+ chelating ability. Notably, peptide P4 showed radical scavenging activity comparable to glutathione (GSH) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals. Cellular experiments further confirmed that peptide P4 effectively protected HepG2 cells from oxidative stress-induced damage. The modified rice husk biochar proved to be an effective means for enriching rice antioxidant peptides from protein hydrolysates.

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