Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity.

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 expression was reduced in patients with IBD. Npm1+/- mice were more susceptible to acute colitis and experimentally induced CAC than littermate controls. Npm1 deficiency impaired the function of interleukin-22 (IL-22)-producing group three innate lymphoid cells (ILC3s). Mice lacking Npm1 in ILC3s exhibited decreased IL-22 production and accelerated development of colitis. NPM1 was important for mitochondrial biogenesis and metabolism by oxidative phosphorylation in ILC3s. Further experiments revealed that NPM1 cooperates with p65 to promote mitochondrial transcription factor A (TFAM) transcription in ILC3s. Overexpression of Npm1 in mice enhanced ILC3 function and reduced the severity of dextran sulfate sodium-induced colitis. Thus, our findings indicate that NPM1 in ILC3s protects against IBD by regulating mitochondrial metabolism through a p65-TFAM axis.

Cudraflavone B induces human glioblastoma cells apoptosis via ER stress-induced autophagy.

BACKGROUND: Glioblastoma (GBM) is the most common malignant intracranial tumor with a low survival rate. However, only few drugs responsible for GBM therpies, hence new drug development for it is highly required. The natural product Cudraflavone B (CUB) has been reported to potentially kill a variety of tumor cells. Currently, its anit-cancer effect on GBM still remains unknown. Herein, we investigated whether CUB could affect the proliferation and apoptosis of GBM cells to show anti-GBM potential. RESULTS: CUB selectively inhibited cell viability and induced cell apoptosis by activating the endoplasmic reticulum stress (ER stress) related pathway, as well as harnessing the autophagy-related PI3K/mTOR/LC3B signaling pathway. Typical morphological changes of autophagy were also observed in CUB treated cells by microscope and scanning electron microscope (SEM) examination. 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, restored the CUB-caused alteration in signaling pathway and morphological change. CONCLUSIONS: Our finding suggests that CUB impaired cell growth and induced cell apoptosis of glioblastoma through ER stress and autophagy-related signaling pathways, and it might be an attractive drug for treatment of GBM.

Occurrence of bisphenol diglycidyl ethers and bisphenol analogs, and their associations with DNA oxidative damage in pregnant women.

Bisphenol diglycidyl ethers (BDGEs) and Bisphenol A and its analogs (bisphenols) may have the same exposure routes and coexposure phenomenon in sensitive populations such as pregnant women. Previous biomonitoring studies on BDGEs are limited. Levels of fifteen bisphenols, six BDGEs and the DNA oxidative damage biomarker 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured in the urine of pregnant women recruited in south China (n = 358). We aimed to provide the occurrence of bisphenols and BDGEs in pregnant women, and to investigate the potential relationship between their exposure and oxidative stress. Bisphenol A, bisphenol S, bisphenol F, bisphenol AP and all BDGEs (except for BADGE·2HCl) were frequently detected. The total concentrations of all bisphenols and BDGEs were 0.402-338 and 0.104-32.5 ng/mL, with geometric means of 2.87 and 2.48 ng/mL, respectively. BFDGE was the most abundant chemical of BDGEs, with a median concentration of 0.872 ng/mL, followed by BADGE·H2O·HCl (0.297 ng/mL). Except for pre-pregnancy obesity, maternal age/height, employment, fasting in the morning and parity did not affect the urinary concentrations of BDGEs. Significant and weak correlations were observed between concentrations (unadjusted) of total bisphenols and BDGEs (r = 0.389, p < 0.01), indicating their similar sources and exposure routes. The biomarker 8-OHdG was detected in all samples, with concentrations ranging from 1.98 to 32.6 ng/mL (median: 9.96 ng/mL). Levels of 8-OHdG were positively correlated with urinary several bisphenol concentrations (adjusted ß range: 0.037-0.089, p < 0.05) but were not correlated with those of BDGEs. Further studies should focus on whether BDGEs and bisphenols exert combined effects on oxidative stress. Our study provided the first BDGEs exposure data in pregnant women and indicated that BDGEs exposure was highly prevalent in pregnant women as early as 2015 in south China.

Three thermal treated methods improve physicochemical and functional properties of wheat bran-germ and the bran-germ containing products.

BACKGROUND: To fully investigate the effect of different stabilization methods on WBG in the same environment, we studied the effect of microwaving, baking, and extrusion on the nutritional, physicochemical, and processability properties of WBG and whole wheat bran-germ noodle (WBGN). Principal component analysis was used to comprehensively evaluate the qualities of WBG and WBGN. Machine learning-based research was conducted to predict the quality of WBGN based on the features of WBG. RESULTS: The results showed that three methods improved antioxidant ability, bound flavonoids, bound and total phenolics, and the processing properties in WBG (P < 0.05). Extruded-WBG showed a lower polyphenol oxidase activity, lipase activity (35.02 ± 2.02 U and 20.29 ± 0.47 mg g-1 ) and particle size (54.08 ± 0.38 µm), and higher water hold capacity (2.60 ± 0.68%) and bound phenolic levels. The enhanced quantity of bound polyphenols had a major role in the increased antioxidant potential of WBGN. Extruded-WBGN showed higher antioxidant ability for 2,2-diphenyl-1-picrylhydrazyl (171.28 ± 3.16 µmol Trolox eq kg-1 ). The extruded-WBGN had high concentrations of WBG aroma compounds, and low contents of bitterness and raw bran-germ flavor compounds. Next, the enzymatic activity, powder properties, color, and antioxidant capacity of WBG were further utilized to predict the polyphenolic, flavonoids, flavor compounds, and antioxidant capacities of WBGN, where the R2 value of the model exceeded 0.90. The best comprehensive quality modification method of the WBG and WBGN was extrusion, followed by baking and microwaving. CONCLUSION: The present study shows that extrusion is a promising way to improve WBG into a nutritious and flavorful cereal food ingredient. © 2023 Society of Chemical Industry.

Core microbes closely related with the nutrients and flavor of sweet fermented oats (whole grain food) from China.

Increased attention has been given to whole grain and plant-based foods due to health concerns. Sweet fermented oats (SFOs) are such traditional fermented food from China. However, reports on their microbiota and relations with the nutrients and flavor were scarcely few, hindering their wider application. The comprehensive microbial composition, metabolic compounds and their correlations of representative SFOs from northwestern China were firstly investigated. Firmicutes predominated the microbial communities, followed by Proteobacteria. Weissella, Bacillus and Lactobacillus were dominant bacterial genera, biomarkers and core bacteria as well. GC-MS (Gas Chromatography-Mass Spectrometer) identified the metabolic compounds, among which the categories fatty acids and carboxylic acids most abundant. Eighteen chemicals showed significant differences among the five SFOs, including ethyl octanoate, neryl acetate, L-sorbose, diglycerol, cellotetraose etc. Fatty acids, carboxylic acids, amino acids, peptides, oligosaccharides, and monosaccharides were the key substances responsible for the unique flavor and rich nutrients in SFOs. The core bacteria were closely related to chemical acids, esters, flavone and alcohol. Pediococcus showed a negative correlation with 2,3-butanediol. SFOs were made in the laboratory with the core bacterial strains, obtaining a high abundance of nutrient chemicals and sensory evaluation value. The research provided a foundation for the improvement, further application and industrialization of SFOs.

The impact of prophylactic ascending aorta replacement on the long-term prognosis of zone 0 hybrid arch repair.

OBJECTIVES: To investigate the impact of prophylactic zone 0 replacement with prosthetic grafts on the long-term prognosis and perioperative safety of zone 0 hybrid arch repair (HAR) when zone 0 is neither dilated nor pathologic. METHODS: We retrospectively reviewed 115 patients whose zone 0 aorta was neither dilated nor pathologic and who underwent zone 0 HAR from January 2009 to December 2020 and divided then into two groups depending on whether zone 0 was replaced, with 46 patients in the no-replacement group and 69 patients in the replacement group. Inverse probability of treatment weighting (IPTW) was used to balance the baseline difference, and outcomes were compared after IPTW adjustment. The primary end points were overall survival and adverse aortic events (AAEs). The secondary end points were early composite adverse events and other perioperative complications. Subgroup analysis was performed by age, diagnosis, zone 0 maximum diameter and risk stratification. RESULTS: The 5-year IPTW-adjusted overall survival rate was 84% in the no-replacement group 90% in the replacement group (P = .61). With death as a competing risk, the IPTW-adjusted cumulative incidence of AAEs at 5 and 10 years was 23% and 41% in the no-replacement group, and 14% and 25% in the replacement group, respectively (subdistribution hazard ratio [sHR], 0.56; 95% confidence interval [CI], 0.23-1.39; P = .23). Considering proximal complications alone, the replacement group exhibited lower 5-year (3% vs 18%) and 10-year (6% vs 36%) cumulative incidences of proximal complications (sHR, 0.11; 95% CI, 0.01-0.91; P = .04) after IPTW adjustment. A subgroup analysis demonstrated that the benefits of zone 0 replacement in decreasing AAEs were observed in those aged 60 years or less (sHR, 0.15; 95% CI, 0.03-0.75; P = .02) and those with type B aortic dissection (sHR, 0.24; 95% CI, 0.07-0.82; P = .02). Additionally, zone 0 replacement did not increase early composite adverse event morbidity (9% vs 21%; P = .08) or early mortality (7% vs 6%; P = .87). CONCLUSIONS: Although zone 0 was neither dilated nor pathologic, prophylactic zone 0 replacement in zone 0 HAR significantly decreased the incidence of proximal complications, without impairing perioperative safety. Additionally, this strategy was associated with benefits in reducing AAEs in younger patients and patients with type B aortic dissection. Thus, prophylactic zone 0 replacement should be considered for reconstructing a stable proximal landing zone in zone 0 HAR.

Bibliometric analysis of the inflammatory mechanism in aortic disease.

BACKGROUND: In view of the key role of inflammation in the pathogenesis of aortic disease, we visually analyzed the research hotspots of inflammatory mechanism in aortic disease in this work through the method of bibliometrics from the Web of Science (WOS) Core database over the past three decades. METHODS: A visual bibliometric network of research articles on inflammatory mechanisms in aortic disease was obtained from VOSviewer and Citespace based on the WOS Core Collection. RESULTS: A total of 1278 documents from January 1990 to February 2021 were selected for analysis. The United States and China had the highest percentage of articles, comprising 34.01% and 24.92% of articles worldwide, respectively. Harvard University has published the most articles in this field, followed by the University of Michigan and Huazhong University of Science and Technology. The top 3 research hotspots were atherosclerosis, oxidative stress, and macrophages. The journal with the most articles in this area was Arteriosclerosis Thrombosis and Vascular Biology, followed by Atherosclerosis and PLOS One. The research trend on inflammatory mechanisms in the aortic system has 5 distinct directions: (1) atherosclerosis, NF-κB, expression, smooth muscle cell, and oxidative stress; (2) coronary artery disease, C-reactive protein, risk factors, endothelial dysfunction, and aortic stenosis; (3) abdominal aortic aneurysm, matrix metalloproteinases, macrophage, and pathogenesis; (4) cholesterol, metabolism, low-density lipoprotein, gene expression, and a therosclerotic lesions; and (5) calcific aortic valve disease, interstitial cells, calcification, and stenosis. CONCLUSIONS: Inflammatory mechanism research has shown a tendency to rise gradually in the aortic field. Numerous studies have explored the role of inflammatory responses in aortic disease, which may increase the risk of endothelial dysfunction (aortic fibrosis and stiffness) and induce plaque formation. Among them, NFκB activation, nitric-oxide synthase expression, and oxidative stress are particularly essential.

The Relationship between the Incidence of Postoperative Cognitive Dysfunction and Intraoperative Regional Cerebral Oxygen Saturation after Cardiovascular Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: To assess whether intraoperative monitoring and intervention of regional cerebral oxygen saturation levels can reduce the incidence of postoperative cognitive dysfunction in patients undergoing cardiovascular surgery and contribute to patient prognosis. Methods: The Cochrane Library, PubMed, and the Web of Science were systematically searched for relevant randomized controlled trials involving the effects of cerebral oxygen saturation on the cognitive function of patients after cardiovascular surgery from January 1, 2000 to May 1, 2022. The primary outcome was the incidence of postoperative cognitive dysfunction. The secondary outcomes were length of hospital stay, length of intensive care unit (ICU) stay, length of mechanical ventilation, length of cardiopulmonary bypass, and other major postoperative outcomes such as renal failure, infection, arrhythmia, hospital mortality, and stroke. Data were pooled using the risk ratio or standardized mean difference with 95% confidence interval (CI). The original study protocol was registered prospectively with PROSPERO (CRD42020178068). Results: A total of 13 randomized controlled trials involving 1669 cardiovascular surgery patients were included. Compared with the control group, the risk of postoperative cognitive dysfunction was significantly lower in the intervention group (RR = 0.50; 95% CI: 0.30 to 0.85; p = 0.01; I 2 = 71%). The Duration of stay in intensive care units in the intervention group was also significantly shorter than that in the control group (standard mean difference (SMD) = -0.14; 95% CI: -0.26 to -0.01; p = 0.03; I 2 = 26%). Univariate meta-regression analyses showed that age is a major source of heterogeneity. Conclusions: Our current study suggests that intraoperative cerebral oxygen saturation monitoring and intervention can significantly reduce the incidence of postoperative cognitive dysfunction, and the length of intensive care unit stay after intervention is considerably reduced. Given that some limits in this review, more high-quality, and long-term trials are still needed to certify our findings.

Biohybrid Organic Heterostructure Based on Chlorophyll-Bacteriochlorophyll Aggregates for Ecofriendly Hydrogen Production.

Hydrogen energy is an abundant, clean, sustainable and environmentally friendly renewable energy source. Therefore, the production of hydrogen by photocatalytically splitting water on semiconductors has been considered in recent years as a promising and sustainable strategy for converting solar energy into chemical energy to replace conventional energy sources and to solve the growing problem of environmental pollution and the global energy crisis. However, highly efficient solar-driven photocatalytic hydrogen production remains a huge challenge due to the poor visible light response of available photocatalytic materials and the low efficiency of separation and transfer of photogenerated electron-hole pairs. In the present work, organic heterojunction structures based on bacteriochlorophyll (BChl) and chlorophyll (Chl) molecules were introduced and used for solar-driven photocatalytic hydrogen production from water under visible light. Also, noble metal-free photocatalyst was successfully constructed on Ti3 C2 Tx nanosheets by simple successive deposition of Chl and BChl, which was used for the photocatalytic splitting water to hydrogen evolution reaction (HER). The results show that the optimal BChl@Chl@Ti3 C2 Tx composite has a high HER performance with 114 µmol/h/gcat , which is much higher than the BChl@Ti3 C2 Tx and Chl@Ti3 C2 Tx composites.

Reconsideration and surgical technique report of root repair management of acute Stanford type A aortic dissection.

Currently, there is a lack of expert consensus and clinical guidelines about the treatment strategy for aortic roots in patients with acute Stanford type A aortic dissection with aortic sinuses less than 45 mm in diameter and without combined connective tissue disorder. The physiological aortic sinus plays a key role in the protection of the aortic valve and cardiac function. Thus, we invented a "watching without dealing with" technique of aortic root repair to preserve the aortic sinus as much as possible. This technique could simplify the operation and improve the patient's prognosis, which is worth learning and promoting.

Thermal Conductivity Gas Sensor with Enhanced Flow-Rate Independence.

In this article, novel thermal gas sensors with newly designed diffusion gas channels are proposed to reduce the flow-rate disturbance. Simulation studies suggest that by lowering the gas flow velocity near the hot film, the maximum normalized temperature changes caused by flow-rate variations in the two new designs (Type-H and Type-U) are decreased to only 1.22% and 0.02%, which is much smaller than in the traditional straight design (Type-I) of 20.16%. Experiment results are in agreement with the simulations that the maximum normalized flow-rate interferences in Type-H and Type-U are only 1.51% and 1.65%, compared to 24.91% in Type-I. As the introduced CO2 flow varied from 1 to 20 sccm, the normalized output deviations in Type-H and Type-U are 0.38% and 0.02%, respectively, which are 2 and 3 orders of magnitude lower than in Type-I of 10.20%. In addition, the recovery time is almost the same in all these sensors. These results indicate that the principle of decreasing the flow velocity near the hot film caused by the two novel diffusion designs can enhance the flow-rate independence and improve the accuracy of the thermal conductivity as well as the gas detection.

Hsa_circ_0000520 overexpression increases CDK2 expression via miR-1296 to facilitate cervical cancer cell proliferation.

BACKGROUND: Circular RNA (circRNA) has been demonstrated to participate in cervical cancer development. In this study, we analyzed the role of hsa_circ_0000520 in cervical cancer. METHODS: Fifty-two pairs of cervical cancer and adjacent normal tissue samples were collected, and five human cervical cancer cell lines were obtained followed by the detection of hsa_circ_0000520 expression. Nuclear-cytoplasmic isolation and fluorescence in situ hybridization were performed to analyze the subcellular localization of hsa_circ_0000520 while linear RNA was digested by RNase R. Gain- or loss-of function experiments on hsa_circ_0000520 were performed, followed by detection of cell proliferation and cell cycle by EdU, Cell Counting Kit-8, colony formation assay, and flow cytometry respectively. RESULTS: Hsa_circ_0000520 and cyclin-dependent kinase 2 (CDK2) were highly expressed in cervical cancer tissues. Binding sites between microRNA-1296 (miR-1296) and hsa_circ_0000520 or CDK2 were verified. Antibody to Argonaute 2 (Ago2) could precipitate hsa_circ_0000520, indicating that hsa_circ_0000520 could competitively bind to miR-1296 via Ago2. Silencing hsa_circ_0000520 inhibited cervical cancer cell proliferation and promoted the inhibitory effects of miR-1296 on CDK2, thereby blocking cell cycle progression and promoting apoptosis. CONCLUSION: These results support the premise that targeting hsa_circ_0000520 can be a potential approach to combat cervical cancer.

Overexpression of microRNA-367 inhibits angiogenesis in ovarian cancer by downregulating the expression of LPA1.

BACKGROUND: Compelling evidences reported the role of microRNAs (miRNAs) in ovarian cancer. However, little was known regarding the molecular mechanism of miR-367 in ovarian cancer. This study intended to investigate the role and regulatory mechanism of miR-367 in ovarian cancer involving lysophosphatidic acid receptor-1 (LPA1). METHODS: Potentially regulatory miRNAs in ovarian cancer were obtained from bioinformatics analysis. RT-qPCR was used to detect miR-367 expression in both ovarian cancer tissues and relevant adjacent normal tissues. Relationship between miR-367 and LPA1 was predicted by miRNA database and further verified using dual luciferase reporter gene assay and RIP. EdU and Transwell assay were used to measure the proliferation and invasion ability of cells. Moreover, tube formation and chick chorioallantois membrane (CAM) assay were performed to determine angiogenesis of human umbilical vein endothelial cells (HUVECs). Finally, the roles of LPA1 in tumor growth was also studied using nude mice xenograft assay. RESULTS: High expression of LPA1 and low expression of miR-367 were observed in ovarian cancer tissues and cells. Overexpressed miR-367 downregulated LPA1 expression to inhibit proliferation, invasion, and angiogenesis of cancer cells. Low expression of LPA1 suppressed tumor formation and repressed angiogenesis in ovarian in vivo. CONCLUSION: All in all, overexpression of miR-367 downregulated LPA1 expression to inhibit ovarian cancer progression, which provided a target for the cancer treatment.

Preparation and evaluation of rotigotine-loaded implant for the treatment of Parkinson's disease and its evolution study.

PURPOSE: To develop rotigotine-loaded implants (RI) to achieve continuous release of rotigotine for long duration for the treatment of Parkinson's disease (PD). METHODS: RI was prepared by hot-melt extrusion method using poly (lactide-co-glycolide) (PLGA) as the matrix. In vitro drug release was optimized by drug loading, melting temperature during preparing process and additives. The surface and internal morphology of RI was imaged by SEM. The in vivo release profile of RI was investigated on rat. RESULTS: RI prepared with PLGA 7525 5A showed sustained release of 40 days while suffering a lag phase, which was significantly shortened by blending 5050 2A and mannitol in the matrix. RI prepared by 7525 5A/5050 2A/mannitol = 55:10:5 (rotigotine 30%) showed a 40-day sustained release in vivo with no lag phase. The drug release from RI was also affected by drug loading and melting temperature probably due to the drug state existed in the implant. The evolution of implants during release process was correlated well with the drug release kinetics. CONCLUSION: RI could achieve sustained drug release for 40 days which could supply an alternative of continuous dopaminergic stimulation (CDS) for the treatment of PD.

Ultra-compact dual-channel integrated CO2 infrared gas sensor.

Expiratory CO2 concentrations can directly reflect human physiological conditions, and their detection is highly important in the treatment and rehabilitation of critically ill patients. Existing respiratory gas analyzers suffer from large sizes and high power consumption due to the limitations of the internal CO2 sensors, which prevent them from being wearable to track active people. The internal and external interference and sensitivity limitations must be overcome to realize wearable respiratory monitoring applications for CO2 sensors. In this work, an ultra-compact CO2 sensor was developed by integrating a microelectromechanical system emitter and thermopile detectors with an optical gas chamber; the power consumption of the light source and ambient temperature of the thermally sensitive devices were reduced by heat transfer control; the time to reach stabilization of the sensor was shortened; the humidity resistance of the sensor was improved by a dual-channel design; the light loss of the sensor was compensated by improving the optical coupling efficiency, which was combined with the amplitude trimming network to equivalently improve the sensitivity of the sensor. The minimum size of the developed sensor was 12 mm × 6 mm × 4 mm, and the reading error was <4% of the reading from -20 °C to 50 °C. The minimum power consumption of the sensor was ~33 mW, and the response time and recovery time were 10 s (@1 Hz), and the sensor had good humidity resistance, stability, and repeatability. These results indicate that the CO2 sensor developed using this strategy has great potential for wearable respiratory monitoring applications.

Aortic diameter remodeling after frozen elephant trunk as a predictor of early outcomes in thoracoabdominal aortic repair.

OBJECTIVE: Patients who underwent previous frozen elephant trunk implantation for Stanford type A aortic dissection remain at risk for secondary intervention due to unsuccessful distal aortic remodeling. We aimed to investigate the impact of distal aortic remodeling on early outcomes in patients who underwent 2-stage thoracoabdominal aortic repair. METHODS: A total of 106 patients who previously underwent frozen elephant trunk implantation and thoracoabdominal aortic repair between October 2014 and December 2022 were enrolled in this study. The extent of distal aortic remodeling was evaluated, including aortic diameter, area ratio of the false lumen/aortic lumen, and patency of the false lumen at 3 levels of the aorta. Logistic regression analyses were performed to investigate the risk factors for early outcomes. RESULTS: The aortic diameter at the distal frozen elephant trunk was significantly larger in patients who died early than in surviving patients (79.19 ± 22.89 mm vs 46.84 ± 19.17 mm, respectively, adjusted P = .001). The optimal cutoff value for the aortic diameter at the distal frozen elephant trunk was 60 mm. Patients with an aortic diameter 60 mm or more at the distal frozen elephant trunk had worse early outcomes (P < .05), including prolonged intubation, early death, and postoperative complications. The aortic diameter at the distal frozen elephant trunk was identified as a significant risk factor for early death in patients undergoing thoracoabdominal aortic repair. CONCLUSIONS: Patients undergoing thoracoabdominal aortic repair with an aortic diameter 60 mm or more at the distal frozen elephant trunk have worse early outcomes. Moreover, an aortic diameter at the distal frozen elephant trunk is a significant risk factor for early death in patients undergoing thoracoabdominal aortic repair.

Delivery of SIRT1 by cancer-associated adipocyte-derived extracellular vesicles regulates immune response and tumorigenesis of ovarian cancer cells.

PURPOSE: This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). METHODS: Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. RESULTS: CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. CONCLUSION: CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells.

Novel meroterpene-like compounds inhibit ferroptosis through Fe2+ chelation.

Colorectal cancer (CRC) is the third most common type of cancer in the world. It is characterized by complex crosstalk between various signaling pathways, as a result of which it is highly challenging to identify optimal therapeutic targets and design treatment strategies. In this study, we tested the effect of 700 compounds on the CRC cell line HT-29 by using the sulforhodamine B assay and screened out 17 compounds that exhibited high toxicity (indicated by an inhibition rate of ≥75 % when applied at a concentration of 10 µM) against the HT-29 cell line. Next, we investigated the mechanisms underlying the effects of these 17 highly toxic compounds. The results of ferroptosis analysis and electron microscopy showed that compounds 575 and 578 were able to significantly reverse RSL3-induced increase in ferroptosis, while compound 580 had a less pronounced ferroptosis-regulating effect. In subsequent experiments, western blotting showed that compounds 575, 578, and 580, which belong to a class of meroterpene-like compounds that affect ferroptosis, do not induce autophagy or apoptosis in the CRC cell line. Instead, Fe2+ chelation experiments showed that these three compounds can serve as iron chelators by chelating Fe2+ at a 1:1 (chelator: Fe2+) ratio. Specifically, the aldehyde and hydroxyl groups of the benzene ring in these compounds may chelate Fe2+, thus reducing Fe2+ levels in cells and inhibiting ferroptosis. These results indicate that these novel meroterpene-like compounds are potential therapeutic small-molecule candidates for targeting ferroptosis in tumors.

A novel prognostic signature based on cancer stemness and metabolism-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma.

BACKGROUND: CESC is the second most commonly diagnosed gynecological malignancy. Given the pivotal involvement of metabolism-related genes (MRGs) in the etiology of multiple tumors, our investigation aims to devise a prognostic risk signature rooted in cancer stemness and metabolism. METHODS: The stemness index based on mRNA expression (mRNAsi) of samples from the TCGA dataset was computed using the One-class logistic regression (OCLR) algorithm. Furthermore, potential metabolism-related genes related to mRNAsi were identified through weighted gene co-expression network analysis (WGCNA). We construct a stemness-related metabolic gene signature through shrinkage estimation and univariate analysis, thereby calculating the corresponding risk scores. Moreover, we selected corresponding DEGs between groups with high- and low-risk score and conducted routine bioinformatic analyses. Furthermore, we validated the expression of four hub genes at the protein level through immunohistochemistry (IHC) in samples obtained from our patient cohort. RESULTS: According to the findings, it was found that six genes-AKR1B10, GNA15, ALDH1B1, PLOD2, LPCAT1, and GPX8- were differentially expressed in both TCGA-CSEC and GEO datasets among 23 differentially expressed metabolism-related genes (DEMRGs). mRNAsi exhibited a notable association with the extent of key oncogene mutation. The results showed that the AUC values for forecasting survival at 1, 3, and 5 years are 0.715, 0.689, and 0.748, individually. We observed a notable association between the risk score and different immune cell populations, along with enrichment in crucial signaling pathways in CESC. Four genes differentially expressed between different risk score groups were validated by IHC to be highly expressed in the CESC samples at the protein level. CONCLUSION: The current investigation indicated that a 3-gene signature based on stemness-related metabolic and 4 hub genes with differential expression between high and low-risk score subgroups may serve as valuable prognostic markers and potential therapeutic targets in CESC.

Dimerized sesquiterpenoid [4 + 2] adducts with ferroptosis-promoting activity from Inula britannica Linn.

Inubritanolides C and D (1 and 2), two exo sesquiterpenoid [4 + 2] adducts with unprecedented interconverting conformations of twist-chair and chair, together with two previously undescribed endo [4 + 2] dimers (3 and 4) were discovered from Inula britannica flowers. Dimers 1 and 2 have an undescribed carbon skeleton comprising of eudesmanolide and guaianolide units with the linkage mode of C-11/C-1' and C-13/C-3' via a Diels-Alder cycloaddition reaction. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, ECD, and variable-temperature NMR experiments. Dimer 2 displayed a strong inhibitory effect on breast cancer cells by promoting lipid ROS production, showing its potential as ferroptosis inducer.