Epigenetic regulation of FOXI2 promotes clear cell renal cell carcinoma progression.

In recent decades, substantial advancements in epigenetics have unveiled a profound understanding of its mechanisms in tumorigenesis and have offered promising strategies for epigenetic therapy in cancer patients. In our study, through bioinformatics analysis, we discovered a significant downregulation and hypermethylation of FOXI2 in clear cell renal cell carcinoma (ccRCC), while the expression in chromophobe cell carcinoma (chRCC) exhibited the opposite trend. Moreover, we established a strong correlation between FOXI2 expression levels and the prognosis of ccRCC. Gene enrichment analysis and cell function experiments unequivocally demonstrate that FOXI2 possesses the capability to induce cell cycle arrest and inhibit cell proliferation. Our research findings demonstrate that the expression of FOXI2 in ccRCC is under the regulation of promoter hypermethylation. Furthermore, in vitro experiments have conclusively shown that the overexpression of FOXI2 induces cell cycle arrest and inhibits cell proliferation.

Fusobacteria alterations are associated with colorectal cancer liver metastasis and a poor prognosis.

Liver metastasis is a major cause of mortality in patients with advanced stages of colorectal cancer (CRC). The gut microbiota has been demonstrated to influence the progression of liver diseases, potentially providing novel perspectives for diagnosis, treatment and research. However, the gut microbial characteristics in CRC with liver metastasis (LM) and with no liver metastasis (NLM) have not yet been fully established. In the present study, high-throughput 16S RNA sequencing technology was employed, in order to examine the gut microbial richness and composition in patients with CRC with LM or NLM. A discovery cohort (cohort 2; LM=18; NLM=36) and a validation cohort (cohort 3; LM=13; NLM=41) were established using fresh feces. In addition, primary carcinoma tissue samples were also analyzed (LM=8 and NLM=10) as a supplementary discovery cohort (cohort 1). The findings of the present study indicated that the intestinal microbiota richness and diversity were increased in the LM group as compared to the NLM group. A significant difference was observed in species composition between the LM and NLM group. In the two discovery cohorts with two different samples, the dominant phyla were consistent, but varied at lower taxonomic levels. Phylum Fusobacteria presented consistent and significant enrichment in LM group in both discovery cohorts. Furthermore, with the application of a random forest model and receiver operator characteristic curve analysis, Fusobacteria was identified as a potential biomarker for LM. Moreover, Fusobacteria was also a poor prognosis factor for survival. Importantly, the findings were reconfirmed in the validation cohort. On the whole, the findings of the present study demonstrated that CRC with LM and NLM exhibit distinct gut microbiota characteristics. Fusobacteria detection thus has potential for use in predicting LM and a poor prognosis of patients with CRC.

Correction: Effect of support on hydrogen generation over iron oxides in the chemical looping process.

[This corrects the article DOI: 10.1039/D1RA07210B.].

Mitochondrial dysfunction of peripheral blood mononuclear cells is associated with lung carcinogenesis.

The composition, quantity, and function of peripheral blood mononuclear cells (PBMCs) are closely correlated with tumorigenesis. However, the mechanisms of PBMCs in lung cancer are not clear. Mitochondria are energy factories of cells, and almost all cellular functions rely on their energy metabolism level. The present study aimed to test whether the mitochondrial function of PBMCs directly determines their tumor immune monitoring function. We recruited 211 subjects, including 105 healthy controls and 106 patients with recently diagnosed with lung cancer. The model of lung carcinogenesis induced by BaP was used in animal experiment, and the Bap carcinogenic metabolite, Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), was used in cell experiment. We found that mitochondrial function of PBMCs decreased significantly in patients with new lung cancer, regardless of age. In vivo, BaP caused PBMC mitochondrial dysfunction in mice before the appearance of visible malignant tissue. Moreover, mitochondrial function decreased significantly in mice with lung cancers induced by BaP compared to those without lung cancer after BaP intervention. In vitro, BPDE also induced mitochondrial dysfunction and reduced the aggressiveness of PBMCs toward cancer cells. Furthermore, the changes in mitochondrial energy metabolism gene expression caused by BPDE are involved in this process. Thus, the mitochondrial function of PBMCs is a potential prognostic biomarker or therapeutic target to improve clinical outcomes in patients with lung cancer.

Surgical treatment for right-side aortic arch concomitant with Kommerell's diverticulum: techniques selection and follow-up results.

BACKGROUND: Right-side aortic arch concomitant with Kommerell's diverticulum (KD) is a rare and complex ailment, and there is no consensus on the optimal strategy to deal with this congenital anomaly. We retrospectively analyzed and summary of the cases treated in our center with individual treatment methods for different situations. METHODS: Between September 2018 and December 2021, 10 patients experienced surgical therapy at our institution who presented with a Kommerell's diverticulum arising from an aberrant subclavian artery from the right-side aortic arch. Four main surgical techniques were applied to those patients: 1. total arch replacement with frozen elephant trunk implantation (n = 2); 2. hybrid procedure combining open arch repair and endovascular intervention (n = 1); 3. total endovascular repair using thoracic endovascular aortic repair (TEVAR) with or without left subclavian artery (LSCA) revascularization (n = 6); 4. direct repair underwent endoaneurysmorrhaphy. Clinical characteristics and outcomes were collected. RESULTS: The mean age of these 10 patients was 56.5 years (range 29-79 years) and only 1 woman. The pathology includes aortic dissection (n = 6) and aneurysm (n = 4). The mean diverticulum size was 41.4 [24.2-56.8] mm. There were no in-hospital deaths, and the median hospital stay was 22 [15-43] days. During the follow-up period (21.4 months, 1-44 months), one died of an unknown cause and one died of esophageal fistula. Two patients underwent second-stage endovascular intervention for distal lesion. And none of the patients had endoleak during the follow-up period. CONCLUSIONS: Each of the procedures we have mentioned here has its advantages and disadvantages; individualized treatment should meet the appropriate indications. A single-branched stent graft is feasible and effective in the treatment of aortic disease combined with Kommerell's diverticulum.

Effect of 10 Minutes of Prewarming and Prewarmed Intravenous Fluid Administration on the Core Temperature of Patients Undergoing Transurethral Surgery under General Anesthesia.

Background: Patients undergoing transurethral urologic procedures using bladder irrigation are at increased risk of perioperative hypothermia. Thirty minutes of prewarming prevents perioperative hypothermia. However, its routine application is impractical. We evaluated the effect of 10 minutes of prewarming combined with the intraoperative administration of warmed intravenous fluid on patients' core temperature. Methods: Fifty patients undergoing transurethral bladder or prostate resection under general anesthesia were included in this study and were randomly allocated to either the control group or the prewarming group. Patients in the prewarming group were warmed for 10 minutes before anesthesia induction with a forced-air warming device and received warmed intravenous fluid during operations. The patients in control group did not receive preoperative forced-air warming and were administered room-temperature fluid. Participants' core body temperature was measured on arrival at the preoperative holding area (T0), on entering the operating room, immediately after anesthesia induction, and in 10-minute intervals from then on until the end of the operation (Tend), on entering PACU, and in 10-minute intervals during the postanesthesia care unit stay. The groups' incidence of intraoperative hypothermia, change in core temperature (T0 - Tend), and postoperative thermal comfort were compared. Results: The incidence of hypothermia was 64% and 29% in the control group and prewarming group, respectively (P = 0.015). Change in core temperature was 0.93 ± 0.3 °C and 0.55 ± 0.4 °C in the control group and prewarming group, respectively (P = 0.0001). Thermal comfort was better in the prewarming group (P = 0.004). Conclusions: Ten minutes of prewarming combined with warmed intravenous fluid significantly decreased the incidence of intraoperative hypothermia and resulted in better thermal comfort in patients undergoing transurethral urologic surgery under general anesthesia.

Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy.

Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.

A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Computed Tomography Scan of the Aorta to Predict Type B Aortic Dissection.

BACKGROUND: The purpose of this study is to find the high-risk morphological features in type B aortic dissection (TBAD) population and to establish an early detection model. METHODS: From June 2018 to February 2022, 234 patients came to our hospital because of chest pain. After examination and definite diagnosis, we excluded people with previous cardiovascular surgery history, connective tissue disease, aortic arch variation, valve malformation, and traumatic dissection. Finally, we included 49 patients in the TBAD group and 57 in the control group. The imaging data were retrospectively analyzed by Endosize (Therevna 3.1.40) software. The aortic morphological parameters mainly include diameter, length, direct distance, and tortuosity index. Multivariable logistic regression models were performed and systolic blood pressure (SBP), aortic diameter at the left common carotid artery (D3), and length of ascending aorta (L1) were chosen to build a model. The predictive capacity of the models was evaluated through the receiver operating characteristic (ROC) curve analysis. RESULTS: The diameters in the ascending aorta and aortic arch are larger in the TBAD group (33.9 ± 5.9 vs. 37.8 ± 4.9 mm, p < 0.001; 28.2 ± 3.9 vs. 31.7 ± 3.0 mm, p < 0.001). The ascending aorta was significantly longer in the TBAD group (80.3 ± 11.7 vs. 92.3 ± 10.6 mm, p < 0.001). Besides, the direct distance and tortuosity index of the ascending aorta in the TBAD group increased significantly (69.8 ± 9.0 vs. 78.7 ± 8.8 mm, p < 0.001; 1.15 ± 0.05 vs. 1.17 ± 0.06, p < 0.05). Multivariable models demonstrated that SBP, aortic diameter at the left common carotid artery (D3), and length of ascending aorta (L1) were independent predictors of TBAD occurrence. Based on the ROC analysis, area under the ROC curve of the risk prediction models was 0.831. CONCLUSION: Morphological characteristic including diameter of total aorta, length of ascending aorta, direct distance of ascending aorta, and tortuosity index of ascending aorta are valuable geometric risk factors. Our model shows a good performance in predicting the incidence of TBAD.

Tumor-associated microbiota in colorectal cancer with vascular tumor thrombus and neural invasion and association with clinical prognosis.

Neural invasion (NI) and vascular tumor thrombus (VT) are associated with poor prognosis in patients with colorectal cancer (CRC). In this study, we apply 16S rRNA amplicon sequencing to tumor tissues and adjacent normal tissues in patients with CRC to determine the microbial differences. A discovery cohort, including 30 patients with NI, 23 with VT, and 35 with double-negative CRC tissue, is utilized. Then, we analyze the relationship between the specific bacterial taxa and indicators of different dimensions in separate cohorts. In the discovery cohort, the diversity and composition of the gut microbiome distinctly differ between the tumor and nontumor tissues in the NI and VT groups. A high abundance of Cupriavidus is found to be related to a short survival time of NI CRC, while Herbaspirillum is a potential microbial biomarker predicting the prognosis of patients with CRC with NI or VT. Moreover, the abundance of Cupriavidus or Herbaspirillum is associated with some clinical patient characteristics and prognosis, respectively. In conclusion, this study is the first to comprehensively elaborate the differences in the gut microbiota of patients with CRC with different invasion statuses and to prove the relationship between some gut microbiota and clinical patient characteristics.

Exploring Potential Biomarkers of Early Thymoma based on Serum Proteomics.

BACKGROUND: Early diagnosis remains difficult because the early symptoms of thymoma are atypical. OBJECTIVES: This study aimed to analyze the changes of serum proteins in the early stage of thymoma (stage I/II) by proteomics method and to screen and validate candidate biomarkers. METHODS: Proteins were extracted from 8 sera patients with stage I/II thymoma and 9 healthy controls. The levels of serum proteins were detected by data-independent acquisition (DIA) quantitative proteomics techniques, and the differential proteins were identified. The proteomic results were verified by enzyme-linked immunosorbent assay. Additionally, differentially expressed proteins were analyzed using receiver operating characteristic curves (ROC). RESULTS: There were 80 differentially expressed proteins between the patients with thymoma and the healthy control group, among which 39 were up-regulated and 41 were down-regulated. Differential protein enrichment is involved in environmental information processing, signaling molecules and interactions, and in the body system and the immune system. The analysis of receptor working characteristic curves showed that the areas under the curve of CORO1A, SAA1 and LTA4H were all larger than 0.8, indicating that these proteins had good diagnostic value. CONCLUSION: CORO1A, SAA1 and LTA4H may be new biomarkers for early screening of thymoma.

An engineered lymph node comprising porous collagen scaffold with hybridized biological signals embedded in B cell membrane coatings.

Complications can arise from damaging or removing lymph nodes after surgeries for malignant tumours. Our team has developed an innovative solution to recreate lymph nodes via an engineering approach. Using a Type II collagen scaffold coated with B cell membranes for the sake of attracting T cells in different regions, we could mimic the thymus-dependent and thymus-independent areas in vitro. This engineering strategy based on biophysical mimicry has a great potential for clinical applications. By further conjugating biological signals, anti-CD3/28, onto the scaffold coated with the B cell membrane, we achieved an 11.6-fold expansion of T cells within 14 days of in vitro culture while ensuring their activity, phenotype homeostasis, and differentiation capacity kept intact. Artificial lymph nodes had excellent biocompatibility and caused no pathological or physiological adverse effects after implantation into C57BL6 mice. In vivo assays also demonstrated that this artificial lymph node system positively adhered to omental tissues, creating an environment that fostered T cell growth and prevented cellular failure and death. Additionally, it induced vascular and lymphatic vessel invasion, which was beneficial to the migration and circulation of T cells between this system and peripheral blood. Due to the porous collagen fibre structure, it also facilitated the infiltration of host immune cells. This work opens new avenues to immune organ regeneration via a tissue engineering approach.

Fluorescence-guided colorectal surgery: applications, clinical results, and protocols.

In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750-800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG's role, advantages, disadvantages, and potential clinical impact in colorectal surgery.

Changes in Bacteroides and the microbiota in patients with obstructed colorectal cancer: retrospective cohort study.

BACKGROUND: The relationship between intestinal obstruction due to colorectal cancer (CRC) and the gut microbiota remains largely unknown. The aim of this study was to investigate the potential association between alterations in gut microbiota and CRC in the presence of intestinal obstruction. METHODS: Patients with CRC with or without obstruction were recruited and compared using 1:1 propensity score matching (PSM). Total DNA from tumours and adjacent normal tissues of 84 patients and 36 frozen tumour tissues was extracted and amplified. 16S RNA sequencing was used to uncover differences in microbiota composition between the two groups. RESULTS: A total of 313 patients with CRC were recruited. Survival analysis demonstrated that patients in the obstruction group had shorter overall survival time and disease-free survival (DFS) time than those in the non-obstruction group. Microbial richness and diversity in tumour tissues of patients with obstruction were significantly higher than those of patients with no obstruction. The alpha diversity indices and beta diversity exhibited were different between the two groups (P < 0.05). At the phylum and genus levels, Bacteroidetes were significantly enriched in the tumour tissues of patients with obstruction. Alpha diversity in tumour tissues was closely related to specific microbiota. These findings were replicated in the 16S rRNA analyses from frozen samples. There were more Bacteroidetes in CRC patients with obstruction. CONCLUSIONS: Patients with obstructed CRC have worse prognosis and have differences in their microbiota. Higher levels of Bacteroides were observed in patients with obstructed CRC.

The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer.

BACKGROUND: This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). METHODS: The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings. RESULTS: All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p < 0.001). Furthermore, the ICIS-H group was additionally associated with a longer PFS (p < 0.001) and overall survival (OS; p = 0.001), at significant levels. In the multivariate analysis, both TCIS-H and ICIS-H groups were identified as independent predictors of favorable PFS (p = 0.012 and p = 0.001, respectively). ICIS-H was also shown to be an independent predictor of favorable OS (p = 0.003). The analysis of the mRNA expression data from TCGA also validated our findings regarding TNBC. CONCLUSION: Our novel TCIS and ICIS exhibited a significant prognostic value in TNBC. Additional research would be needed to strengthen our findings and identify the most efficient prognostic and predictive biomarkers for TNBC patients.

Molecular cloning and characterization of endoplasmic reticulum stress related genes grp78 and atf6α from black seabream (Acanthopagrus schlegelii) and their expressions in response to nutritional regulation.

Glucose-regulated protein 78 (grp78) and activating transcription factor 6α (atf6α) are considered vital endoplasmic reticulum (ER) molecular chaperones and ER stress (ERS) sensors, respectively. In the present study, the full cDNA sequences of these two ERS-related genes were first cloned and characterized from black seabream (Acanthopagrus schlegelii). The grp78 cDNA sequence is 2606 base pair (bp) encoding a protein of 654 amino acids (aa). The atf6α cDNA sequence is 2168 base pair (bp) encoding a protein of 645 aa. The predicted aa sequences of A. schlegelii grp78 and atf6α indicated that the proteins contain all the structural features, which were characteristic of the two genes in other species. Tissues transcript abundance analysis revealed that the mRNAs of grp78 and atf6α were expressed in all measured tissues, but the highest expression of these two genes was all recorded in the gill followed by liver/ brain. Moreover, in vivo experiment found that fish intake of a high lipid diet (HLD) can trigger ERS by activating grp78/Grp78 and atf6α/Atf6α. However, it can be alleviated by dietary betaine supplementation, similar results were also obtained by in vitro experiment using primary hepatocytes of A. schlegelii. These findings will be beneficial for us to evaluate the regulator effects of HLD supplemented with betaine on ERS at the molecular level, and thus provide some novel insights into the functions of betaine in marine fish fed with an HLD.

Short-term outcomes of da Vinci SP versus Xi for colon cancer surgery: a propensity-score matching analysis of multicenter cohorts.

Recent advancements in robotic systems have led to the introduction of the da Vinci SP system, which allows surgeons to perform colon cancer surgery through fewer ports. This study aimed to evaluate the perioperative outcomes of colon cancer surgeries conducted using the da Vinci SP and Xi systems. Patients who underwent robotic colon cancer surgeries between November 2020 and December 2022 at two tertiary referral centers were considered for inclusion. Following propensity-score matching, short-term outcomes between the two systems were retrospectively analyzed. Out of 189 patients included in the study, 106 from 53 propensity-score matched pairs were analyzed. Patients operated on with the SP system exhibited smaller incision lengths (5.0 cm vs. 9.4 cm, p < 0.001) experienced less pain at 8 h (3.0 vs. 3.5, p < 0.001) and at 24 h post-operation (2.9 vs. 3.3, p = 0.001) and had a shorter duration of hospital stay (5 days vs. 6 days, p = 0.002). The overall rate of postoperative complications was 10.4%, with no significant difference between the SP and Xi groups (7.5% vs. 13.2%). Robotic-assisted colon cancer surgery using the da Vinci SP system is feasible and demonstrates favorable short-term outcomes. Compared to the Xi system, the SP system offers advantages in terms of cosmesis, postoperative pain, and recovery duration for colon cancer patients.

Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration.

MAP4K1 has been identified as a cancer immunotherapy target. Whether and how cancer cell-intrinsic MAP4K1 contributes to glioblastoma multiforme (GBM) progression remains unclear. We found that MAP4K1 was highly expressed in the glioma cells of human GBM specimens. High levels of MAP4K1 mRNA were prevalent in IDH-WT and 1p/19q non-codeletion gliomas and correlated with poor prognosis of patients. MAP4K1 silencing inhibited GBM cell proliferation and glioma growth. Transcriptome analysis of GBM cells and patient samples showed that MAP4K1 modulated cytokine‒cytokine receptor interactions and chemokine signaling pathway, including IL-18R and IL-6R Importantly, MAP4K1 loss down-regulated membrane-bound IL-18R/IL-6R by inhibiting the PI3K-AKT pathway, whereas MAP4K1 restoration rescued this phenotype and therefore GBM cell proliferation. MAP4K1 deficiency abolished GBM cell pro-proliferation responses to IL-18, suggesting an oncogenic role of MAP4K1 via the intrinsic IL-18/IL-18R pathway. In addition, GBM cell-derived MAP4K1 impaired T-cell migration and reduced CD8+ T-cell infiltration in mouse glioma models. Together, our findings provide novel insight into the pathological significance of GBM cell-intrinsic MAP4K1 in driving tumor growth and immune evasion by remodeling cytokine-chemokine networks.

Beauvericin exerts an anti-tumor effect on hepatocellular carcinoma by inducing PI3K/AKT-mediated apoptosis.

Beauvericin is a world-spread mycotoxin isolated from the traditional Chinese medicine, Bombyx batryticatus (BB), which has been widely used to treat various neoplastic diseases. This study investigated the anti-hepatocellular carcinoma (HCC) activity of beauvericin and its potential mechanism. In this study, H22-bearing mice were intraperitoneally injected with 3, 5, 7 mg/kg of beauvericin once per-week over a three-week period. TUNEL staining determined the extent of tumor apoptosis induced by beauvericin. ELISA kits detected the level of IL-2, Perforin, and TNF-α, IFN-γ level in the serum. H22 hepatoma cells were exposed to beauvericin (5, 10, and 20 µmol/L) to investigate the underlying pathway. CCK-8 assay was used to observe the influence of beauvericin on the growth of H22 cells. Flow cytometry was used to detect the cell apoptosis and ROS level. Western blotting was performed to detect apoptotic and PI3K/AKT pathway protein production. The results showed that beauvericin could remarkably inhibit the growth of HCC in mice, combined with elevated TNF-α and IL-2. In vitro, beauvericin significantly promoted the generation of ROS, up-regulated Bax/Bcl-2 ratio and cleaved caspase-9, cleaved caspase-3 levels, down-regulated p-PI3K/PI3K ratio, p-AKT/AKT ratio, promoted the apoptosis of H22 cells, and inhibited the growth of H22 cells. Remarkably, treatment with PI3K/AKT activator (740Y-P and SC79) could prevent beauvericin-induced H22 cell apoptosis. These findings collectively indicate that beauvericin inhibits HCC growth by inducing apoptosis via the PI3K/AKT pathway.

Catechin-Functionalized Cationic Lipopolymer Based Multicomponent Nanomicelles for Lung-Targeting Delivery.

Catechins from green tea are one of the most effective natural compounds for cancer chemoprevention and have attracted extensive research. Cancer cell-selective apoptosis-inducing properties of catechins depend on efficient intracellular delivery. However, the low bioavailability limits the application of catechins. Herein, a nano-scaled micellar composite composed of catechin-functionalized cationic lipopolymer and serum albumin is constructed. Cationic liposomes tend to accumulate in the pulmonary microvasculature due to electrostatic effects and are able to deliver the micellar system intracellularly, thus improving the bioavailability of catechins. Albumin in the system acts as a biocompatible anti-plasma absorbent, forming complexes with positively charged lipopolymer under electrostatic interactions, contributing to prolonged in vivo retention. The physicochemical properties of the nano-micellar complexes are characterized, and the antitumor properties of catechin-functionalized materials are confirmed by reactive oxygen species (ROS), caspase-3, and cell apoptosis measurements. The role of each functional module, cationic polymeric liposome, and albumin is revealed by cell penetration, in vivo animal assays, etc. This multicomponent micellar nanocomposite has the potential to become an effective vehicle for the treatment of lung diseases such as pneumonia, lung tumors, sepsis-induced lung injury, etc. This study also demonstrates that it is a great strategy to create a delivery system that is both tissue-targeted and biologically active by combining cationic liposomes with the native bioactive compound catechins.