Glycated walnut meal peptide­calcium chelates (COS-MMGGED-Ca): Preparation, characterization, and calcium absorption-promoting.

This study isolated a novel peptide MMGGED with strong calcium-binding capacity from defatted walnut meal and synthesized a novel peptide­calcium chelate COS-MMGGED-Ca with high stability via glycation. Structural characterization and computer simulation identified binding sites, while in vitro digestion stability and calcium transport experiments explored the chelate's properties. Results showed that after glycation, COS-MMGGED bound Ca2+ with 88.75 ± 1.75 %, mainly via aspartic and glutamic acids. COS-MMGGED-Ca released Ca2+ steadily (60.27 %), with thermal denaturation temperature increased by 18 °C and 37 °C compared to MMGGED-Ca, indicating good processing performance. Furthermore, COS-MMGGED significantly enhanced Ca2+ transport across Caco-2 monolayers, 1.13-fold and 1.62-fold higher than CaCl2 and MMGGED, respectively, at 240 h. These findings prove glycation enhances structural properties, stability, calcium loading, and transport of peptide­calcium chelates, providing a scientific basis for developing novel efficient calcium supplements and high-value utilization of walnut meal.

Effect of Small Doses of Azithromycin on Pulmonary Ventilation Function and Inflammatory Factors IL-6, IL-13 in Children with Bronchial Asthma.

OBJECTIVE: To observe the effect of low-dose azithromycin on pulmonary ventilation function and inflammatory factors IL-6, IL-13 in children with bronchial asthma. METHODS: A total of 80 children with asthma in Pediatric Medicine affiliated to Taizhou Women and Children's Hospital of Wenzhou Medical University from January 2019 to December 2022 were selected and divided into control group (42 cases) and study group (38 cases). The control group regularly inhaled Salmeterol Xinafoate and Fluticasone Propionate inhalation, while the study group was additionally given low-dose azithromycin. After four weeks of treatment, pulmonary function tests including FEV1, FVC were performed and inflammatory indicators including CRP, FeNO, IL-6, IL-13 were measured. The occurrence of adverse reactions during treatment was recorded. RESULTS: Pulmonary function tests including FEV1%, FEV1/FVC% were improved in all subjects, and the improvement of pulmonary function was more significant in the study group (P<0.05). The levels of CRP, FeNO, IL-6 and IL-13 were decreased in the two groups, especially in the study group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05). CONCLUSION: Low-dose azithromycin can significantly improve the pulmonary function in children with bronchial asthma, reduce the levels of inflammatory factors, control airway mucus secretion and inflammation, and can be used to treat chronic lung diseases such as bronchial asthma.

Inhibitory receptors and checkpoints on NK cells: Implications for cancer immunotherapy.

With the success of immunosuppressive checkpoint in tumor therapy, the corresponding adverse response and drug resistance defects have been exposed. T cells and NK cells are the body's immune system of the two substantial main forces. in recent years, study of T cell checkpoints appeared a certain block, such as PD-1 the effect not benign, on the distribution of NK cell surface excitatory and inhibitory receptors under normal conditions to maintain steady, could be targeted in the tumor treatment blockade have therapeutic effect. This paper reviews the function of NK cells and the effects of corresponding receptors in various types of tumors, providing a direction for the selection of appropriate gate control sites for future treatment.

Myeloid-derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in cancer.

Myeloid-derived suppressor cell (MDSC) mainly exists in tumor microenvironment (TME) and interferes with normal immune response of the body. These immature differentiated cells cooperate with tumor cells for immune escape and proliferation. The subtypes of MDSC are different in different organisms, and STAT become a high priority for the signaling pathway mediating the regulation of MDSC. The surface of MDSC cell population contains a variety of signal molecular receptors, and its differentiation degree is toilless to be chemotaxis by different factors. The role of MDSC in silencing T cells and promoting regulatory T cells (Treg) is particularly significant. This review mainly contains the origin of MDSC, the characteristics of subgroups, the focus of the study on MDSC heat molecules and signaling pathways, the relationship between MDSC and carcinoma, prognosis and hope to propose an overview of current MDSCs- targeting therapies so as to provide new ideas for cancer treatment.

The Mechanism of Peach Gum Polysaccharide Preventing UVB-Induced Skin Photoaging by Regulating Matrix Metalloproteinanse and Oxidative Factors.

Exposure to ultraviolet light can cause oxidative damage and accelerate skin aging and is one of the main causes of skin aging. Peach gum polysaccharide (PG) is a natural edible plant component that has many biological activities, such as regulating blood glucose and blood lipids and improving colitis, as well as antioxidant and anticancer properties. However, there are few reports on the antiphotoaging effect of peach gum polysaccharide. Therefore, in this paper, we study the basic composition of the raw material peach gum polysaccharide and its ability to improve UVB-induced skin photoaging damage in vivo and in vitro. The results show that peach gum polysaccharide is mainly composed of mannose, glucuronic acid, galactose, xylose, and arabinose, and its molecular weight (Mw) is 4.10 × 106 g/mol. The results of the in vitro cell experiments show that PG could significantly alleviate UVB-induced apoptosis of human skin keratinocytes, promote cell growth repair, reduce the expression of intracellular oxidative factors and matrix metal collagenase, and improve the extent of oxidative stress repair. Moreover, the results from the in vivo animal experiments showed that PG could not only effectively improve the phenotype of UVB-induced photoaged skin in model mice but also significantly improve their oxidative stress status, regulate the contents of ROS and the levels of SOD and CAT, and repair the oxidative skin damage induced by UVB in vivo. In addition, PG improved UVB-induced photoaging-mediated collagen degradation in mice by inhibiting the secretion of matrix metalloproteinases. The above results indicate that peach gum polysaccharide has the ability to repair UVB-induced photoaging and may be used as a potential drug and antioxidant functional food to resist photoaging in the future.

USP18 regulates the malignant phenotypes of glioblastoma stem cells.

Glioblastoma (GBM) is the most malignant primary brain tumor. The 5-year survival rate of the patients is poor, and they are prone to relapse and the treatment is limited. Therefore, the search for biological targets is one of the key measures for the treatment and prognosis of GBM. Ubiquitin-specific peptidase 18 (USP18) plays a regulatory role in tumorigenesis. In this study, we found that USP18 was up-regulated in GBM, promoted the growth and proliferation of glioblastoma stem cells (GSCs), affected the epithelial-mesenchymal transition (EMT), and was associated with poor clinical prognosis of patients. Finally, our findings reveal a critical role for USP18 in GBM malignancy, targeting USP18 may open new avenues for GBM treatment.

In vivo overexpression of synaptogyrin-3 promotes striatal synaptic dopamine uptake in LRRK2R1441G mutant mouse model of Parkinson's disease.

BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) mutation is a common genetic risk factor of Parkinson's disease (PD). Presynaptic dysfunction is an early pathogenic event associated with dopamine (DA) dysregulation in striatum of the brain. DA uptake activity of DA uptake transporter (DAT) affects synaptic plasticity and motor and non-motor behavior. Synaptogyrin-3 (SYNGR3) is part of the synaptogyrin family, especially abundant in brain. Previous in vitro studies demonstrated interaction between SYNGR3 and DAT. Reduced SYNGR3 expression was observed in human PD brains with unclear reasons. METHODS: Here, we further explored whether inducing SYNGR3 expression can influence (i) cellular DA uptake using differentiated human SH-SY5Y neuronal cells, (ii) striatal synaptosomal DA uptake in a mutant LRRK2R1441G  knockin mouse model of PD, and (iii) innate rodent behavior using the marble burying test. RESULTS: Young LRRK2 mutant mice exhibited significantly lower SYNGR3 levels in striatum compared to age-matched wild-type (WT) controls, resembling level in aged WT mice. SYNGR3 is spatially co-localized with DAT at striatal presynaptic terminals, visualized by immuno-gold transmission electron microscopy and immunohistochemistry. Their protein-protein interaction was confirmed by co-immunoprecipitation. Transient overexpression of SYNGR3 in differentiated SH-SY5Y cells increased cellular DA uptake activity without affecting total DAT levels. Inducing SYNGR3 overexpression by adeno-associated virus-7 (AAV7) injection in vivo into striatum increased ex vivo synaptosomal DA uptake in LRRK2 mutant mice and improved their innate marble burying behavior. CONCLUSION: Brain SYNGR3 expression may be an important determinant to striatal DA homeostasis and synaptic function. Our preliminary behavioral test showed improved innate behavior after SYNGR3 overexpression in LRRK2 mutant mice, advocating further studies to determine the influence of SYNGR3 in the pathophysiology of DA neurons in PD.

ZIC5 promotes aggressiveness and cancer stemness in cervical squamous cell carcinoma.

BACKGROUND: Cervical cancer is one of the major malignancies causing morbidity and mortality in women in developing countries. ZIC5 has been found to be associated with a variety of cancers, yet the expression and molecular function of ZIC5 in cervical squamous cell carcinoma (CESC) is unknown. METHODS: We examined the expression of ZIC5 in tumors and normal tissues of CESC patients using immunohistochemistry, immunoblotting and fluorescent quantitative PCR, and used statistical methods to explore its relationship with clinical manifestations. Next, we constructed ZIC5 knockdown and overexpression CESC cell lines to observe the effect of ZIC5 on the proliferation and metastasis of CESC cells. Finally, we applied a nude mouse xenograft tumor model to observe the effect of ZIC5 on tumorigenesis in vivo. RESULTS: Our results showed that the expression of ZIC5 was higher in cancer tissues than in normal tissues. Prognostic analysis showed that ZIC5 expression level was an independent prognostic factor in CESC patients, and the results of Transwell, CCK-8 and wound healing assays confirmed that overexpression of ZIC5 could promote the proliferation and migration of CESC cells. A nude mouse xenograft tumor model showed that knockdown of ZIC5 inhibited tumor growth in vivo. Database, immunoblotting assay and in vitro sphere-forming assay confirmed that ZIC5 could promote the stemness of CESC cells. CONCLUSION: ZIC5 is a factor that indicates a poor prognosis of CESC patients and promotes stemness in CESC cells. ZIC5 may be a potential biomarker and therapeutic target for CESC patients.

ALA-PDT regulates macrophage M1 polarization via ERK/MAPK-NLRP3 pathway to promote the early inflammatory response.

BACKGROUND: Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. METHODS: In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg-1), CD206, iNOS, CD86, and inflammatory factors IL-6, TNF-α, and IL-1ß by reverse transcription-polymerase chain reaction and Western blot, Milliplex microtubule-associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and NOD-like receptor protein 3 (NLRP3) inflammasome. RESULTS: 5-Aminolevulinic acid (ALA)-PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg-1/CD206 in RAW264.7 cells, while, proinflammatory factors IL-6, TNF-α, and IL-1ß expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK-NLRP3 pathway. CONCLUSION: ALA-PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK-NLRP3 pathway. It also promotes macrophage phagocytosis.

The cancer-testis antigen FBXO39 predicts poor prognosis and is associated with stemness and aggressiveness in glioma.

Gliomas are common brain tumors with poor prognosis. F-box protein39 (FBXO39) is found to be increased in a variety of malignancies, but its expression in gliomas is unknown. Here, we report that FBXO39 as an oncogene is upregulated in glioma and associated with poor prognosis. The degree of FBXO39 positive expression is doubtlessly concomitant with the grade of glioma. The data analyses show that patients with high FBXO39 expression have poor overall survival. What's more, FBXO39 accelerates the invasion and migration abilities of glioma cells and promotes glioma stem cell growth and stemness. In summary, these results suggest that FBXO39 is expected to become a new biological target for judging the prognosis and treatment of glioma.

FBXO39 predicts poor prognosis and correlates with tumor progression in cervical squamous cell carcinoma.

BACKGROUND: Cancer/testis antigen (CTA) is a class of antigen molecules mainly expressed in the germinal epithelium of testis and some tumor tissues. FBXO39, also known as F-box protein 39, is a crucial CTA molecule. F-box protein 39 (FBXO39) is overexpressed in cervical squamous cell carcinomas (CESCs), however its function in cancer development and clinical significance are still unknown. METHODS: We used paraffin-embedded tumor tissues from 124 patients and fresh-harvested and paired adjacent normal esophageal tissues from 15 CESC patients who underwent primary surgical resection in Xijing Hospital between 2015 and 2020. The expression level of FBXO39 was evaluated through immunohistochemistry, Western Blot and q-PCR. Prognostic and survival analyses were conducted using univariate/multivariate analysis and log-rank analysis with SPSS 23.0. CCK-8, wound-healing and Transwell assays were applied to demonstrate that FBXO39 promoted the proliferation, migration and invasion. Finally, we constructed a xenografts model of the C-33A cell lines to observe the effect of FBXO39 on tumorigenesis in vivo. RESULTS: Immunohistochemical results showed that FBXO39 was highly expressed in cancer tissues than in corresponding non-cancer tissues. Similarly, we proved this result at protein and mRNA level by Western-Blotting and q-PCR. Prognostic and OS analyses showed that the FBXO39 expression level was an individual prognostic factor in CESC patients. CCK-8, wound-healing and Transwell assays proved that the overexpression of FBXO39 in Si-Ha cells promoted the proliferation, migration and invasion of the cells. Knocking down FBXO39 in C-33A cells inhibited the proliferation, migration and invasion of cells. The experimental results of xenografts model in nude mice showed that the knockdown of FBXO39 in C-33A cells slowed down the growth of tumor. CONCLUSION: FBXO39 is a poor prognostic factor of cervical squamous cell carcinoma, which may provide a novel therapeutic target for CESC.

Recent developments in Moringa oleifera Lam. polysaccharides: A review of the relationship between extraction methods, structural characteristics and functional activities.

Moringa oleifera Lam. (M. oleifera Lam) is a perennial tropical deciduous tree that belongs to the Moringaceae family. Polysaccharides are one of the major bioactive compounds in M. oleifera Lam and show immunomodulatory, anticancer, antioxidant, intestinal health protection and antidiabetic activities. At present, the structure and functional activities of M. oleifera Lam polysaccharides (MOPs) have been widespread, but the research data are relatively scattered. Moreover, the relationship between the structure and biological activities of MOPs has not been summarized. In this review, the current research on the extraction, purification, structural characteristics and biological activities of polysaccharides from different sources of M. oleifera Lam were summarized, and the structural characteristics of purified polysaccharides were focused on this review. Meanwhile, the biological activities of MOPs were introduced, and some molecular mechanisms were listed. In addition, the relationship between the structure and biological activities of MOPs was discussed. Furthermore, new perspectives and some future research of M. oleifera Lam polysaccharides were proposed in this review.

Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its Expression.

Synaptogyrin-3 (SYNGR3) is a synaptic vesicular membrane protein. Amongst four homologues (SYNGR1 to 4), SYNGR1 and 3 are especially abundant in the brain. SYNGR3 interacts with the dopamine transporter (DAT) to facilitate dopamine (DA) uptake and synaptic DA turnover in dopaminergic transmission. Perturbed SYNGR3 expression is observed in Parkinson's disease (PD). The regulatory elements which affect SYNGR3 expression are unknown. Nuclear-receptor-related-1 protein (NURR1) can regulate dopaminergic neuronal differentiation and maintenance via binding to NGFI-B response elements (NBRE). We explored whether NURR1 can regulate SYNGR3 expression using an in silico analysis of the 5'-flanking region of the human SYNGR3 gene, reporter gene activity and an electrophoretic mobility shift assay (EMSA) of potential cis-acting sites. In silico analysis of two genomic DNA segments (1870 bp 5'-flanking region and 1870 + 159 bp of first exon) revealed one X Core Promoter Element 1 (XCPE1), two SP1, and three potential non-canonical NBRE response elements (ncNBRE) but no CAAT or TATA box. The longer segment exhibited gene promoter activity in luciferase reporter assays. Site-directed mutagenesis of XCPE1 decreased promoter activity in human neuroblastoma SH-SY5Y (↓43.2%) and human embryonic kidney HEK293 cells (↓39.7%). EMSA demonstrated NURR1 binding to these three ncNBRE. Site-directed mutagenesis of these ncNBRE reduced promoter activity by 11-17% in SH-SY5Y (neuronal) but not in HEK293 (non-neuronal) cells. C-DIM12 (Nurr1 activator) increased SYNGR3 protein expression in SH-SY5Y cells and its promoter activity using a real-time luciferase assay. As perturbed vesicular function is a feature of major neurodegenerative diseases, inducing SYNGR3 expression by NURR1 activators may be a potential therapeutic target to attenuate synaptic dysfunction in PD.

Characterization of the structure, stability, and activity of hypoglycemic peptides from Moringa oleifera seed protein hydrolysates.

Moringa oleifera seed protein hydrolysates exhibit good hypoglycemic activity, but their specific peptide components have not yet been characterized. Here, we identified the ultrafiltration peptide components (<3 kDa) of M. oleifera seed protein hydrolysates. A highly active α-glucosidase inhibitory peptide with an IC50 value of 109.65 µM (MoHpP-2) with the amino acid sequence KETTTIVR was identified. We characterized its structural properties, stability, and hypoglycemic activity. MoHpP-2 was found to be an amphipathic peptide with a ß-turn structure, and the hemolysis of red blood cells was not observed when its concentration was lower than 2 mg mL-1. MoHpP-2 was stable under weakly acidic conditions, at temperatures lower than 60 °C, and at high ion concentrations. Western blotting revealed that MoHpP-2 affected the PI3K and AMPK pathways of HepG2 cells. Molecular docking revealed that MoHpP-2 interacted with α-glucosidase through hydrogen bonding and hydrophobic forces. Thus, MoHpP-2 from M. oleifera seeds could be used to make hypoglycemic functional foods.

Protective effects of non-extractable phenolics from strawberry against inflammation and colon cancer in vitro.

Strawberry is a rich source of phenolics. However, most studies focused on extractable phenolics (EP) while neglecting non-extractable phenolics (NEP). The aim of this study was to characterize EP and NEP from strawberry (Fragaria × ananassa) and determine their anti-inflammatory and anti-colon cancer potentials in cell culture models. NEP contained flavonols, flavanols and phenolic acids that were released through alkaline hydrolysis. NEP dose-dependently inhibited lipopolysaccharides -induced NO production in RAW 264.7 macrophage. Western blotting showed that NEP reduced the expression levels of pro-inflammatory proteins such as iNOS and c-FOS, but increased the expression level of antioxidative protein, such as HO-1. Moreover, NEP markedly suppressed proliferation of human colon cancer HCT116 cells via inducing G2/M phase cell cycle arrest and apoptosis. Collectively, these findings illustrated preventive effects of strawberry NEP against inflammation and colon cancer, shedding light on potential contribution of NEP from strawberry as a health-promoting agent.

Short-Chain Fatty Acids Produced by Ruminococcaceae Mediate α-Linolenic Acid Promote Intestinal Stem Cells Proliferation.

SCOPE: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α-linolenic acid (ALA) has seldom been reported. METHODS AND RESULTS: After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg-1 ) promotes small intestinal and villus growth by activating the Wnt/ß-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. CONCLUSION: These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/ß-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.

The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation.

Formyl peptide receptors (FPRs) are a group of G protein-coupled cell surface receptors that play important roles in host defense and inflammation. Owing to the ubiquitous expression of FPRs throughout different cell types and since they interact with structurally diverse chemotactic agonists, they have a dual function in inflammatory processes, depending on binding with different ligands so that accelerate or inhibit key intracellular kinase-based regulatory pathways. Neuroinflammation is closely associated with the pathogenesis of neurodegenerative diseases, neurogenic tumors and cerebrovascular diseases. From recent studies, it is clear that FPRs are important biomarkers for neurological diseases as they regulate inflammatory responses by monitoring glial activation, accelerating neural differentiation, regulating angiogenesis, and controlling blood brain barrier (BBB) permeability, thereby affecting neurological disease progression. Given the complex mechanisms of neurological diseases and the difficulty of healing, we are eager to find new and effective therapeutic targets. Here, we review recent research about various mechanisms of the effects generated after FPR binding to different ligands, role of FPRs in neuroinflammation as well as the development and prognosis of neurological diseases. We summarize that the FPR family has dual inflammatory functional properties in central nervous system. Emphasizing that FPR2 acts as a key molecule that mediates the active resolution of inflammation, which binds with corresponding receptors to reduce the expression and activation of pro-inflammatory composition, govern the transport of immune cells to inflammatory tissues, and restore the integrity of the BBB. Concurrently, FPR1 is essentially related to angiogenesis, cell proliferation and neurogenesis. Thus, treatment with FPRs-modulation may be effective for neurological diseases.

Opportunities and challenges of glioma organoids.

Glioma is the most common primary brain tumor and its prognosis is poor. Despite surgical removal, glioma is still prone to recurrence because it grows rapidly in the brain, is resistant to chemotherapy, and is highly aggressive. Therefore, there is an urgent need for a platform to study the cell dynamics of gliomas in order to discover the characteristics of the disease and develop more effective treatments. Although 2D cell models and animal models in previous studies have provided great help for our research, they also have many defects. Recently, scientific researchers have constructed a 3D structure called Organoids, which is similar to the structure of human tissues and organs. Organoids can perfectly compensate for the shortcomings of previous glioma models and are currently the most suitable research platform for glioma research. Therefore, we review the three methods currently used to establish glioma organoids. And introduced how they play a role in the diagnosis and treatment of glioma. Finally, we also summarized the current bottlenecks and difficulties encountered by glioma organoids, and the current efforts to solve these difficulties. Video Abstract.

Microtubule associated protein 4 (MAP4) phosphorylation reduces cardiac microvascular density through NLRP3-related pyroptosis.

Phosphorylation of MAP4 (p-MAP4) causes cardiac remodeling, with the cardiac microvascular endothelium being considered a vital mediator of this process. In the current study, we investigated the mechanism underlying p-MAP4 influences on cardiac microvascular density. We firstly confirmed elevated MAP4 phosphorylation in the myocardium of MAP4 knock-in (KI) mice. When compared with the corresponding control group, we detected the decreased expression of CD31, CD34, VEGFA, VEGFR2, ANG2, and TIE2 in the myocardium of MAP4 KI mice, accompanied by a reduced plasma concentration of VEGF. Moreover, we observed apoptosis and mitochondrial disruption in the cardiac microvascular endothelium of MAP4 KI animals. Consistently, we noted a decreased cardiac microvascular density, measured by CD31 and lectin staining, in MAP4 KI mice. To explore the underlying mechanism, we targeted the NLRP3-related pyroptosis and found increased expression of the corresponding proteins, including NLRP3, ASC, mature IL-1ß, IL-18, and GSDMD-N in the myocardium of MAP4 KI mice. Furthermore, we utilized a MAP4 (Glu) adenovirus to mimic cellular p-MAP4. After incubating HUVECs with MAP4 (Glu) adenovirus, the angiogenic ability was inhibited, and NLRP3-related pyroptosis were significantly activated. Moreover, both cytotoxicity and PI signal were upregulated by the MAP4 (Glu) adenovirus. Finally, NLRP3 inflammasome blockage alleviated the inhibited angiogenic ability induced by MAP4 (Glu) adenovirus. These results demonstrated that p-MAP4 reduced cardiac microvascular density by activating NLRP3-related pyroptosis in both young and aged mice. We thus managed to provide clues explaining MAP4 phosphorylation-induced cardiac remodeling and enriched current knowledge regarding the role of MAP4.

Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway.

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.