Preparation, structural characterization, bioactivities, and applications of Crataegus spp. polysaccharides: A review.

Crataegus, is a genus within the Rosaceae family. It is recognized as a valuable plant with both medicinal and edible qualities, earning it the epithet of the "nutritious fruit" owing to its abundant bioactive compounds. Polysaccharides are carbohydrate polymers linked by glycosidic bonds, one of the crucial bioactive ingredients of Crataegus spp. Recently, Crataegus spp. polysaccharides (CPs) have garnered considerable attention due to their diverse range of bioactivities, including prebiotic, hypolipidemic, anticancer, antibacterial, antioxidant, and immunobiological properties. Herein, we provide a comprehensive overview of recent research on CPs. The analysis revealed that CPs exhibited a broad molecular weight distribution, ranging from 5.70 Da to 4.76 × 108 Da, and are composed of various monosaccharide constituents such as mannose, rhamnose, and arabinose. Structure-activity relationships demonstrated that the biological function of CPs is closely associated with their molecular weight, galacturonic acid content, and chemical modifications. Additionally, CPs have excellent bioavailability, biocompatibility, and biodegradability, which make them promising candidates for applications in the food, medicine, and cosmetic industries. The article also scrutinized the potential development and future research directions of CPs. Overall, this article provides comprehensive knowledge and underpinnings of CPs for future research and development as therapeutic agents and multifunctional food additives.

Hippo Kinase MST1-Mediated Cell Metabolism Reprograms the Homeostasis and Differentiation of Granulocyte Progenitor Cells.

The mechanism of the development of granulocyte progenitor cells into neutrophils under steady-state and pathological conditions remains unclear. In this study, our results showed that with the development of neutrophils from hematopoietic stem cells to mature neutrophils, the expression level of the Hippo kinase MST1 gradually increased. Mst1-specific deficiency in myeloid cells caused neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte-macrophage progenitors under steady-state conditions and during Listeria monocytogenes infection. Mechanistically, mTOR and HIF1α signaling are required for regulating the balance between glycolysis and succinate dehydrogenase-mediated oxidative phosphorylation, which is crucial for Mst1-/--induced proliferation of granulocyte-monocyte progenitors, lineage-decision factor C/EBPα expression, and granulopoiesis. HIF1α directly regulated C/EBPα promoter activities. Blocking mTOR and HIF1α or adjusting the balance between glycolysis and succinate dehydrogenase-mediated oxidative phosphorylation reversed the granulopoiesis induced by Mst1-/- under steady-state conditions or infection in mice. Thus, our findings identify a previously unrecognized interplay between Hippo kinase MST1 signaling and mTOR-HIF1α metabolic reprogramming in granulocyte progenitor cells that underlies granulopoiesis.

Aryl hydrocarbon receptor nuclear translocator limits the recruitment and function of regulatory neutrophils against colorectal cancer by regulating the gut microbiota.

BACKGROUND: Although the role and mechanism of neutrophils in tumors have been widely studied, the precise effects of aryl hydrocarbon receptor nuclear translocator (ARNT) on neutrophils remain unclear. In this study, we investigated the roles of ARNT in the function of CD11b+Gr1+ neutrophils in colitis-associated colorectal cancer. METHODS: Wild-type (WT), ARNT myeloid-specific deficient mice and a colitis-associated colorectal cancer mouse model were used in this study. The level and functions of CD11b+Gr1+ cells were evaluated by flow cytometry and confocal microscopy. RESULTS: We found that ARNT deficiency drives neutrophils recruitment, neutrophil extracellular trap (NET) development, inflammatory cytokine secretion and suppressive activities when cells enter the periphery from bone marrow upon colorectal tumorigenesis. ARNT deficiency displays similar effects to aryl hydrocarbon receptor (AHR) deficiency in neutrophils. CXCR2 is required for NET development, cytokine production and recruitment of neutrophils but not the suppressive activities induced by Arnt-/- in colorectal cancer. The gut microbiota is essential for functional alterations in Arnt-/- neutrophils to promote colorectal cancer growth. The colorectal cancer effects of Arnt-/- neutrophils were significantly restored by mouse cohousing or antibiotic treatment. Intragastric administration of the feces of Arnt-/- mice phenocopied their colorectal cancer effects. CONCLUSION: Our results defined a new role for the transcription factor ARNT in regulating neutrophils recruitment and function and the gut microbiota with implications for the future combination of gut microbiota and immunotherapy approaches in colorectal cancer.

The hippo kinase MST1 negatively regulates the differentiation of follicular helper T cells.

Follicular helper T (TFH ) cells are essential for inducing germinal centre (GC) reactions to mediate humoral adaptive immunity and antiviral effects, but the mechanisms of TFH cell differentiation remain unclear. Here, we found that the hippo kinase MST1 is critical for TFH cell differentiation, GC formation, and antibody production under steady-state conditions and viral infection. MST1 deficiency intrinsically enhanced TFH cell differentiation and GC reactions in vivo and in vitro. Mechanistically, mTOR and HIF1α signalling is involved in glucose metabolism and increased glycolysis and decreased OXPHOS, which are critically required for MST1 deficiency-directed TFH cell differentiation. Moreover, upregulated Foxo3 expression is critically responsible for TFH cell differentiation induced by Mst1-/- . Thus, our findings identify a previously unrecognized relationship between hippo kinase MST1 signalling and mTOR-HIF1α-metabolic reprogramming coupled with Foxo3 signalling in reprogramming TFH cell differentiation.

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis.

Growth differentiation factor 15 (GDF-15) has been suggested as a potential biomarker of preeclampsia. However, previous studies evaluating circulating GDF-15 in women with preeclampsia showed inconsistent results. A meta-analysis was performed accordingly in this study. Observational studies comparing circulating GDF-15 between women with preeclampsia normal pregnancy were identified by search of electronic databases including PubMed, Embase, Web of Science, Wanfang, and CNKI. The Newcastle-Ottawa Scale (NOS) was used for assessing the quality of the studies. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Eleven observational studies including 498 women with preeclampsia and 2349 women with normal pregnancy contributed to the meta-analysis. Results showed that compared to controls of women with normal pregnancy at least matched for gestational ages, women with preeclampsia had significantly higher circulating GDF-15 at the diagnosis [standard mean difference (SMD): 0.66, 95% confidence interval (CI): 0.16 to 1.17, p=0.01, I2=93%]. Subgroup analysis showed consistent results in women with preterm and term preeclampsia in Asian and non-Asian women and in studies with different quality scores, which were not statistically significant between subgroups (p for subgroup difference>0.05). Moreover, a higher level of GDF-15 was also found before the diagnosis in women who subsequently developed preeclampsia than those who did not (SMD: 1.32, 95% CI: 0.45 to 2.18, p=0.003, I2=89%). In conclusion, a higher circulating GDF-15 is observed in women with preeclampsia even before the diagnosis of the disease.

Modulation of tumor-associated macrophages in colitis-associated colorectal cancer.

Intestinal macrophages are the most abundant immune cells in the small and large intestine, which maintain intestinal homeostasis by clearing invading bacteria and dead cells, secreting anti-inflammatory cytokines, and inducing tolerance to symbiotic bacteria and food particles. In addition, as antigen-presenting cells, they also participate in eliciting adaptive immune responses through bridging innate immune responses. After the intestinal homeostasis is disrupted, the damaged or apoptotic intestinal epithelial cells cannot be effectively cleared, and the infection of exogenous pathogens and leakage of endogenous antigens lead to persistent intestinal inflammation. Long-term chronic inflammation is one of the important causes of colitis-associated carcinogenesis (CAC). Tumor microenvironment (TME) is gradually formed around tumor cells, in which tumor associated macrophage (TAMs) is not only the builder, but also regulated by TME. This review just briefly summarized the role of intestinal macrophages under physiological and pathological inflammatory and cancerous conditions, and current therapeutic strategies for intestinal diseases targeting macrophages.

Dendritic cell Piezo1 directs the differentiation of TH1 and Treg cells in cancer.

Dendritic cells (DCs) play an important role in anti-tumor immunity by inducing T cell differentiation. Herein, we found that the DC mechanical sensor Piezo1 stimulated by mechanical stiffness or inflammatory signals directs the reciprocal differentiation of TH1 and regulatory T (Treg) cells in cancer. Genetic deletion of Piezo1 in DCs inhibited the generation of TH1 cells while driving the development of Treg cells in promoting cancer growth in mice. Mechanistically, Piezo1-deficient DCs regulated the secretion of the polarizing cytokines TGFß1 and IL-12, leading to increased TGFßR2-p-Smad3 activity and decreased IL-12Rß2-p-STAT4 activity while inducing the reciprocal differentiation of Treg and TH1 cells. In addition, Piezo1 integrated the SIRT1-hypoxia-inducible factor-1 alpha (HIF1α)-dependent metabolic pathway and calcium-calcineurin-NFAT signaling pathway to orchestrate reciprocal TH1 and Treg lineage commitment through DC-derived IL-12 and TGFß1. Our studies provide critical insight for understanding the role of the DC-based mechanical regulation of immunopathology in directing T cell lineage commitment in tumor microenvironments.

Selenium metabolism and regulation of immune cells in immune-associated diseases.

Selenium, as one of the essential microelements, plays an irreplaceable role in metabolism regulation and cell survival. Selenium metabolism and regulation have great effects on physiological systems especially the immune system. Therefore, selenium is tightly related to various diseases like cancer. Although recent research works have revealed much about selenium metabolism, the ways in which selenium regulates immune cells' functions and immune-associated diseases still remain much unclear. In this review, we will briefly introduce the regulatory role of selenium metabolism in immune cells and immune-associated diseases.

Protein Tyrosine Phosphatase PTPRO Signaling Couples Metabolic States to Control the Development of Granulocyte Progenitor Cells.

Protein tyrosine phosphatase (PTPase) is critically involved in the regulation of hematopoietic stem cell development and differentiation. Roles of novel isolated receptor PTPase PTPRO from bone marrow hematopoietic stem cells in granulopoiesis have not been investigated. PTPRO expression is correlated with granulocytic differentiation, and Ptpro -/- mice developed neutrophilia, with an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors under steady-state and potentiated innate immune responses against Listeria monocytogenes infection. Mechanistically, mTOR and HIF1α signaling engaged glucose metabolism and initiated a transcriptional program involving the lineage decision factor C/EBPα, which is critically required for the PTPRO deficiency-directed granulopoiesis. Genetic ablation of mTOR or HIF1α or perturbation of glucose metabolism suppresses progenitor expansion, neutrophilia, and higher glycolytic activities by Ptpro -/- In addition, Ptpro -/- upregulated HIF1α regulates the lineage decision factor C/EBPα promoter activities. Thus, our findings identify a previously unrecognized interplay between receptor PTPase PTPRO signaling and mTOR-HIF1α metabolic reprogramming in progenitor cells of granulocytes that underlies granulopoiesis.

Immunoregulatory Role of the Mechanosensitive Ion Channel Piezo1 in Inflammation and Cancer.

Piezo1 was originally identified as a mechanically activated, nonselective cation ion channel, with significant permeability to calcium ions, is evolutionally conserved, and is involved in the proliferation and development of various types of cells, in the context of various types of mechanical or innate stimuli. Recently, our study and work by others have reported that Piezo1 from all kinds of immune cells is involved in regulating many diseases, including infectious inflammation and cancer. This review summarizes the recent progress made in understanding the immunoregulatory role and mechanisms of the mechanical receptor Piezo1 in inflammation and cancer and provides new insight into the biological significance of Piezo1 in regulating immunity and tumors.

[Exploring and practicing over 80 years in traditional Chinese medicine: the academic career of professor XUE Chong-cheng].

This paper reviewes the clinical and scientific research history of professor XUE Chong-cheng and summarizes his academic thoughts and main achievements. Professor XUE Chong -cheng created the first personality and constitution inventory in China to lay the foundation for the discipline of TCM psychology; discovered meridian sensory conduction in phantom limbs and proposed the extension of the central model; invented a method for treating mental illness with a low-dose electroacupuncture convulsion therapy instrument; and interpreted the TCM medical model as a Time-Space-Social- Psychological-Biological medical model.

The direct and indirect regulation of follicular T helper cell differentiation in inflammation and cancer.

Follicular T helper (Tfh) cells play important roles in facilitating B-cell differentiation and inducing the antibody response in humoral immunity and immune-associated inflammatory diseases, including infections, autoimmune diseases, and cancers. However, Tfh cell differentiation is mainly achieved through self-directed differentiation regulation and the indirect regulation mechanism of antigen-presenting cells (APCs). During the direct intrinsic differentiation of naïve CD4+ T cells into Tfh cells, Bcl-6, as the characteristic transcription factor, plays the core role of transcriptional regulation. APCs indirectly drive Tfh cell differentiation mainly by changing cytokine secretion mechanisms. Altered metabolic signaling is also critically involved in Tfh cell differentiation. This review summarizes the recent progress in understanding the direct and indirect regulatory signals and metabolic mechanisms of Tfh cell differentiation and function in immune-associated diseases.

The crosstalk between gut bacteria and host immunity in intestinal inflammation.

The gut of mammals is considered as a harmonious ecosystem mediated by intestinal microbiota and the host. Both bacteria and mammalian immune cells show region-related distribution characteristics, and the interaction between the two could be demonstrated by synergetic roles in maintaining intestinal homeostasis and dysregulation in intestinal inflammation. The harmonious interplay between bacteria and host requires fine-tuned regulations by environmental and genetic factors. Thus, the disturbed immune response to microbial components or metabolites and dysbiosis related to immunodeficiency are absolute risk factors to intestinal inflammation and cancer. In this review, we discuss the crosstalk between bacteria and host immunity in the gut and highlight the critical roles of bidirectional regulation between bacteria and the mammalian immune system involved in intestinal inflammation.

Functional differentiation and regulation of follicular T helper cells in inflammation and autoimmunity.

Follicular T helper (TFH ) cells are specialized T cells that support B cells, which are essential for humoral immunity. TFH cells express the transcription factor B-cell lymphoma 6 (Bcl-6), chemokine (C-X-C motif) receptor (CXCR) 5, the surface receptors programmed cell death protein 1 (PD-1) and inducible T-cell costimulator (ICOS), the cytokine IL-21 and other molecules. The activation, proliferation and differentiation of TFH cells are closely related to dynamic changes in cellular metabolism. In this review, we summarize the progress made in understanding the development and functional differentiation of TFH cells. Specifically, we focus on the regulatory mechanisms of TFH cell functional differentiation, including regulatory signalling pathways and the metabolic regulatory mechanisms of TFH cells. In addition, TFH cells are closely related to immune-associated diseases, including infections, autoimmune diseases and cancers.

Targeting Myeloid-Derived Suppressor Cells in Cancer Immunotherapy.

Myeloid-derived suppressor cells (MDSCs), which are activated under pathological conditions, are a group of heterogeneous immature myeloid cells. MDSCs have potent capacities to support tumor growth via inhibition of the antitumoral immune response and/or the induction of immunosuppressive cells. In addition, multiple studies have demonstrated that MDSCs provide potential therapeutic targets for the elimination of immunosuppressive functions and the inhibition of tumor growth. The combination of targeting MDSCs and other therapeutic approaches has also demonstrated powerful antitumor effects. In this review, we summarize the characteristics of MDSCs in the tumor microenvironment (TME) and current strategies of cancer treatment by targeting MDSCs.

Regulations of Glycolytic Activities on Macrophages Functions in Tumor and Infectious Inflammation.

Macrophages differentiated into a classically activated (M1) or alternatively activated phenotype (M2) in infection and tumor, but the precise effects of glycolysis and oxidative phosphorylation (OXPHOS) metabolic pathway remain unclear. Herein, the effects of glycolysis or OXPHOS on macrophage polarizations were investigated using a pharmacological approach in mice. 2-Deoxy-D-glucose (2-DG) treatments, which blocks the key enzyme hexokinase of glycolysis, efficiently inhibits a specific switch to M1 lineage, decreasing the secretion of pro-inflammatory cytokines and expressions of co-stimulatory molecules associated with relieving infectious inflammation in vitro and in vivo. Glycolytic activation through the hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against infection. Dimethyl malonate (DMM) treatment, which blocks the key element succinate of OXPHOS, efficiently inhibits a specific switch to M2 lineage when macrophages receiving M2 stimulation, decreasing the secretion of anti-inflammatory cytokine and CD206 expressions. Mitochondrial dynamic alterations including mitochondrial mass, mitochondrial membrane potential (Dym) and ROS productions were critically for differentiation to the M2 phenotype, which conferred protection against anti-tumor immunity. Glycolysis is also required for macrophage M2 differentiation. Thus, these data provide a basis for a comprehensively understanding the role of glycolysis and OXPHOS in macrophage differentiation during anti-infection and anti-tumor inflammation.

Non-destructive estimation of field maize biomass using terrestrial lidar: an evaluation from plot level to individual leaf level.

BACKGROUND: Precision agriculture is an emerging research field that relies on monitoring and managing field variability in phenotypic traits. An important phenotypic trait is biomass, a comprehensive indicator that can reflect crop yields. However, non-destructive biomass estimation at fine levels is unknown and challenging due to the lack of accurate and high-throughput phenotypic data and algorithms. RESULTS: In this study, we evaluated the capability of terrestrial light detection and ranging (lidar) data in estimating field maize biomass at the plot, individual plant, leaf group, and individual organ (i.e., individual leaf or stem) levels. The terrestrial lidar data of 59 maize plots with more than 1000 maize plants were collected and used to calculate phenotypes through a deep learning-based pipeline, which were then used to predict maize biomass through simple regression (SR), stepwise multiple regression (SMR), artificial neural network (ANN), and random forest (RF). The results showed that terrestrial lidar data were useful for estimating maize biomass at all levels (at each level, R2 was greater than 0.80), and biomass estimation at leaf group level was the most precise (R2 = 0.97, RMSE = 2.22 g) among all four levels. All four regression techniques performed similarly at all levels. However, considering the transferability and interpretability of the model itself, SR is the suggested method for estimating maize biomass from terrestrial lidar-derived phenotypes. Moreover, height-related variables showed to be the most important and robust variables for predicting maize biomass from terrestrial lidar at all levels, and some two-dimensional variables (e.g., leaf area) and three-dimensional variables (e.g., volume) showed great potential as well. CONCLUSION: We believe that this study is a unique effort on evaluating the capability of terrestrial lidar on estimating maize biomass at difference levels, and can provide a useful resource for the selection of the phenotypes and models required to estimate maize biomass in precision agriculture practices.

Glucocorticoids Promote the Onset of Acute Experimental Colitis and Cancer by Upregulating mTOR Signaling in Intestinal Epithelial Cells.

The therapeutic effects of glucocorticoids on colitis and colitis-associated cancer are unclear. In this study, we investigated the therapeutic roles of glucocorticoids in acute experimental ulcerative colitis and colitis-associated cancer in mice and their immunoregulatory mechanisms. Murine acute ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with dexamethasone (Dex) at different doses. Dex significantly exacerbated the onset and severity of DSS-induced colitis and potentiated mucosal inflammatory macrophage and neutrophil infiltration, as well as cytokine production. Furthermore, under inflammatory conditions, the expression of the glucocorticoid receptor (GR) did not change significantly, while mammalian target of rapamycin (mTOR) signaling was higher in colonic epithelial cells than in colonic immune cells. The deletion of mTOR in intestinal epithelial cells, but not that in myeloid immune cells, in mice significantly ameliorated the severe course of colitis caused by Dex, including weight loss, clinical score, colon length, pathological damage, inflammatory cell infiltration and pro-inflammatory cytokine production. These data suggest that mTOR signaling in intestinal epithelial cells, mainly mTORC1, plays a critical role in the Dex-induced exacerbation of acute colitis and colitis-associated cancer. Thus, these pieces of evidence indicate that glucocorticoid-induced mTOR signaling in epithelial cells is required in the early stages of acute ulcerative colitis by modulating the dynamics of innate immune cell recruitment and activation.