Biological characteristics of mechanosensitive channels MscS and MscL in Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is an important respiratory pathogen that can cause porcine contagious pleuropneumonia (PCP), resulting in significant economic losses in swine industry. Microorganisms are subjected to drastic changes in environmental osmolarity. In order to alleviate the drastic rise or fall of osmolarity, cells activate mechanosensitive channels MscL and MscS through tension changes. MscL not only regulates osmotic pressure but also has been reported to secrete protein and uptake aminoglycoside antibiotic. However, MscL and MscS, as the most common mechanosensitive channels, have not been characterized in A. pleuropneumoniae. In this study, the osmotic shock assay showed that MscL increased sodium adaptation by regulating cell length. The results of MIC showed that deletion of mscL decreased the sensitivity of A. pleuropneumoniae to multiple antibiotics, while deletion of mscS rendered A. pleuropneumoniae hypersensitive to penicillin. Biofilm assay demonstrated that MscL contributed the biofilm formation but MscS did not. The results of animal assay showed that MscL and MscS did not affect virulence in vivo. In conclusion, MscL is essential for sodium hyperosmotic tolerance, biofilm formation, and resistance to chloramphenicol, erythromycin, penicillin, and oxacillin. On the other hand, MscS is only involved in oxacillin resistance.IMPORTANCEBacterial resistance to the external environment is a critical function that ensures the normal growth of bacteria. MscL and MscS play crucial roles in responding to changes in both external and internal environments. However, the function of MscL and MscS in Actinobacillus pleuropneumoniae has not yet been reported. Our study shows that MscL plays a significant role in osmotic adaptation, antibiotic resistance, and biofilm formation of A. pleuropneumoniae, while MscS only plays a role in antibiotic resistance. Our findings provide new insights into the functional characteristics of MscL and MscS in A. pleuropneumoniae. MscL and MscS play a role in antibiotic resistance and contribute to the development of antibiotics for A. pleuropneumoniae.

Design and Analysis of a Textured Cu-Encapsulated Ni Tube for Low-Reflection Electromagnetic Interference Shielding Material.

With the frequent increase and update of electromagnetic interference (EMI) shielding materials, a low-resolution material that can absorb most electromagnetic waves, thereby effectively reducing the secondary pollution, is urgently needed. However, the excellent performance, flexibility, and low cost of these methods are usually incompatible with current reports. To address the above dilemma, we reported a facile solution for fabricating a low-reflection and high-performance EMI shielding composite by means of electroless nickel plating (EP-Ni), electroless copper plating (EP-Cu), annealing, and coating with a polydimethylsiloxane (PDMS) polymer with the structure of a Ni@Cu tube encapsulated with PDMS. The results indicate that the active groups on vegetable wool can act as active sites for the absorption of the Pd catalyst, thereby catalyzing the reduction of Ni2+, Cu2+, and the subsequent deposition on the plant fiber surface. Notably, the Ni@Cu-encapsulated plant fibers decreased during annealing at 100 °C. According to the segregated network and synergistic effect of the porous structure, the as-fabricated EMI shielding material demonstrated high absorption and low reflection, in which the power coefficient of the T value was approximately 0.0001, the R value was about 0.1764 (a decrease of 27.5% compared that of EP-Ni cotton), and the A value was approximately 0.8235.

S100A4-dependent glycolysis promotes lymphatic vessel sprouting in tumor.

Tumor-induced lymphangiogenesis promotes the formation of new lymphatic vessels, contributing to lymph nodes (LNs) metastasis of tumor cells in both mice and humans. Vessel sprouting appears to be a critical step in this process. However, how lymphatic vessels sprout during tumor lymphangiogenesis is not well-established. Here, we report that S100A4 expressed in lymphatic endothelial cells (LECs) promotes lymphatic vessel sprouting in a growing tumor by regulating glycolysis. In mice, the loss of S100A4 in a whole body (S100A4-/-), or specifically in LECs (S100A4ΔLYVE1) leads to impaired tumor lymphangiogenesis and disrupted metastasis of tumor cells to sentinel LNs. Using a 3D spheroid sprouting assay, we found that S100A4 in LECs was required for the lymphatic vessel sprouting. Further investigations revealed that S100A4 was essential for the position and motility of tip cells, where it activated AMPK-dependent glycolysis during lymphatic sprouting. In addition, the expression of S100A4 in LECs was upregulated under hypoxic conditions. These results suggest that S100A4 is a novel regulator of tumor-induced lymphangiogenesis. Targeting S100A4 in LECs may be a potential therapeutic strategy for lymphatic tumor metastasis.

Fabrication of Ni-Encapsulated Carbon Tube/Poly(dimethylsiloxane) Composite Materials for Lightweight and Flexible Electromagnetic Interference Shielding Material.

The exploration of flexible and lightweight electromagnetic interference (EMI) shielding materials with excellent shielding effectiveness, as a means to effectively alleviate electromagnetic pollution, is still a tremendous challenge. This paper proposes a conducting material named the textured Ni-encapsulated carbon tube, which can be applied in EMI shielding material by being inserted in the center of a poly(dimethysiloxane) (PDMS) polymer. We demonstrated that Pd2+ could be absorbed by the active groups on the plant fiber surface to catalyze the reduction of Ni2+ as a catalytic center by means of a textured Ni-encapsulated plant fiber. Owing to the outstanding heat-conducting capability of the Ni coating, the inner plant fiber was carbonized and attached to the Ni-tube inside the surface during annealing. To be precise, the textured Ni-encapsulated C tube was fabricated successfully after annealing at 300 °C. On further increasing the annealing temperature, the C tube disappeared gradually with the Ni coating being oxidized to NiO. Of note, the C tube acted as a support layer for the external Ni coating, providing sufficient mechanical strength. When combined with the coating PDMS layer, a flexible and lightweight EMI shielding material is fabricated successfully. It displays an outstanding EMI shielding effectiveness of 31.34 dB and a higher specific shielding efficiency of 27.5 dB·cm3/g, especially showing excellent mechanical property and flexibility with only 2 mm thickness. This study provides a new method to fabricate outstanding EMI shielding materials.

Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson's Disease Effect.

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 µM, while compounds 2 and 4 (100 µM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.

Tumor-derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1+ fibroblast and CCR8+ Treg cell interactions.

BACKGROUND: Since the lung is one of the most common sites for cancer metastasis, it could provide a suitable microenvironment for pre-metastatic niche (PMN) formation to facilitate tumor cell colonization. Regulatory T cells (Tregs) are an immunosuppressive cell type found ubiquitously in tumors and may play a crucial role in PNM formation. In this study, we investigated tumor-derived exosome (TDE)-induced Treg differentiation in the lung PMN as well as the underlying mechanisms. METHODS: TDEs were isolated from the Lewis lung carcinoma cell line (LLC-exo) and their effects on mouse pulmonary fibroblasts was investigated in vitro as well as on lung tumor formation and metastasis in a pre-injected mouse model. Immune cell populations in the lung were analyzed by flow cytometry. Expression of CCL1 and CCR8 was evaluated by immunofluorescence staining, qRT-PCR and Western blot analyses. Cytokine expression was measured using mouse cytokine arrays and ELISA. RESULTS: The number of CD4+ FoxP3+ Tregs was significantly increased in lungs in a LLC-exo pre-injected mouse model. Lung fibroblasts secreted increased amounts of CCL1 after co-culture with LLC-exo, which induced Treg differentiation by activating its specific receptor CCR8, ultimately contributing to the establishment of an immunologically tolerant PMN. Moreover, inhibiting the release of LLC-exo by GW4869, or blocking the CCL1-CCR8 axis using AZ084, suppressed Tregs differentiation and tumor metastasis in the lung. CONCLUSIONS: Collectively, our study provides a novel mechanism by which Tregs are activated to form an immunologically tolerant PMN and demonstrates a critical link among lung fibroblasts, Tregs and metastatic tumor cells.

Tie2-expressing monocytes as a novel angiogenesis-related cellular biomarker for non-small cell lung cancer.

To investigate the clinical value of Tie2-expressing monocytes (TEMs) in the early diagnosis of lung cancer and assess its correlation with angiogenesis, a total of 184 patients with non-small cell lung cancer (NSCLC), 101 patients with benign pulmonary disease (BPD), and 77 healthy controls were enrolled in our study. The distribution of TEMs in lung tissue was determined by immunofluorescence staining. Lung microvascular density was assessed by immunohistochemical staining. Receiver-operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of TEM frequency. Patients with NSCLC were followed up for 26 months. We found that the TEM frequency in peripheral blood monocytes of patients with NSCLC was significantly greater than that in patients with BPD and healthy controls. TEM frequency showed a correlation with NSCLC recurrence. The majority of TEMs in tumor tissues were localized around blood vessels; tumoral TEM frequency showed a positive correlation with microvascular density. High percentage of TEMs in the peripheral blood was associated with poor overall survival. ROC curve analysis revealed the potential diagnostic value of circulating TEM frequency in NSCLC. Thus, we believe that TEM frequency is related to angiogenesis in tumor tissues and may serve as a diagnostic marker for NSCLC.

Tumour-derived exosomal miR-3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor-κB of local fibroblasts.

Tumour-derived exosomes have been shown to induce pre-metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC-derived exosomes were mainly engulfed by lung fibroblasts and led to the NF-κB signalling activation. Further studies indicated that the exosomal miR-3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR-3473b could reverse the exosome-mediated NF-κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR-3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.

ECRG4 as a novel tumor suppressor gene inhibits colorectal cancer cell growth in vitro and in vivo.

Esophageal cancer related gene 4 (ECRG4) as a tumor suppressor gene inhibits the growth and development of various tumors. Colorectal cancer (CRC), a common malignant tumor in the digestive tract worldwide, is a leading cause of death. The aim of our study was to assess the tumor-suppressing effect of ECRG4 on CRC and explore its related mechanisms in vitro and in vivo. The expression levels of ECRG4 were measured in colorectal cancer tissues and para-carcinoma tissues. ECRG4 gene was transfected into CRC cells to investigate its effect on cell proliferation by MTT, colony formation assay, and cell cycle analysis. Cell apoptosis was assessed by annexin-V/PI, Hoechst 33342 staining, and analysis of apoptosis-related protein expressions in vitro. The in vivo tumorigenesis assays were performed in nude mice. According to the results, there was a lower expression of ECRG4 in CRC tissues compared with normal tissues, which was strongly associated with histology differentiation and lymph node metastasis. Additionally, overexpression of ECRG4 had a significant inhibitory effect on proliferation and promoted apoptosis in Caco-2 and SW480 cells. Moreover, we found that the overexpression of ECRG4 inhibited tumorigenesis in vivo by diminishing the volume and weight of the tumors and inducing apoptosis of tumor cells. Our study indicates that ECRG4 may be a new potential target and prognostic factor for patients with CRC.

The role of amino acid metabolism in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an inflammatory chronic liver disease with persistent and recurrent immune-mediated liver injury. The exact cause of AIH is still not fully understood, but it is believed to be primarily due to an abnormal activation of the immune system, leading to autoimmune injury caused by the breakdown of autoimmune tolerance. Although the pathogenesis of AIH remains unclear, recent studies have shown that abnormalities in amino acid metabolism play significant roles in its development. These abnormalities in amino acid metabolism can lead to remodeling of metabolic processes, activation of signaling pathways, and immune responses, which may present new opportunities for clinical intervention in AIH. In this paper, we first briefly outline the recent progress of clinically relevant research on AIH, focusing on the role of specific amino acid metabolism (including glutamine, cysteine, tryptophan, branched-chain amino acids, etc.) and their associated metabolites, as well as related pathways, in the development of AIH. Furthermore, we discuss the scientific issues that remain to be resolved regarding amino acid metabolism, AIH development and related clinical interventions, with the aim of contributing to the future development of amino acid metabolism-based as a new target for the clinical diagnosis and treatment of AIH.

Chemotherapy-induced PTEN-L secretion promotes the selection of PTEN-deficient tumor cells.

BACKGROUND: PTEN loss has been identified in various tumor types and is linked to unfavorable clinical outcomes. In addition to PTEN mutation, multiple mechanisms contribute to PTEN loss during tumor development. However, the natural selection process of PTEN-deficient tumor cells remains unclear. Here, we aimed at further elucidating the role of PTEN-L in tumor progression. METHODS: PTEN knockout cell lines were generated using CRISPR/Cas9 technology. Ni-NTA affinity column chromatography was employed for PTEN-L purification. Tumor cell metastasis was evaluated in murine models and observed using the IVIS Spectrum Imaging System. RNA-sequencing, western blotting, PCR, flow cytometry, and cell proliferation assays were employed to investigate tumor cell dormancy and related mechanisms. RESULTS: The chemotherapeutic drugs, cisplatin, paclitaxel, and doxorubicin, induced tumor cells to secrete PTEN-long (PTEN-L), which shields PTEN-deficient tumor cells from chemotherapy-induced apoptosis better than it shields PTEN-intact cells. Further investigation revealed that PTEN-L treatment induced dormancy in PTEN-null tumor cells, characterized by an increase in p16 and p27 levels, cell-cycle arrest, reduced cell proliferation, and enhanced DNA repair. Furthermore, PTEN-L treatment selectively promoted the accumulation and growth of PTEN-null tumor cells in the lungs of C57BL/6J mice, while evading immune surveillance. Mechanistically, PTEN-L induced dormancy in PTEN-null tumor cells by activating the p38 signaling pathway. Addition of a p38 inhibitor effectively reversed dormancy and growth of PTEN-deficient tumor cells in the lungs. We also demonstrated that PTEN expression played a pivotal role in determining the outcome of PTEN-L-mediated antitumor therapy. CONCLUSIONS: In summary, PTEN-L was identified as a potent inducer of dormancy in PTEN-deficient tumor cells, which increased their efficient selection within the tumor microenvironment.

IFN-γ-responsiveness of lymphatic endothelial cells inhibits melanoma lymphatic dissemination via AMPK-mediated metabolic control.

The integrity of the lymphatic system is critical for preventing the dissemination of tumor cells, such as melanoma, to distant parts of the body. IFN-γ is well studied as a negative regulator for lymphangiogenesis, which is strongly associated with cancer metastasis. However, the exact mechanisms underlying this process remain unclear. In the present study, we investigated whether IFN-γ signaling in lymphatic endothelial cells (LECs) affects tumor cell dissemination by regulating the barrier function of tumor-associated lymphatic vessels. Using LEC-specific IFN-γ receptor (IFN-γR) knockout mice, we found that the loss of IFN-γR in LECs increased the dissemination of melanoma cells into the draining lymph nodes. Notably, IFN-γ signaling in LECs inhibited trans-lymphatic endothelial cell migration of melanoma cells, indicating its regulation of lymphatic barrier function. Further investigations revealed that IFN-γ upregulated the expression of the tight junction protein Claudin-3 in LECs, while knockdown of Claudin-3 in LECs abolished IFN-γ-induced inhibition of trans-lymphatic endothelial migration activity. Mechanistically, IFN-γ inhibits AMPK signaling activation, which is involved in the regulation of fatty acid metabolism. Modulating fatty acid metabolism and AMPK activation in LECs also affected the lymphatic dissemination of melanoma cells, further confirming that this process is involved in IFN-γ-induced regulation of lymphatic barrier function. These results provide novel insights into how IFN-γ modulates tight junctions in LECs, inhibiting the dissemination of melanoma cells via the lymphatic vessels.

Targeting lipid metabolism of macrophages: A new strategy for tumor therapy.

BACKGROUND: Lipid metabolism has been implicated in a variety of normal cellular processes and strongly related to the development of multiple diseases, including tumor. Tumor-associated macrophage (TAM) has emerged as a crucial regulator in tumorigenesis and promising target for tumor treatment. AIM OF REVIEW: A thorough understanding of TAM lipid metabolism and its value in tumorigenesis may provide new ideas for TAM-based anti-tumor therapy. Key scientific concepts of review: TAMs can be divided into two main types, M1-like TAMs and M2-like TAMs, which play anti-tumor and pro-tumor functions in tumor occurrence and development, respectively. Accumulating evidence has shown that lipid metabolic reprogramming, including fatty acid uptake and utilization, cholesterol expulsion, controls the polarization of TAMs and affects the tumorgenesis. These advances in uncovering the intricacies of lipid metabolism and TAMs have yielded new insights on tumor development and treatment. In this review, we aim to provide an update on the current understanding of the lipid metabolic reprogramming made by TAMs to adapt to the harsh tumor microenvironment (TME). In particular, we emphasize that there is complex lipid metabolism connections between TAMs and distinct tumors, which influences TAM to bias from M1 to M2 phenotype in tumor progression, and ultimately promotes tumor occurrence and development. Finally, we discuss the existing issues on therapeutic strategies by reprogramming TAMs based on lipid metabolism regulation (or increasing the ratio of M1/M2-like TAMs) that could be applied in the future to clinical tumor treatment.

Hyperexpression of tumor necrosis factor receptor 2 inhibits differentiation of myeloid-derived suppressor cells by instigating apolarity during ageing.

During the ageing process, TNF-α can promote the expansion of myeloid-derived suppressor cells (MDSCs). However, it remains unclear which receptor(s) of TNF-α are involved in and how they modulate this process. Here, we report that TNFR2 hyperexpression induced by either TNF-α or IL-6, two proinflammatory factors of senescence-associated secretory phenotype (SASP), causes cellular apolarity and differentiation inhibition in aged MDSCs. Ex vivo overexpression of TNFR2 in young MDSCs inhibited their polarity and differentiation, whereas in vivo depletion of Tnfr2 in aged MDSCs promotes their differentiation. Consequently, the age-dependent increase of TNFR2 versus unaltered TNFR1 expression in aged MDSCs significantly shifts the balance of TNF-α signaling toward the TNFR2-JNK axis, which accounts for JNK-induced impairment of cell polarity and differentiation failure of aged MDSCs. Consistently, inhibiting JNK attenuates apolarity and partially restores the differentiation capacity of aged MDSCs, suggesting that upregulated TNFR2/JNK signaling is a key factor limiting MDSC differentiation during organismal ageing. Therefore, abnormal hyperexpression of TNFR2 represents a general mechanism by which extrinsic SASP signals disrupt intrinsic cell polarity behavior, thereby arresting mature differentiation of MDSCs with ageing, suggesting that TNFR2 could be a potential therapeutic target for intervention of ageing through rejuvenation of aged MDSCs.

A plant nonenveloped double-stranded RNA virus activates and co-opts BNIP3-mediated mitophagy to promote persistent infection in its insect vector.

Mitophagy that selectively eliminates damaged mitochondria is an essential mitochondrial quality control mechanism. Recently, mitophagy has been shown to be induced in host cells infected by a few animal viruses. Here, we report that southern rice black-streaked dwarf virus (SRBSDV), a plant nonenveloped double-stranded RNA virus, can also trigger mitophagy in its planthopper vector to prevent mitochondria-dependent apoptosis and promote persistent viral propagation. We find that the fibrillar structures constructed by the nonstructural protein P7-1 of SRBSDV directly target mitochondria via interaction with the mitophagy receptor BNIP3 (BCL2 interacting protein 3), and these mitochondria are then sequestered within autophagosomes to form mitophagosomes. Moreover, SRBSDV infection or P7-1 expression alone can promote BNIP3 dimerization on the mitochondria, and induce autophagy via the P7-1-ATG8 interaction. Furthermore, SRBSDV infection stimulates the phosphorylation of AMP-activated protein kinase (AMPK), resulting in BNIP3 phosphorylation via the AMPKα-BNIP3 interaction. Together, P7-1 induces BNIP3-mediated mitophagy by promoting the formation of phosphorylated BNIP3 dimers on the mitochondria. Silencing of ATG8, BNIP3, or AMPKα significantly reduces virus-induced mitophagy and viral propagation in insect vectors. These data suggest that in planthopper, SRBSDV-induced mitophagosomes are modified to accommodate virions and facilitate persistent viral propagation. In summary, our results demonstrate a previously unappreciated role of a viral protein in the induction of BNIP3-mediated mitophagy by bridging autophagosomes and mitochondria and reveal the functional importance of virus-induced mitophagy in maintaining persistent viral infection in insect vectors.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; CASP3: caspase 3; dsRNA: double strand RNA; ER: endoplasmic reticulum; FITC: fluorescein isothiocyanate; FKBP8: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GFP: green fluorescent protein; GST: glutathione S-transferase; padp: post-first access to diseased plants; Phos-tag: Phosphate-binding tag; PINK1: PTEN induced kinase 1; Sf9: Spodoptera frugiperda; SQSTM1: sequestosome 1; SRBSDV: southern rice black-streaked dwarf virus; STK11/LKB1: serine/threonine kinase 11; TOMM20: translocase of outer mitochondrial membrane 20; RBSDV: rice black-streaked dwarf virus; TUNEL: terminal deoxynucleotidyl dUTP nick end labeling; ULK1: unc-51 like autophagy activating kinase 1; VDAC1: voltage dependent anion channel 1.

A Comprehensive Review of Pea (Pisum sativum L.): Chemical Composition, Processing, Health Benefits, and Food Applications.

Pisum sativum L., commonly referred to as dry, green, or field pea, is one of the most common legumes that is popular and economically important. Due to its richness in a variety of nutritional and bioactive ingredients, the consumption of pea has been suggested to be associated with a wide range of health benefits, and there has been increasing focus on its potential as a functional food. However, there have been limited literature reviews concerning the bioactive compounds, health-promoting effects, and potential applications of pea up to now. This review, therefore, summarizes the literature from the last ten years regarding the chemical composition, physicochemical properties, processing, health benefits, and potential applications of pea. Whole peas are rich in macronutrients, including proteins, starches, dietary fiber, and non-starch polysaccharides. In addition, polyphenols, especially flavonoids and phenolic acids, are important bioactive ingredients that are mainly distributed in the pea coats. Anti-nutritional factors, such as phytic acid, lectin, and trypsin inhibitors, may hinder nutrient absorption. Whole pea seeds can be processed by different techniques such as drying, milling, soaking, and cooking to improve their functional properties. In addition, physicochemical and functional properties of pea starches and pea proteins can be improved by chemical, physical, enzymatic, and combined modification methods. Owing to the multiple bioactive ingredients in peas, the pea and its products exhibit various health benefits, such as antioxidant, anti-inflammatory, antimicrobial, anti-renal fibrosis, and regulation of metabolic syndrome effects. Peas have been processed into various products such as pea beverages, germinated pea products, pea flour-incorporated products, pea-based meat alternatives, and encapsulation and packing materials. Furthermore, recommendations are also provided on how to better utilize peas to promote their development as a sustainable and functional grain. Pea and its components can be further developed into more valuable and nutritious products.

Intestinal microbiota: A bridge between intermittent fasting and tumors.

Intestinal microbiota and their metabolites are essential for maintaining intestinal health, regulating inflammatory responses, and enhancing the body's immune function. An increasing number of studies have shown that the intestinal microbiota is tightly tied to tumorigenesis and intervention effects. Intermittent fasting (IF) is a method of cyclic dietary restriction that can improve energy metabolism, prolong lifespan, and reduce the progression of various diseases, including tumors. IF can affect the energy metabolism of tumor cells, inhibit tumor cell growth, improve the function of immune cells, and promote an anti-tumor immune response. Interestingly, recent research has further revealed that the intestinal microbiota can be impacted by IF, in particular by changes in microbial composition and metabolism. These findings suggest the complexity of the IF as a promising tumor intervention strategy, which merits further study to better understand and encourage the development of clinical tumor intervention strategies. In this review, we aimed to outline the characteristics of the intestinal microbiota and its mechanisms in different tumors. Of note, we summarized the impact of IF on intestinal microbiota and discussed its potential association with tumor suppressive effects. Finally, we proposed some key scientific issues that need to be addressed and envision relevant research prospects, which might provide a theoretical basis and be helpful for the application of IF and intestinal microbiota as new strategies for clinical interventions in the future.

Comparison of Soluble Dietary Fibers Extracted from Ten Traditional Legumes: Physicochemical Properties and Biological Functions.

Soluble dietary fibers (SDFs) exist as the major bioactive components in legumes, which exhibit various biological functions. To improve the potential applications of legume SDFs as healthy value-added products in the functional food industry, the physicochemical properties and biological functions of SDFs from ten selected traditional legumes, including mung bean, adzuki bean, red bean, red sword bean, black bean, red kidney bean, speckled kidney bean, common bean, white hyacinth bean, and pea, were studied and compared. Results showed that the physicochemical properties of SDFs varied in different species of legumes. All legume SDFs almost consisted of complex polysaccharides, which were rich in pectic-polysaccharides, e.g., homogalacturonan (HG) and rhamnogalacturonan I (RG I) domains. In addition, hemicelluloses, such as arabinoxylan, xyloglucan, and galactomannan, existed in almost all legume SDFs, and a large number of galactomannans existed in SDFs from black beans. Furthermore, all legume SDFs exhibited potential antioxidant, antiglycation, immunostimulatory, and prebiotic effects, and their biological functions differed relative to their chemical structures. The findings can help reveal the physicochemical and biological properties of different legume SDFs, which can also provide some insights into the further development of legume SDFs as functional food ingredients.

IFNγ blockade in capillary leak site improves tumour chemotherapy by inhibiting lactate-induced endocytosis of vascular endothelial-cadherins.

IFNγ has long been recognised as a key mediator of tumour immunity and angiostasis. However, IFNγ modulation for cancer therapy is still unsuccessful due to its complex effects on various host cells. In this study, we found that treatment of Lewis lung carcinoma transplants with cisplatin often caused IFNγ-dependent tumour vascular damage. IFNγ induced endothelial glycolysis and lactate production, leading to enhanced endocytosis of vascular endothelial (VE)-cadherin and vessel leakage. We have also developed anti-IFNγ nanoparticles coated with a clot-binding peptide CREKA (CREKA-lipo-anti-IFNγ), which targets the fibrin-fibronectin complex that appears in the leaky site of damaged tumour blood vessels. Blocking IFNγ activity in the leakage site of capillaries using nanoparticles rescued VE-cadherin distribution on the endothelial cellular surface, promoted blood vessel integrity, and improved drug delivery. In conclusion, IFNγ blockade in capillary leak site protected tumour blood vessels from lactate-dependent VE-cadherin loss and enhanced drug delivery during chemotherapy, which provides a basis for tissue-specific IFNγ blockade for tumour therapy.