-
Birth Defects Research Aug 2023During the early phases of embryonic development, the yolk sac serves as an initial placenta in many animal species. While in some, this role subsides around the end of... (Review)
Review
During the early phases of embryonic development, the yolk sac serves as an initial placenta in many animal species. While in some, this role subsides around the end of active organogenesis, it continues to have important functions in rodents, alongside the chorio-allantoic placenta. The yolk sac is the initial site of hematopoiesis in many animal species including primates. Cells of epiblastic origin form blood islands that are the forerunners of hematopoietic cells and of the primitive endothelial cells that form the vitelline circulation. The yolk sac is also a major route of embryonic and fetal nutrition apparently as long as it functions. In mammals and especially rodents, macro and micronutrients are absorbed by active pinocytosis into the visceral yolk sac, degraded and the degradation products (i.e., amino acids) are then transferred to the embryo. Interference with the yolk sac function may directly reflect on embryonic growth and development, inducing congenital malformations or in extreme damage, causing embryonic and fetal death. In rodents, many agents were found to damage the yolk sac (i.e., anti-yolk sac antibodies or toxic substances interfering with yolk sac pinocytosis) subsequently affecting the embryo/fetus. Often, the damage to the yolk sac is transient while embryonic damage persists. In humans, decreased yolk sac diameter was associated with diabetic pregnancies and increased diameter was associated with pregnancy loss. In addition, culture of rat yolk sacs in serum obtained from pregnant diabetic women or from women with autoimmune diseases induced severe damage to the visceral yolk sac epithelium and embryonic malformations. It can be concluded that as a result of the crucial role of the yolk sac in the well-being of the early embryo, any damage to its normal function may severely and irreversibly affect further development of the embryo/fetus.
Topics: Pregnancy; Rats; Female; Humans; Animals; Rodentia; Endothelial Cells; Yolk Sac; Mammals; Pinocytosis
PubMed: 36949669
DOI: 10.1002/bdr2.2172 -
Frontiers in Cardiovascular Medicine 2023Endocytosis constitutes a cellular process in which cells selectively encapsulate surface substances into endocytic vesicles, also known as endosomes, thereby modulating... (Review)
Review
Endocytosis constitutes a cellular process in which cells selectively encapsulate surface substances into endocytic vesicles, also known as endosomes, thereby modulating their interaction with the environment. Platelets, as pivotal hematologic elements, play a crucial role not only in regulating coagulation and thrombus formation but also in facilitating tumor invasion and metastasis. Functioning as critical components in the circulatory system, platelets can internalize various endosomal compartments, such as surface receptors, extracellular proteins, small molecules, and pathogens, from the extracellular environment through diverse endocytic pathways, including pinocytosis, phagocytosis, and receptor-mediated endocytosis. We summarize recent advancements in platelet endocytosis, encompassing the catalog of cargoes, regulatory mechanisms, and internal trafficking routes. Furthermore, we describe the influence of endocytosis on platelet regulatory functions and related physiological and pathological processes, aiming to offer foundational insights for future research into platelet endocytosis.
PubMed: 38264257
DOI: 10.3389/fcvm.2023.1308170 -
TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.The Journal of Experimental Medicine Jul 2024Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug...
Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.
Topics: Animals; Neutrophils; STAT3 Transcription Factor; Mice; Lung Neoplasms; DNA-Binding Proteins; Chemokine CXCL5; Proto-Oncogene Proteins; Humans; Dioxygenases; Pinocytosis; Cell Line, Tumor; Neutrophil Infiltration; Mice, Knockout; Mice, Inbred C57BL; Lipid Metabolism
PubMed: 38805014
DOI: 10.1084/jem.20240111 -
Journal of Extracellular Vesicles Apr 2024Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug-delivery vehicles. However, clinical...
Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug-delivery vehicles. However, clinical drugs modulating EV levels are still lacking. Here, we show that proton pump inhibitors (PPIs) reduce EVs by enhancing macropinocytosis-mediated EV uptake. PPIs accelerate intestinal cell endocytosis of autocrine immunosuppressive EVs through macropinocytosis, thereby aggravating inflammatory bowel disease. PPI-induced macropinocytosis facilitates the clearance of immunosuppressive EVs from tumour cells, improving antitumor immunity. PPI-induced macropinocytosis also increases doxorubicin and antisense oligonucleotides of microRNA-155 delivery efficiency by EVs, leading to enhanced therapeutic effects of drug-loaded EVs on tumours and acute liver failure. Mechanistically, PPIs reduce cytosolic pH, promote ATP6V1A (v-ATPase subunit) disassembly from the vacuolar membrane and enhance the assembly of plasma membrane v-ATPases, thereby inducing macropinocytosis. Altogether, our results reveal a mechanism for macropinocytic regulation and PPIs as potential modulators of EV levels, thus regulating their functions.
Topics: Proton Pump Inhibitors; Extracellular Vesicles; Endocytosis; Pinocytosis; Adenosine Triphosphatases
PubMed: 38532609
DOI: 10.1002/jev2.12426 -
Biochemical and Biophysical Research... Oct 2023Extracellular substances, including membrane-impermeable nutrients, are taken up by cells via endocytosis. Endocytosis is also an important pathway for antigen uptake by...
Extracellular substances, including membrane-impermeable nutrients, are taken up by cells via endocytosis. Endocytosis is also an important pathway for antigen uptake by antigen-presenting cells such as monocytes, macrophages, dendritic cells, and B cells. In this study, we investigated the regulatory mechanism of endocytosis in THP-1 cells, a monocytic leukemia cell line. We analyzed the effect of IgG and insulin, which are abundant in the serum and play important roles in immunity and metabolism, respectively, on the endocytic activity in THP-1 cells. The results indicated that IgG and insulin enhance pinocytosis and phagocytosis via activation of phosphatidylinositol 3-kinase (PI3K). Our results suggest that IgG and insulin contribute to the maintenance of endocytic activity and are important for antigen presentation and nutrient uptake.
Topics: Humans; Phosphatidylinositol 3-Kinases; Phosphatidylinositol 3-Kinase; Insulin; THP-1 Cells; Endocytosis; Monocytes; Immunoglobulin G
PubMed: 37696069
DOI: 10.1016/j.bbrc.2023.09.008 -
Journal of Neuroscience Methods Sep 2023Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging...
BACKGROUND
Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods.
METHODS
This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test.
RESULTS
The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment.
CONCLUSIONS
HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies.
AVAILABILITY OF DATA AND MATERIALS
The datasets supporting the conclusions of this article are included within the article and its supplementary materials.
Topics: Humans; Glioblastoma; Pinocytosis; Cell Line; Cell Proliferation; Tumor Microenvironment
PubMed: 37574078
DOI: 10.1016/j.jneumeth.2023.109947 -
International Journal of Biological... Nov 2023The flower of Hylocereus undatus (Haw.) Britton et Rose is widely recognized as a kind of medicine-food homologous resource due to its high nutritional value. However,...
The flower of Hylocereus undatus (Haw.) Britton et Rose is widely recognized as a kind of medicine-food homologous resource due to its high nutritional value. However, there is a lack of in-depth studies on the purification, structure, antioxidative and immunoregulatory activities of polysaccharides from H. undatus flowers (FHRP). The objective of this study was to investigate the primary structure, antioxidative and immunoregulatory activities of the polysaccharides extracted from Hylocereus undatus flower using water extraction and chromatogram purification. Three polysaccharide fractions named FHRP-1, FHRP-2 and FHRP-3 were obtained. The results showed that FHRP-1, FHRP-2 and FHRP-3 (200-800 μg/mL) treatment for 24 h significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and reduced the malondialdehyde (MDA) production in RAW 246.7 cells under HO-induced oxidative stress. Additionally, all three fractions exhibited immunoregulatory activities by enhancing the pinocytosis of RAW 264.7 cells and promoting the production of nitric oxide (NO), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Among three polysaccharide fractions, FHRP-3 exhibited the most promising antioxidative and immunoregulatory properties, which was attributed to its higher content of uronic acid, moderate molecular weight, and triple-helix conformation. These findings provide preliminary insights into the primary structural information and biological activities of FHRP.
Topics: Animals; Antioxidants; Polysaccharides; Mice; Flowers; RAW 264.7 Cells; Cactaceae; Nitric Oxide; Oxidative Stress; Superoxide Dismutase; Hydrogen Peroxide; Immunologic Factors; Malondialdehyde; Catalase
PubMed: 37598818
DOI: 10.1016/j.ijbiomac.2023.126408 -
Plants (Basel, Switzerland) Dec 2023M.Bieb is a promising repository of active phytochemicals. These bioactive compounds work synergistically to promote the plant's antioxidant, anticancer, and...
M.Bieb is a promising repository of active phytochemicals. These bioactive compounds work synergistically to promote the plant's antioxidant, anticancer, and immunomodulatory capabilities. The present study aimed to discover the potential immunomodulatory and cytotoxicity of different extracts of roots. Aqueous ethanol (70%), aqueous methanol (90%), ethyl acetate, and n-hexane extracts were tested against five cell lines (T47D, MDA-MB231, Caco-2, EMT6/P, and Vero). Among these extracts, ethyl acetate and n-hexane extracts showed significant activity in inhibiting the proliferation of cancerous cells because of the presence of several phytochemical compounds, including flavonoids, phenolics, and alkaloids. The n-hexane extract was the most potent extract against T47D and Caco-2 cell lines and had IC values of 0.067 mg/mL and 0.067 mg/mL, respectively. In comparison, ethyl acetate extract was active against T47D and MDAMB231, and IC values were 0.0179 mg/mL and 0.03 mg/mL, respectively. Both n-hexane and ethyl acetate extracts reduced tumor size (by 49.981% and 51.028%, respectively). Remarkably, extracts decreased the average weight of the tumor cells in the in vivo model. The plant induced significant apoptotic activity by the activation of caspase-3, immunomodulation of macrophages, and triggering of pinocytosis. The implications of these intriguing findings demand additional research to broaden the scope of the understanding of this field, opening the doors to the possibilities of using M.Bieb as an effective cancer treatment adjuvant in the future.
PubMed: 38202350
DOI: 10.3390/plants13010042 -
Advanced Healthcare Materials Oct 2023Bioactive macromolecules show great promise for the treatment of various diseases. However, the cytosolic delivery of peptide-based drugs remains a challenging task...
Bioactive macromolecules show great promise for the treatment of various diseases. However, the cytosolic delivery of peptide-based drugs remains a challenging task owing to the existence of multiple intracellular barriers and ineffective endosomal escape. To address these issues, herein, programmable self-assembling peptide vectors are reported to amplify cargo internalization into the cytoplasm through receptor-activated macropinocytosis. Programmable self-assembling peptide vector-active human epidermal growth factor receptor-2 (HER2) signaling induces the receptor-activated macropinocytosis pathway, achieving efficient uptake in tumor cells. Shrinking macropinosomes accelerate the process of assembly dynamics and form nanostructures in the cytoplasm to increase peptide-based cargo accumulation and retention. Inductively coupled plasma mass (ICP-MS) spectrometry quantitative analysis indicates that the Gd delivery efficiency in tumor tissue through the macropinocytosis pathway is improved 2.5-fold compared with that through the use of active targeting molecular delivery. Finally, compared with nanoparticles and active targeting delivery, the delivery of bioactive peptide drugs through the self-assembly of peptide vectors maintains high drug activity (the IC decreased twofold) in the cytoplasm and achieves effective inhibition of tumor cell growth. Programmable self-assembling peptide vectors represent a promising platform for the intracellular delivery of diverse bioactive drugs, including molecular drugs, peptides, and biologics.
Topics: Humans; Peptides; Pinocytosis; Cytosol; Endosomes; Nanostructures; Carrier Proteins
PubMed: 37449948
DOI: 10.1002/adhm.202301162 -
Frontiers in Immunology 2024Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality but lacks specific therapeutic options. Diverse endocytic processes play a key... (Review)
Review
Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality but lacks specific therapeutic options. Diverse endocytic processes play a key role in all phases of acute lung injury (ALI), including the initial insult, development of respiratory failure due to alveolar flooding, as a consequence of altered alveolar-capillary barrier function, as well as in the resolution or deleterious remodeling after injury. In particular, clathrin-, caveolae-, endophilin- and glycosylphosphatidyl inositol-anchored protein-mediated endocytosis, as well as, macropinocytosis and phagocytosis have been implicated in the setting of acute lung damage. This manuscript reviews our current understanding of these endocytic pathways and subsequent intracellular trafficking in various phases of ALI, and also aims to identify potential therapeutic targets for patients with ARDS.
Topics: Humans; Respiratory Distress Syndrome; Endocytosis; Acute Lung Injury; Pinocytosis; Phagocytosis
PubMed: 38533500
DOI: 10.3389/fimmu.2024.1360370