Current topics in membranes最新文献

Malaria remains a major global threat, representing a severe public health problem worldwide. Annually, it is responsible for a high rate of morbidity and mortality in many tropical developing countries where the disease is endemic. The causative agent of malaria, Plasmodium spp., exhibits a complex life cycle, alternating between an invertebrate vector, which transmits the disease, and the vertebrate host. The disease pathology observed in the vertebrate host is attributed to the asexual development of Plasmodium spp. inside the erythrocyte. Once inside the red blood cell, malaria parasites cause extensive changes in the host cell, increasing membrane rigidity and altering its normal discoid shape. Additionally, during their intraerythrocytic development, malaria parasites incorporate and degrade up to 70 % of host cell hemoglobin. This mechanism is essential for parasite development and represents an important drug target. Blocking the steps related to hemoglobin endocytosis or degradation impairs parasite development and can lead to its death. The ultrastructural analysis of hemoglobin endocytosis on Plasmodium spp. has been broadly explored along the years. However, it is only recently that the proteins involved in this process have started to emerge. Here, we will review the most important features related to hemoglobin endocytosis and catabolism on malaria parasites. A special focus will be given to the recent analysis obtained through 3D visualization approaches and to the molecules involved in these mechanisms.

Diseases caused by protozoan parasites, such as leishmaniasis, trypanosomiasis, and malaria, are highly complex and together continue to cause high annual morbidity and mortality. The search for new compounds in environmental biodiversity, repositioning known drugs, and developing vaccines using old and innovative technologies have been employed to discover vaccines and new and alternative treatments. Extracellular vesicles (EVs) can carry parasite antigens, creating a new possibility to develop an effective and affordable platform for treatment, vaccines, and drug delivery. Thus, the evaluation of EVs in animal models can and should be explored among the countless biomedical applications. Herein, we will address the concept of EVs, their acquisition and characterization in protozoan parasite models, and the primary studies using these vesicles in therapeutic applications.

Bacterial extracellular vesicles (EVs) are cell-derived particles with a phospholipidic bilayer structure and diameter ranging from 20 to 250 nm, comprising a varied of components, including bioactive proteins, lipids, DNA, RNA, and other metabolites. These EVs play an essential role in bacterial and host function and are recognized as essential keys in cell-to-cell communication and pathogenesis. Due to these characteristics and functions, EVs exhibit great potential for biomedical applications and are promising tools for the development of drug delivery systems and vaccines, as well as for use in disease diagnostics. An interesting focus of this review is on the clinical relevance of EVs, with a particular emphasis on two critical pathogens, Acinetobacter baumannii and Klebsiella pneumoniae. Insights into the outer membrane vesicles (OMVs) derived from these bacteria underscore their roles in antimicrobial resistance and pathogenicity. Additionally, the review explores OMV-based vaccine strategies as a promising means to mitigating these pathogens.

Endothelial glycocalyx is a negatively charged gel-like layer located on the apical surface of endothelial cells. It serves as a selective two-way physical barrier between the flowing blood and the endothelium, which regulates the access of macromolecules and of blood cells to the endothelial surface. In addition, endothelial glycocalyx plays a major role in sensing mechanical signals generated by the blood flow and transducing these signals to maintain endothelial functions; Thus, dysfunction or disruption of endothelial glycocalyx in pathological condition leads to endothelial dysfunction and contributes to the development of vascular diseases. In this review, we discuss the impact of atherosclerosis with the following viewpoints: (i) hypercholesterolemic effects on endothelial glycocalyx degradation in animal models and human patients, (ii) disruption of endothelial glycocalyx by atherogenic lipoproteins, (iii) proatherogenic disturbed flow effects on endothelial glycocalyx degradation, (iv) pathological consequences of the loss of glycocalyx integrity in atherogenesis, and (v) therapeutic effect of glycocalyx supplementation on atherosclerosis development. Additionally, we also discuss recent studies in pathological effects of obesity on the disruption of endothelial glycocalyx.

The glycocalyx is a layer composed of carbohydrate side chains bound to core proteins that lines the vascular endothelium. The integrity of the glycocalyx is essential for endothelial cells' performance and vascular homeostasis. The neuroendocrine and immune systems influence the composition, maintenance, activity and degradation of the endothelial glycocalyx. The female organism has unique characteristics, and estrogen and progesterone, the main female hormones are essential to the development and physiology of the reproductive system and to the ability to develop a fetus. Female sex hormones also exert a wide variety of effects on other organs, including the vascular endothelium. They upregulate nitric oxide synthase expression and activity, decrease oxidative stress, increase vasodilation, and protect from vascular injury. This review will discuss how female hormones and pregnancy, which prompts to high levels of estrogen and progesterone, modulate the endothelial glycocalyx. Diseases prevalent in women that alter the glycocalyx, and therapeutic forms to prevent glycocalyx degradation and potential treatments that can reconstitute its structure and function will also be discussed.

The immune system is capable of identifying and eliminating cancer, a complicated illness marked by unchecked cellular proliferation. The significance of ion channels in the complex interaction between the immune system and cancer has been clarified by recent studies. Ion channels, which are proteins that control ion flow across cell membranes, have variety of physiological purposes, such as regulating immune cell activity and tumor development. Immune cell surfaces contain ion channels, which have been identified to control immune cell activation, motility, and effector activities. The regulation of immune responses against cancer cells has been linked to a number of ion channels, including potassium, calcium, and chloride channels. As an example, potassium channels are essential for regulating T cell activation and proliferation, which are vital for anti-tumor immunity. Calcium channels play a crucial role when immune cells produce cytotoxic chemicals in order to eliminate cancer cells. Chloride channels also affect immune cell infiltration and invasion into malignancies. Additionally, tumor cells' own expressed ion channels have an impact on their behavior and in the interaction with the immune system. The proliferation, resistance to apoptosis, and immune evasion of cancer cells may all be impacted by changes in ion channel expression and function. Ion channels may also affect the tumor microenvironment by controlling angiogenesis, inflammatory responses, and immune cell infiltration. Ion channel function in the interaction between the immune system and cancer has important implications for cancer treatment. A possible method to improve anti-tumor immune responses and stop tumor development is to target certain ion channels. Small compounds and antibodies are among the ion channel modulators under investigation as possible immunotherapeutics. The complex interaction between ion channels, the immune system, and cancer highlights the significance of these channels for tumor immunity. The development of novel therapeutic strategies for the treatment of cancer will be made possible by unraveling the processes by which ion channels control immune responses and tumor activity. Hence, the main driving idea of the present chapter is trying to understand the possible function of ion channels in the complex crosstalk between cancer and immunoresponse. To this aim, after giving a brief journey of ion channels throughout the history, a classification of the main ion channels involved in cancer disease will be discussed. Finally, the last paragraph will focus on more recently advancements in the use of biomaterials as therapeutic strategy for cancer treatment. The hope is that future research will take advantage of the promising combination of ion channels, immunomodulation and biomaterials filed to provide better solutions in the treatment of cancer disease.

Ion channels play a crucial role in cellular signaling, homeostasis, and generation of electrical and chemical signals. Aberrant expression and dysregulation of ion channels have been associated with cancer development and resistance to conventional cancer treatment such as chemotherapy. Several molecular mechanisms have been proposed to explain this phenomenon. Including evasion of apoptosis, decreased drug accumulation in cancer cells, detoxifying and activation of alternative escape pathways such as autophagy. Each of these mechanisms leads to a reduction of the therapeutic efficacy of administered drugs, causing more difficulty in cancer treatment. This review highlights the linkages between ion channels and resistance to chemotherapy. Furthermore, it elaborates their molecular mechanisms and the potential of being therapeutic targets in clinical management.

Sodium (Na⁺) concentration in solid tumours of different origin is highly dysregulated, and this corresponds to the aberrant expression of Na⁺ transporters. In particular, the α subunits of voltage gated Na⁺ channels (VGSCs) raise intracellular Na⁺ concentration ([Na⁺]_i) in malignant cells, which influences the progression of solid tumours, predominantly driving cancer cells towards a more aggressive and metastatic phenotype. Conversely, re-expression of VGSC β subunits in cancer cells can either enhance tumour progression or promote anti-tumourigenic properties. Metastasis is the leading cause of cancer-related mortality, highlighting an important area of research which urgently requires improved therapeutic interventions. Here, we review the extent to which VGSC subunits are dysregulated in solid tumours, and consider the implications of such dysregulation on solid tumour progression. We discuss current understanding of VGSC-dependent mechanisms underlying increased invasive and metastatic potential of solid tumours, and how the complex relationship between the tumour microenvironment (TME) and VGSC expression may further drive tumour progression, in part due to the interplay of infiltrating immune cells, cancer-associated fibroblasts (CAFs) and insufficient supply of oxygen (hypoxia). Finally, we explore past and present clinical trials that investigate utilising existing VGSC modulators as potential pharmacological options to support adjuvant chemotherapies to prevent cancer recurrence. Such research demonstrates an exciting opportunity to repurpose therapeutics in order to improve the disease-free survival of patients with aggressive solid tumours.

The endothelial glycocalyx (EG) is a gel-like structure that forms a layer in between the surface of the endothelium and lumen. EG was once thought to be merely a structural support for the endothelium. However, in recent years, the importance of EG as a first line of defense and a key regulator to endothelial integrity has been illuminated. With advanced age, EG deterioration becomes more noticeable and at least partially associated with endothelial dysfunction. Hyaluronan (HA), one of the critical components of the EG, has distinct properties and roles to the maintenance of EG and endothelial function. Therefore, given the intimate relationship between the EG and endothelium during the aging process, HA may serve as a promising therapeutic target to prevent endothelial dysfunction.