Multivesicular

Overexpression of the transmembrane matrix metalloproteinase MT1-MMP/MMP14 promotes cancer cell invasion. Here we show that MT1-MMP-positive cancer cells turn MT1-MMP-negative cells invasive by transferring a soluble catalytic ectodomain of MT1-MMP. Surprisingly, this effect depends on the presence of TKS4 and TKS5 in the donor cell, adaptor proteins previously implicated in invadopodia formation. In endosomes of the donor cell, TKS4/5 promote ADAM-mediated cleavage of MT1-MMP by bridging the two proteases, and cleavage is stimulated by the low intraluminal pH of endosomes...

Neuropathy is a serious and frequent complication of type 2 diabetes (T2DM). This study was carried out to search for genetic factors associated with the development of diabetic neuropathy by whole exome sequencing. For this study, 24 patients with long-term type 2 diabetes with neuropathy and 24 without underwent detailed neurological assessment and whole exome sequencing. Cardiovascular autonomic function was evaluated by cardiovascular reflex tests. Heart rate variability was measured by the triangle index...

Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite the consumption of the limiting membrane during ILV formation...

Adenosine monophosphate-activated protein kinase (AMPK), the central energy sensor in more complex eukaryotes, can activate macroautophagy/autophagy upon cellular energy deficiency. However, the regulatory role of nutrient sensing in mediating phagophore closure to generate an autophagosome remains unknown. The evolutionarily conserved endosomal sorting complexes required for transport (ESCRT) machinery has been postulated to regulate phagophore sealing, yet the signaling pathway modulating the ESCRT complex relocation from multivesicular body (MVB) to phagophore for closure remains unknown...

INTRODUCTION: Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin condition. In Malaysia, a prevalence of 13.4% was reported for children between one and six years of age, one of the highest prevalence rates of AD in Asia. Many guidelines recommended moisturisers as the mainstay of treatment strategy for AD. Selecting an effective and suitable moisturiser for people with AD plays a crucial role in avoiding acute exacerbation of AD and achieving remission. MATERIALS AND METHODS: Given that an array of active ingredients and topical vehicles for moisturisers are available in the market, this review summarised the roles of ceramides and multivesicular emulsion (MVE) technology in managing AD to help guide treatment decisions...

In nature, the formation of specialized (secondary) metabolites is associated with the late stages of fungal development. Enzymes involved in the biosynthesis of secondary metabolites in fungi are located in distinct subcellular compartments including the cytosol, peroxisomes, endosomes, endoplasmic reticulum, different types of vesicles, the plasma membrane and the cell wall space. The enzymes traffic between these subcellular compartments and the secretion through the plasma membrane are still unclear in the biosynthetic processes of most of these metabolites...

A healthy bladder requires the homeostatic maintenance of and rapid regeneration of urothelium upon stress/injury/infection. Several factors have been identified to play important roles in urothelial development, injury and disease response, however, little is known about urothelial regulation at homeostasis. Here, we identify a new role for IFRD1, a stress-induced gene that has recently been demonstrated to play a critical role in adult tissue proliferation and regeneration, in maintenance of urothelial function/ homeostasis in a mouse model...

Wnt signaling is essential for embryonic development, influencing processes such as axis formation, cell proliferation and differentiation, cell fate decisions, and axon guidance. It also plays a role in maintaining tissue homeostasis in adult organisms. The loss of normal cell polarity and adhesion caused by Wnt signaling activation is a fundamental step for tumor progression and metastasis. Activating the canonical Wnt pathway is a driving force in many human cancers, especially colorectal, hepatocellular, and mammary carcinomas...

The donkey's extraordinary capacity to endure substantial loads over long distances while maintaining equilibrium suggests a distinctive cerebellar architecture specialized in balance regulation. Consequently, our study aims to investigate the intricate histophysiology of the donkey's cerebellum using advanced ultrastructural and immunohistochemical methodologies to comprehend the mechanisms that govern this exceptional ability. This study represents the pioneering investigation to comprehensively describe the ultrastructure and immunohistochemistry within the donkey cerebellum...

BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the E×4formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified E×4(Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection. METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process...

PURPOSE: A multivesicular liposome (MVL) is a liposomal vehicle designed to achieve sustained release characteristics for drugs with short half-lives. For example, a commercial MVL formulation of bupivacaine has been approved by the U.S. Food and Drug Administration for local and regional analgesia. For complex formulations like those containing MVLs, challenges in developing an in vitro release testing (IVRT) method may hinder generic development and regulatory approval. In this study, we developed an accelerated rotator-based IVRT method with the ability to discriminate bupivacaine MVLs with different quality attributes...

The role of autophagy in pulmonary microvascular endothelial cell (PMVEC) are controversial in lipopolysaccharide (LPS)-induced ALI. Mixed lineage kinase domain like pseudokinase (MLKL) has been recently reported to keep cell survival by facilitating autophagic flux in response to starvation, rather than its well-recognized role in necroptosis. Using mouse PMVEC and LPS-induced ALI model, we showed that in PMVEC, MLKL was phosphorylated (p-MLKL) and autophagic flux was accelerated at the early stage of LPS stimulation (1-3 h), manifested by increases in levels of lipidated MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta; LC3-II), decreases in levels of SQSTM1/p62 (sequestosome 1), and fusion of autophagosome and lysosome by pHluorin-mKate2-human LC3 assay, which were all reversed by either MLKL inhibitor or siRNA MLKL...

Charged multivesicular protein 1 (CHMP1) is a member of the ESCRT-III complex that targets membrane localized signaling receptors to intralumenal vesicles in the multivesicular body of the endosome and eventually to the lysosome for degradation. Although CHMP1 plays roles in various plant growth and development processes, little is known about its function in wheat. In this study, we systematically analyzed the members of the ESCRT-III complex and found that their orthologs were highly conserved in eukaryotic evolution...

Exosomes, a type of extracellular vesicle with a diameter of approximately 100 nm that is secreted by all cells, regulate the phenotype and function of recipient cells by carrying molecules such as proteins, nucleic acids, and lipids and are important mediators of intercellular communication. Exosomes are involved in various physiological and pathological processes such as immunomodulation, angiogenesis, tumorigenesis, metastasis, and chemoresistance. Due to their excellent properties, exosomes have shown their potential application in the clinical diagnosis and treatment of disease...

BACKGROUND: A peculiar feature of the hepatitis E virus (HEV) is its reliance on the exosomal route for viral release. Genomic replication is mediated via the viral polyprotein pORF1, yet little is known about its subcellular localization. METHODS: Subcellular localization of pORF1 and its subdomains, generated and cloned based on a structural prediciton of the viral replicase, was analyzed via confocal laser scanning microscopy. Exosomes released from cells were isolated via ultracentrifugation and analyzed by isopycnic density gradient centrifugation...

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) is an immediate early gene that plays a vital role in learning and memory. The recent discovery that Arc mediates the inter-neuronal RNA transfer implies its role in regulating neuronal functions across long distances. Arc protein has structural and functional properties similar to viral Group-specific antigen (Gag). By assembling into high-order, virus-like capsids, Arc mediates the intercellular RNA transfer. However, the exact secretion pathway through which Arc capsids maneuver cargos is unclear...

Breast cancer (BC) is the most prevalent malignancy among women worldwide. Mounting evidence suggests that PANoptosis participates in cancer development and therapy. However, the role of PANoptosis in BC remains unclear. In this study, we identified ten PANoptosis-related genes using Cox regression analysis, random forest (RF) algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. A PANoptosis-related score (PRS) was calculated based on the coefficient of LASSO. Notably, we divided the patients into high- and low-risk groups according to the PRS and revealed a negative correlation between PRS and overall survival...

Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication...

Hepatitis C virus (HCV) is a positive-sense, single-stranded RNA virus that causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The release of infectious HCV particles from infected hepatocytes is a crucial step in viral dissemination and disease progression. While the exact mechanisms of HCV particle release remain poorly understood, emerging evidence suggests that HCV utilizes intracellular membrane trafficking and secretory pathways. These pathways include the Golgi secretory pathway and the endosomal trafficking pathways, such as the recycling endosome pathway and the endosomal sorting complex required for transport (ESCRT)-dependent multivesicular bodies (MVBs) pathway...

INTRODUCTION AND IMPORTANCE: Hydatid cysts are a parasitic disease that occurs when humans ingest contaminated food or water containing parasitic eggs. It is a common disease worldwide, especially in cattle breeding areas. In rare cases, the primary cysts contain daughter cysts inside them, as seen in this case. CASE PRESENTATION: We report a 28-year-old rural woman who presented with a history of sputum-producing cough, dyspnea, hemoptysis, and pain in the right side of the chest...