Inhibition of glycolysis and Src/Akt signaling reduces Caveolin-1-enhanced metastasis.

Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis.

Co-Culture of . and . Synergistically Elevates IL-6 Expression via TLR4 Signaling in Oral Keratinocytes.

Periodontitis, characterized by persistent inflammation in the periodontium, is intricately connected to systemic diseases, including oral cancer. Bacteria, such as and , play a pivotal role in periodontitis development because they contribute to dysbiosis and tissue destruction. Thus, comprehending the interplay between these bacteria and their impacts on inflammation holds significant relevance in clinical understanding and treatment advancement.

Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models.

Caveolin-1 (CAV1) is a membrane-bound protein that suppresses tumor development yet also promotes metastasis. E-cadherin is important in CAV1-dependent tumor suppression and prevents CAV1-enhanced lung metastasis. Here, we used murine B16F10 and human A375 melanoma cells with low levels of endogenous CAV1 and E-cadherin to unravel how co-expression of E-cadherin modulates CAV1 function in vitro and in vivo in WT C57BL/6 or Rag-/- immunodeficient mice and how a pro-inflammatory environment generated by treating cells with prostaglandin E2 (PGE2) alters CAV1 function in the presence of E-cadherin.

HERPUD1 governs tumor cell mitochondrial function via inositol 1,4,5-trisphosphate receptor-mediated calcium signaling.

The intricate relationship between calcium (Ca) homeostasis and mitochondrial function is crucial for cellular metabolic adaptation in tumor cells. Ca-initiated signaling maintains mitochondrial respiratory capacity and ATP synthesis, influencing critical cellular processes in cancer development. Previous studies by our group have shown that the homocysteine-inducible ER Protein with Ubiquitin-Like Domain 1 (HERPUD1) regulates inositol 1,4,5-trisphosphate receptor (ITPR3) levels and intracellular Ca signals in tumor cells.

The Anti-Oxidant Curcumin Solubilized as Oil-in-Water Nanoemulsions or Chitosan Nanocapsules Effectively Reduces Growth, Bacterial Biofilm Formation, Gastric Cell Adhesion and Internalization.

The bacterium () represents a major risk factor associated with the development of gastric cancer. The anti-oxidant curcumin has been ascribed many benefits to human health, including bactericidal effects. However, these effects are poorly reproducible because the molecule is extremely unstable and water insoluble.

Inhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis.

Purpose: Oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, referred to as oral dysplasia. We recently reported that oral dysplasia is associated with aberrant activation of the Wnt/β-catenin pathway, due to overexpression of Wnt ligands in a Porcupine (PORCN)-dependent manner. Pharmacologic inhibition of PORCN precludes Wnt secretion and has been proposed as a potential therapeutic approach to treat established cancers.

Phlorotannins: Novel Orally Administrated Bioactive Compounds That Induce Mitochondrial Dysfunction and Oxidative Stress in Cancer.

Mitochondrial dysfunction is an interesting therapeutic target to help reduce cancer deaths, and the use of bioactive compounds has emerged as a novel and safe approach to solve this problem. Here, we discuss the information available related to phlorotannins, a type of polyphenol present in brown seaweeds that reportedly functions as antioxidants/pro-oxidants and anti-inflammatory and anti-tumorigenic agents. Specifically, available evidence indicates that dieckol and phloroglucinol promote mitochondrial membrane depolarization and mitochondria-dependent apoptosis.

Helicobacter pylori outer membrane vesicles induce astrocyte reactivity through nuclear factor-κappa B activation and cause neuronal damage in vivo in a murine model.

Background: Helicobacter pylori (Hp) infects the stomach of 50% of the world's population. Importantly, chronic infection by this bacterium correlates with the appearance of several extra-gastric pathologies, including neurodegenerative diseases. In such conditions, brain astrocytes become reactive and neurotoxic.

The Adipocyte-Macrophage Relationship in Cancer: A Potential Target for Antioxidant Therapy.

Obesity has emerged as a major public health concern with a staggering 39% worldwide prevalence as of 2021. Given the magnitude of the problem and considering its association with chronic low-grade systemic inflammation, it does not come as a surprise that obesity is now considered one of the major risk factors for the development of several chronic diseases, such as diabetes, cardiovascular problems, and cancer. Adipose tissue dysfunction in obesity has taken center stage in understanding how changes in its components, particularly adipocytes and macrophages, participate in such processes.

Polycystin-1 Is a Crucial Regulator of BIN1 Expression and T-Tubule Remodeling Associated with the Development of Dilated Cardiomyopathy.

Cardiomyopathy is commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD), even when they have normal renal function and arterial pressure. The role of cardiomyocyte polycystin-1 (PC1) in cardiovascular pathophysiology remains unknown. PC1 is a potential regulator of BIN1 that maintains T-tubule structure, and alterations in BIN1 expression induce cardiac pathologies.

Protein kinase B (AKT) upregulation and Thy-1-αβ integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

Background: In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αβ integrin.

Extracellular vesicles from gastric epithelial GES-1 cells infected with promote changes in recipient cells associated with malignancy.

Chronic () infection is considered the main risk factor for the development of gastric cancer. Pathophysiological changes in the gastric mucosa initiated by this bacterium can persist even after pharmacological eradication and are likely attributable also to changes induced in non-infected cells as a consequence of intercellular communication extracellular vesicles (EVs). To better understand what such changes might entail, we isolated EVs from immortalized normal gastric GES-1 cells infected (EVHp+) or not with (EVHp-) by ultracentrifugation and characterized them.

The GPI-Anchored Protein Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin by Enhancing Skin Perfusion.

Wound healing is a highly regulated multi-step process that involves a plethora of signals. Blood perfusion is crucial in wound healing and abnormalities in the formation of new blood vessels define the outcome of the wound healing process. Thy-1 has been implicated in angiogenesis and silencing of the Thy-1 gene retards the wound healing process.

co-incubation enhances virulence and increases migration of infected human oral keratinocytes.

Background: is part of the subgingival biofilm and a keystone species in the development of periodontitis. Interactions between and other bacteria in biofilms have been shown to affect bacterial virulence. also inhabits the subgingival biofilm, but the consequences of interactions there with remain unknown.

Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis.

Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV.

Role of the Pro-Inflammatory Tumor Microenvironment in Extracellular Vesicle-Mediated Transfer of Therapy Resistance.

Advances in our understanding of cancer biology have contributed to generating different treatments to improve the survival of cancer patients. However, although initially most of the therapies are effective, relapse and recurrence occur in a large percentage of these cases after the treatment, and patients then die subsequently due to the development of therapy resistance in residual cancer cells. A large spectrum of molecular and cellular mechanisms have been identified as important contributors to therapy resistance, and more recently the inflammatory tumor microenvironment (TME) has been ascribed an important function as a source of signals generated by the TME that modulate cellular processes in the tumor cells, such as to favor the acquisition of therapy resistance.

Small RNA Expression Profiling Reveals hsa-miR-181d-5p Downregulation Associated With TNF-α Overexpression in Sjögren's Syndrome Patients.

MicroRNAs (miRNAs) are small non-coding RNAs (sRNA), that alter gene expression by binding to target messenger RNAs (mRNAs) and repressing translation. Dysregulated miRNA expression has been implicated in the pathogenesis of autoimmune diseases such as Sjögren's syndrome (SS). The aim of this study was to characterize the global profile of sRNAs in labial salivary glands (LSG) from SS-patients and to validate potential miRNA candidates implicated in glandular inflammation.

Experimental design and optimization of a novel dual-release drug delivery system with therapeutic potential against infection with Helicobacter pylori.

The objective of this study was to develop clarithromycin-loaded lipid nanocarriers and incorporate them into microcapsules for pH-specific localized release of clarithromycin in the Helicobacter pylori microenvironment in order to obtain a gastro-retentive and pH-sensitive formulation. A Plackett-Burman design was applied to identify the effect of 5 factors on 3 responses. Then, a central composite design was applied to estimate the most important factors leading to the best compromise between lower particle size, polydispersity index and particle size changes.

A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo.

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action.

Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications.

Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer.

Outer Membrane Vesicles and Extracellular Vesicles from -Infected Cells in Gastric Disease Development.

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with () is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component.

Perspectives on Organelle Interaction, Protein Dysregulation, and Cancer Disease.

In recent decades, compelling evidence has emerged showing that organelles are not static structures but rather form a highly dynamic cellular network and exchange information through membrane contact sites. Although high-throughput techniques facilitate identification of novel contact sites (e.g.