Polarizing intestinal epithelial cells electrically through Ror2

© 2014. Published by The Company of Biologists Ltd.Peer reviewedPublisher PD

A Comprehensive Model of the Spatio-Temporal Stem Cell and Tissue Organisation in the Intestinal Crypt

We introduce a novel dynamic model of stem cell and tissue organisation in murine intestinal crypts. Integrating the molecular, cellular and tissue level of description, this model links a broad spectrum of experimental observations encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal competition

Human-Derived Model Systems in Gynecological Cancer Research

The human female reproductive tract (FRT) is a complex system that combines series of organs, including ovaries, fallopian tubes, uterus, cervix, vagina, and vulva; each of which possesses unique cellular characteristics and functions. This versatility, in turn, allows for the development of a wide range of epithelial gynecological cancers with distinct features. Thus, reliable model systems are required to better understand the diverse mechanisms involved in the regional pathogenesis of the reproductive tract and improve treatment strategies. Here, we review the current human-derived model systems available to study the multitude of gynecological cancers, including ovarian, endometrial, cervical, vaginal, and vulvar cancer, and the recent advances in the push towards personalized therapy

Gut Microbiota in Colorectal Cancer: Associations, Mechanisms, and Clinical Approaches

Colorectal cancer (CRC) is associated with the presence of particular gut microbes, as observed in many metagenomic studies to date. However, in most cases, it remains difficult to disentangle their active contribution to CRC from just a bystander role. This review focuses on the mechanisms described to date by which the CRC-associated microbiota could contribute to CRC. Bacteria like pks+ Escherichia coli, Fusobacterium nucleatum, or enterotoxigenic Bacteroides fragilis have been shown to induce mutagenesis, alter host epithelial signaling pathways, or reshape the tumor immune landscape in several experimental systems. The mechanistic roles of other bacteria, as well as newly identified fungi and viruses that are enriched in CRC, are only starting to be elucidated. Additionally, novel systems like organoids and organs-on-a-chip are emerging as powerful tools to study the direct effect of gut microbiota on healthy or tumor intestinal epithelium. Thus, the expanding knowledge of tumor-microbiota interactions holds promise for improved diagnosis and treatment of CRC

The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Traditional therapeutic approaches such as chemotherapy or radiotherapy have provided only a marginal improvement in the treatment of lung carcinomas. Inhibitors targeting specific genetic aberrations present in non-small cell lung cancer (NSCLC), the most common subtype (85%), have improved the prognostic outlook, but due to the complexity of the LC mutational spectrum, only a fraction of patients benefit from these targeted molecular therapies. More recently, the realization that the immune infiltrate surrounding solid tumors can foster tumor-promoting inflammation has led to the development and implementation of anticancer immunotherapies in the clinic. In NSCLC, one of the most abundant leukocyte infiltrates is macrophages. These highly plastic phagocytes, which are part of the cellular repertoire of the innate immunity, can have a pivotal role in early NSCLC establishment, malignant progression, and tumor invasion. Emerging macrophage-targeting therapies have been focused on the re-differentiation of the macrophages toward an antitumori-genic phenotype, depletion of tumor-promoting macrophage subtypes, or combination therapies combining traditional cytotoxic treatments with immunotherapeutic agents. The most extensively used models employed for the exploration of NSCLC biology and therapy have been 2D cell lines and murine models. However, studying cancer immunology requires appropriately complex models. 3D platforms, including organoid models, are quickly advancing powerful tools to study immune cell-epithelial cell interactions within the tumor microenvironment. Co-cultures of immune cells along with NSCLC organoids allow for an in vitro observation of the tumor microenvironment dynamics closely resembling in vivo settings. Ultimately, the implementation of 3D organoid technology into tumor microenvironment-modeling platforms might facilitate the exploration of macrophage-targeted therapies in NSCLC immunotherapeutic research, thus establishing a new frontier in NSCLC treatment

Формування політичних інститутів в країнах Центральної Азії в умовах незалежності

Останні досягнення і соціально-економічні успіхи країн Центральної Азії, що отримали незалежність з розпадом СРСР ґрунтуються на багатьох чинниках, серед яких, у першу чергу, проведення ефективних економічних реформ, становлення середнього класу і формування зрілого суспільства

Лексичні дублети у «Російсько-українському словнику» 1924-33 рр.

Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists

A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome

Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-map(TM) dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS