Nephron-Specific Overexpression Triggers Severe Inflammatory Response and Kidney Damage.

The RNA-binding proteins LIN28A and LIN28B contribute to a variety of developmental biological processes. Dysregulation of and expression is associated with numerous types of tumors. This study demonstrates that overexpression in the mouse nephrons leads to severe inflammation and kidney damage rather than to tumorigenesis.

Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome.

Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a low-fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet.

Critical Sites on Ostreolysin Are Responsible for Interaction with Cytoskeletal Proteins.

We explored the structural features of recombinant ostreolysin A (rOlyA), a protein produced by and responsible for binding to α/β-tubulin. We found that rOlyA cell internalization is essential for the induction of adipocyte-associated activity, which is mediated by the interaction of rOlyA and microtubule proteins. We created different point mutations at conserved tryptophan (W) sites in rOlyA and analyzed their biological activity in HIB-1B preadipocytes.

An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells.

The Dynamics of Lamin a During the Cell Cycle.

Lamin proteins play an essential role in maintaining the nuclear organization and integrity; and lamin A, in particular, plays a major role in the whole volume of the nuclear interior. Although the nucleus is highly organized, it is rather dynamic, it affects crucial nuclear processes and its organization must change as cells progress through the cell cycle. Although many aspects of these changes are already known, the role of lamin A during nuclear assembly and disassembly as well as its underlying mechanisms remains controversial.

Dose optimisation for Loss of Response to Vedolizumab- Pharmacokinetics and Immune Mechanisms.

Background: Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations.

Methods: A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients.

TMF1 is upregulated by insulin and is required for a sustained glucose homeostasis.

Insulin-regulated glucose homeostasis is a critical and intricate physiological process, of which not all regulatory components have been deciphered. One of the key players in modulating glucose uptake by cells is the glucose transporter-GLUT4. In this study, we aimed to explore the regulatory role of the trans-Golgi-associated protein-TATA Element Modulatory Factor (TMF1) in the GLUT4 mediated, insulin-directed glucose uptake.

Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages.

Cannabis sativa is widely used for medical purposes and has anti-inflammatory activity. This study intended to examine the anti-inflammatory activity of cannabis on immune response markers associated with coronavirus disease 2019 (COVID-19) inflammation. An extract fraction from C.

Carbon nanostructures as a scaffold for human embryonic stem cell differentiation toward photoreceptor precursors.

Carbon nanomaterials have been introduced as a scaffold for various biological applications due to their unique physical and electrical properties. Here we studied carbon nanotubes (CNTs) and carbon nanofibers (CNFs) as scaffold materials for the differentiation of human embryonic stem cells (hESCs) towards photoreceptor precursor cells (PRPs). We report on their cytoxicity, their effect on cell morphology, cell-surface interface and the differentiation process.

The Sub-Nuclear Localization of RNA-Binding Proteins in KSHV-Infected Cells.

RNA-binding proteins, particularly splicing factors, localize to sub-nuclear domains termed nuclear speckles. During certain viral infections, as the nucleus fills up with replicating virus compartments, host cell chromatin distribution changes, ending up condensed at the nuclear periphery. In this study we wished to determine the fate of nucleoplasmic RNA-binding proteins and nuclear speckles during the lytic cycle of the Kaposi's sarcoma associated herpesvirus (KSHV).

Characterization of PfiT/PfiA toxin-antitoxin system of Pseudomonas aeruginosa that affects cell elongation and prophage induction.

Toxin-antitoxin (TA) systems are small genetic modules usually consisting of two elements-a toxin and an antitoxin. The abundance of TA systems among various bacterial strains may indicate an important evolutionary role. Pseudomonas aeruginosa, which can be found in a variety of niches in nature, is an opportunistic pathogen for various hosts.

A single nucleotide variant of human PARP1 determines response to PARP inhibitors.

The introduction of novel cancer drugs and innovative treatments brings great hope for cancer patients, but also an urgent need to match drugs to suitable patients, since certain drugs that benefit one patient may actually harm others. The newly developed poly-ADP ribose polymerase (PARP) inhibitors (PARPis) are a group of pharmacological enzyme inhibitors used clinically for multiple indications. Several forms of cancer tend to be PARP dependent, making PARP an attractive target for cancer therapy.

Type Three Secretion System-Dependent Microvascular Thrombosis and Ischemic Enteritis in Human Gut Xenografts Infected with Enteropathogenic Escherichia coli.

Enteropathogenic (EPEC) is a leading cause of severe intestinal disease and infant mortality in developing countries. Virulence is mediated by a type three secretion system (T3SS), causing the hallmark attaching and effacing (AE) lesions and actin-rich pedestal formation beneath the infecting bacteria on the apical surface of enterocytes. EPEC is a human-specific pathogen whose pathogenesis cannot be studied in animal models.

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease.

Background And Aim: Thymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn's disease (CD).

Antagonistic activities of Rho and Rac GTPases underlie the transition from neural crest delamination to migration.

Background: Neural crest progenitors arise as epithelial cells and then undergo a transition into mesenchyme that generates motility. Previously, we showed that active Rho maintains crest cells in the epithelial conformation by keeping stress fibers and membrane-bound N-cadherin.

Results: While Rho disappears from cell membranes upon delamination, active Rac1 becomes apparent in lamellipodia of mesenchymal cells.

A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells.

Background: Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade.

Development and validation of a Patient-Reported Oral Mucositis Symptom (PROMS) scale.

Background And Objective: Oral mucositis, a painful condition with potentially life-threatening sequelae, often develops in association with allogeneic bone marrow transplantation. This condition has an adverse impact on the oral-health-related quality of life of patients undergoing marrow transplantation therapy. The purpose of this study was to create and validate a Patient-Reported Oral Mucositis Symptom (PROMS) scale.

Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination.

During neural crest ontogeny, an epithelial to mesenchymal transition is necessary for cell emigration from the dorsal neural tube. This process is likely to involve a network of gene activities, which remain largely unexplored. We demonstrate that N-cadherin inhibits the onset of crest delamination both by a cell adhesion-dependent mechanism and by repressing canonical Wnt signaling previously found to be necessary for crest delamination by acting downstream of BMP4.