Novel humanized anti-PcrV monoclonal antibody COT-143 protects mice from lethal infection via inhibition of toxin translocation by the type III secretion system.

Treatment of infection is challenging due to its intrinsic and acquired antibiotic resistance. As the number of current therapeutic options for infections is limited, developing novel treatments against the pathogen is an urgent clinical priority. The suppression of virulence of could be a new therapeutic option, and the type III secretion system (T3SS), which enables the bacteria to translocate various kinds of toxins into host cells and inhibits cellular functions, is considered as one possible target.

Possible involvement of zinc transporter ZIP13 in myogenic differentiation.

Ehlers-Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.

Prognostic impact of radiological tumor burden in patients with metastatic urothelial carcinoma treated with pembrolizumab.

Purpose: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC.

Methods: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab.

Zinc in Cardiovascular Functions and Diseases: Epidemiology and Molecular Mechanisms for Therapeutic Development.

Zinc is an essential trace element that plays an important physiological role in numerous cellular processes. Zinc deficiency can result in diverse symptoms, such as impairment of the immune response, skin disorders, and impairments in cardiovascular functions. Recent reports have demonstrated that zinc acts as a signaling molecule, and its signaling pathways, referred to as zinc signals, are related to the molecular mechanisms of cardiovascular functions.

Role of Scl39a13/ZIP13 in cardiovascular homeostasis.

Zinc plays a critical role in many physiological processes, and disruption of zinc homeostasis induces various disorders, such as growth retardation, osteopenia, immune deficiency, and inflammation. However, how the imbalance in zinc homeostasis leads to heart disease is not yet fully understood. Cardiovascular diseases are a major cause of death worldwide, and the development of novel therapeutic targets to treat it is urgently needed.

Zinc transporters as potential therapeutic targets: An updated review.

Zinc is an essential trace element that plays important roles in the regulation of various physiological responses in the body. Zinc deficiency is known to cause various health problems, including dysgeusia, skin disorders, and immune disorders. Therefore, the maintenance of healthy zinc content in the body is critical to our healthy life.

Developments of real-time emittance monitors.

Under the upgrade program of an azimuthally varying field (AVF) cyclotron in progress at the Research Center for Nuclear Physics (RCNP), an emittance monitor is being developed to improve the beam injection efficiency from ion sources to the AVF cyclotron. In order to evaluate the quality of the beams extracted from ion sources quickly, we developed the Pepper-Pot type Emittance Monitor at the RCNP. After improving an analysis method for emittance estimation using LabVIEW, we achieved a measurement frequency of 4 Hz.

Anti-PcrV titers in non-cystic fibrosis patients with Pseudomonas aeruginosa respiratory tract infection.

Objective: The epidemiology and role of the anti-PcrV titer in non-cystic fibrosis patients with Pseudomonas aeruginosa airway tract infections is not fully understood. This study was performed to compare the anti-PcrV titers of patients with and without P. aeruginosa respiratory tract infections.

Maintenance of Intestinal Epithelial Homeostasis by Zinc Transporters.

Zinc is an essential micronutrient for normal organ function, and dysregulation of zinc metabolism has been implicated in a wide range of diseases. Emerging evidence has revealed that zinc transporters play diverse roles in cellular homeostasis and function by regulating zinc trafficking via organelles or the plasma membrane. In the gastrointestinal tract, zinc deficiency leads to diarrhea and dysfunction of intestinal epithelial cells.

The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin.

The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders including acrodermatitis enteropathica (also known as Danbolt-Closs syndrome) and Brandt's syndrome are highly related to zinc deficiency. However, the zinc-related molecular mechanisms underlying normal skin development and homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes such skin disorders, are unknown.

Recent Advances in the Role of SLC39A/ZIP Zinc Transporters In Vivo.

Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular machineries and influences physiological events, such as systemic growth, bone homeostasis, skin formation, immune responses, endocrine function, and neuronal function. Zn transporters are thought to mainly contribute to Zn homeostasis within cells and in the whole body. Recent genetic, cellular, and molecular studies of Zn transporters highlight the dynamic role of Zn as a signaling mediator linking several cellular events and signaling pathways.

Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis.

Skin tissues, in particular the epidermis, are severely affected by zinc deficiency. However, the zinc-mediated mechanisms that maintain the cells that form the epidermis have not been established. Here, we report that the zinc transporter ZIP10 is highly expressed in the outer root sheath of hair follicles and plays critical roles in epidermal development.

Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase.

Skin is the first area that manifests zinc deficiency. However, the molecular mechanisms by which zinc homeostasis affects skin development remain largely unknown. Here, we show that zinc-regulation transporter-/iron-regulation transporter-like protein 7 (ZIP7) localized to the endoplasmic reticulum plays critical roles in connective tissue development.

Ligands at Free Fatty Acid Receptor 1 (GPR40).

FFA1 is a G protein-coupled receptor activated by medium- to long-chain fatty acids. FFA1 plays important roles in various physiological processes such as insulin secretion and energy metabolism. FFA1 expressed on pancreatic β-cells and intestine contributes to insulin and incretin secretion, respectively.

Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress.

Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation.

Mechanism of resistance and antibacterial susceptibility in extended-spectrum β-lactamase phenotype Klebsiella pneumoniae and Klebsiella oxytoca isolated between 2000 and 2010 in Japan.

Clinical isolates of Klebsiella pneumoniae and Klebsiella oxytoca collected from 20 Japanese medical facilities between 2000 and 2010 were analysed to evaluate the mechanisms of resistance and antibacterial susceptibilities to 14 antimicrobials. Overall, eight of 484 (1.6%) K.

Comparison of the risk of acquiring in vitro resistance to doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli.

To compare the risk of acquiring in vitro resistance between doripenem and tazobactam/piperacillin by CTX-M-15-producing Escherichia coli, the in vitro frequency of resistance was determined. Four strains carrying multiple β-lactamases such as blaOXA-1 or blaCTX-M-27 as well as blaCTX-M-15 and blaTEM-1 were used. No resistant colonies appeared on doripenem-containing plates, whereas resistant colonies were obtained from three of four test strains against tazobactam/piperacillin using agar plate containing 8- to 16-fold MIC of each drug.

Regulation of Energy Homeostasis via GPR120.

Free fatty acids (FFAs) are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs), activate intracellular signaling and exert physiological functions via these GPCRs.

Role of free fatty acid receptors in the regulation of energy metabolism.

Free fatty acids (FFAs) are energy-generating nutrients that act as signaling molecules in various cellular processes. Several orphan G protein-coupled receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play important physiological roles in various diseases. FFA ligands are obtained from food sources and metabolites produced during digestion and lipase degradation of triglyceride stores.