GPER expression prevents estrogen-induced urinary retention in obese mice.

Long-term administration of exogenous estrogen is known to cause urinary retention and marked, often fatal, bladder distention in both male and female mice. Estrogen-treated mice have increased bladder pressure and decreased urine flow, suggesting that urinary retention in estrogen-treated mice is due to infravesicular obstruction to urine outflow. Thus, the condition is commonly referred to as bladder outlet obstruction (BOO).

GPER deficiency impedes murine myocutaneous revascularization and wound healing.

Estrogens regulate numerous physiological and pathological processes, including wide-ranging effects in wound healing. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ER ), that typically regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), that predominantly mediates rapid "non-genomic" signaling. Estrogen modulates the expression of various genes involved in epidermal function and regeneration, inflammation, matrix production, and protease inhibition, all critical to wound healing.

Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer.

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known.

Using electrocardiogram electrodes to monitor skin impedance spectroscopic response when skin is subjected to sustained static pressure.

Background: Impedance spectroscopy is a non-invasive technique which can be used to monitor skin barrier function, with potential applications in early-stage pressure ulcer detection. This paper describes how changes in skin impedance, due to mechanical damage of the stratum corneum by tape stripping or applied pressure, can be straightforwardly measured using commercial electrocardiogram electrodes and a relatively low-cost impedance analyser. Two models of pressure injury were studied, an ex vivo porcine and in vivo human skin model.

mTORC2 Loss in Oligodendrocyte Progenitor Cells Results in Regional Hypomyelination in the Central Nervous System.

In the CNS, oligodendrocyte progenitor cells (OPCs) differentiate into mature oligodendrocytes to generate myelin, an essential component for normal nervous system function. OPC differentiation is driven by signaling pathways, such as mTOR, which functions in two distinct complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), containing Raptor or Rictor, respectively. In the current studies, mTORC2 signaling was selectively deleted from OPCs in PDGFRα-Cre X Rictor mice.

Assessment of mutations induced by cold atmospheric plasma jet treatment relative to known mutagens in Escherichia coli.

The main bactericidal components of cold atmospheric plasma (CAP) are thought to be reactive oxygen and nitrogen species (RONS) and UV-radiation, both of which have the capacity to cause DNA damage and mutations. Here, the mutagenic effects of CAP on Escherichia coli were assessed in comparison to X- and UV-irradiation. DNA damage and mutagenesis were screened for using a diffusion-based DNA fragmentation assay and modified Ames test, respectively.

Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence.

The mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically. During this nutritional paradigm, ME perineuronal nets (PNNs), emerging regulators of ARH metabolic functions, are rapidly remodeled, and this process requires myelin regulatory factor (Myrf) in oligodendrocyte progenitors.

A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections.

Infection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection.

Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties.

Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate, with concomitant oxidation of reduced nicotinamide adenine dinucleotide as the final step in the glycolytic pathway. Glycolysis plays an important role in the metabolic plasticity of cancer cells and has long been recognized as a potential therapeutic target. Thus, potent, selective inhibitors of LDH represent an attractive therapeutic approach.

Complement Receptor 3 Contributes to the Sexual Dimorphism in Neutrophil Killing of .

We previously reported sex differences in innate susceptibility to skin infection and that bone marrow neutrophils (BMN) from female mice have an enhanced ability to kill ex vivo compared with those of male mice. However, the mechanism(s) driving this sex bias in neutrophil killing have not been reported. Given the role of opsonins such as complement, as well as their receptors, in recognition and clearance, we investigated their contribution to the enhanced bactericidal capacity of female BMN.

Sex differences in murine myocutaneous flap revascularization.

Sex differences in susceptibility to ischemia/reperfusion injury have been documented in humans. Premenopausal women have a lower risk of ischemic heart disease than age-matched men, whereas after menopause, the risk is similar or even higher in women. However, little is known about the effects of sex on myocutaneous ischemia/reperfusion.

Preclinical efficacy of the GPER-selective agonist G-1 in mouse models of obesity and diabetes.

Human obesity has become a global health epidemic, with few safe and effective pharmacological therapies currently available. The systemic loss of ovarian estradiol (E2) in women after menopause greatly increases the risk of obesity and metabolic dysfunction, revealing the critical role of E2 in this setting. The salutary effects of E2 are traditionally attributed to the classical estrogen receptors ERα and ERβ, with the contribution of the G protein-coupled estrogen receptor (GPER) still largely unknown.

Reaction-based indicator displacement assay (RIA) for the development of a triggered release system capable of biofilm inhibition.

Here, a reaction-based indicator displacement hydrogel assay (RIA) was developed for the detection of hydrogen peroxide (H2O2) via the oxidative release of the optical reporter Alizarin Red S (ARS). In the presence of H2O2, the RIA system displayed potent biofilm inhibition for Methicillin-resistant Staphylococcus aureus (MRSA), as shown through an in vitro assay quantifying antimicrobial efficacy. This work demonstrated the potential of H2O2-responsive hydrogels containing a covalently bound diol-based drug for controlled drug release.

A Selective Ligand for Estrogen Receptor Proteins Discriminates Rapid and Genomic Signaling.

Estrogen exerts extensive and diverse effects throughout the body of women. In addition to the classical nuclear estrogen receptors (ERα and ERβ), the G protein-coupled estrogen receptor GPER is an important mediator of estrogen action. Existing ER-targeted therapeutic agents act as GPER agonists.

Investigating Wilms' Tumours Worldwide: A Report of the OxPLORE Collaboration-A Cross-Sectional Observational Study.

Background: Childhood cancer is neglected within global health. Oxford Pediatrics Linking Oncology Research with Electives describes early outcomes following collaboration between low- and high-income paediatric surgery and oncology centres. The aim of this paper is twofold: to describe the development of a medical student-led research collaboration; and to report on the experience of Wilms' tumour (WT).

Gut microbiome in serious mental illnesses: A systematic review and critical evaluation.

Schizophrenia and bipolar disorder (BD) are associated with debilitating psychiatric and cognitive dysfunction, worse health outcomes, and shorter life expectancies. The pathophysiological understanding of and therapeutic resources for these neuropsychiatric disorders are still limited. Humans harbor over 1000 unique bacterial species in our gut, which have been linked to both physical and mental/cognitive health.

GPER activation protects against epithelial barrier disruption by Staphylococcus aureus α-toxin.

Sex bias in innate defense against Staphylococcus aureus skin and soft tissue infection (SSTI) is dependent on both estrogen production by the host and S. aureus secretion of the virulence factor, α-hemolysin (Hla). The impact of estrogen signaling on the immune system is most often studied in terms of the nuclear estrogen receptors ERα and ERβ.

Emerging medical and engineering strategies for the prevention of long-term indwelling catheter blockage.

Urinary catheters have been used on an intermittent or indwelling basis for centuries, in order to relieve urinary retention and incontinence. Nevertheless, the use of urinary catheters in the clinical setting is fraught with complication, the most common of which is the development of nosocomial urinary tract infections, known as catheter-associated urinary tract infections. Infections of this nature are not only significant owing to their high incidence rate and subsequent economic burden but also to the severe medical consecutions that result.

Development of an Infection-Responsive Fluorescent Sensor for the Early Detection of Urinary Catheter Blockage.

Formation of crystalline biofilms following infection by Proteus mirabilis can lead to encrustation and blockage of long-term indwelling catheters, with serious clinical consequences. We describe a simple sensor, placed within the catheter drainage bag, to alert of impending blockage via a urinary color change. The pH-responsive sensor is a dual-layered polymeric "lozenge", able to release the self-quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated by the expression of bacterial urease.

Innate Sex Bias of Skin Infection Is Driven by α-Hemolysin.

Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.

The R-Enantiomer of Ketorolac Delays Mammary Tumor Development in Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) Mice.

Epidemiologic studies report improved breast cancer survival in women who receive ketorolac (Toradol) for postoperative pain relief compared with other analgesic agents. Ketorolac is a racemic drug. The S-enantiomer inhibits cyclooxygenases; R-ketorolac is a selective inhibitor of the small GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), which are signaling molecules up-regulated during breast cancer progression and metastasis.

Prevention of encrustation and blockage of urinary catheters by Proteus mirabilis via pH-triggered release of bacteriophage.

The crystalline biofilms of Proteus mirabilis can seriously complicate the care of patients undergoing long-term indwelling urinary catheterisation. Expression of bacterial urease causes a significant increase in urinary pH, leading to the supersaturation and precipitation of struvite and apatite crystals. These crystals become lodged within the biofilm, resulting in the blockage of urine flow through the catheter.

Recent advances in therapeutic delivery systems of bacteriophage and bacteriophage-encoded endolysins.

Antibiotics have been the cornerstone of clinical management of bacterial infection since their discovery in the early 20th century. However, their widespread and often indiscriminate use has now led to reports of multidrug resistance becoming globally commonplace. Bacteriophage therapy has undergone a recent revival in battle against pathogenic bacteria, as the self-replicating and co-evolutionary features of these predatory virions offer several advantages over conventional therapeutic agents.