Postbiotic lactobacilli induce cutaneous antimicrobial response and restore the barrier to inhibit the intracellular invasion of Staphylococcus aureus in vitro and ex vivo.

Intracellular pathogens including Staphylococcus aureus contribute to the non-healing phenotype of chronic wounds. Lactobacilli, well known as beneficial bacteria, are also reported to modulate the immune system, yet their role in cutaneous immunity remains largely unknown. We explored the therapeutic potential of bacteria-free postbiotics, bioactive lysates of lactobacilli, to reduce intracellular S.

An Optimized and Advanced Algorithm for the Quantification of Immunohistochemical Biomarkers in Keratinocytes.

Advancements in pathology have given rise to software applications intended to minimize human error and improve efficacy of image analysis. Still, the subjectivity of image quantification performed manually and the limitations of the most ubiquitous tissue stain analysis software requiring parameters tuned by the observer, reveal the need for a highly accurate, automated nuclear quantification software specific to immunohistochemistry, with improved precision and efficiency compared with the methods currently in use. We present a method for the quantification of immunohistochemical biomarkers in keratinocyte nuclei proposed to overcome these limitations, contributing sensitive shape-focused segmentation, accurate nuclear detection, and automated device-independent color assessment, without observer-dependent analysis parameters.

Single-nucleus RNA sequencing of developing superior colliculus identifies neuronal diversity and candidate mediators of circuit assembly.

The superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during development, rendering the mouse SC a popular model to study establishment of neural connectivity. Here we perform single-nucleus RNA-sequencing analysis of the mouse SC isolated at various developmental time points.

Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly.

The superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during development, rendering the mouse SC a popular model to study establishment and refinement of neural connectivity. Here we performed single nucleus RNA-sequencing analysis of the mouse SC isolated at various developmental time points.

MicroRNA let-7 Downregulates Ligand-Independent Estrogen Receptor-mediated Male-Predominant Pulmonary Fibrosis.

The relevance of hormones in idiopathic pulmonary fibrosis (IPF), a predominantly male lung disease, is unknown. To determine whether the ER (estrogen receptor) facilitates the development of pulmonary fibrosis and is mediated in part through microRNA regulation of ERα and ERα-activated profibrotic pathways. ER expression in male lung tissue and myofibroblasts from control subjects ( = 6) and patients with IPF ( = 6), aging bleomycin (BLM)-treated mice ( = 7), and BLM-treated AF2ERKI mice ( = 7) was determined.

Estrogen receptor subtype ratio change protects against podocyte damage.

Women are relatively protected against the development and progression of glomerulosclerosis (GS) prior to menopause. However, the "female advantage" is lost in women who are either diabetic, post-menopausal or both. We showed that 17β-estradiol (E) was effective in prevention of diabetic GS development in part through the stabilization of podocyte cytoskeleton and a change in estrogen receptor (ER) subtype ratio.

Estrogen receptor subtype expression and regulation is altered in papillary thyroid cancer after menopause.

Background: Estrogen receptors can regulate growth in papillary thyroid cancer and may affect prognosis after menopause. This study examines changes of estrogen receptor subtype ratio expression in papillary thyroid cancer cell lines derived from pre- and postmenopausal women.

Methods: Cells were harvested from papillary thyroid cancer and non-papillary thyroid cancer thyroid tissue (control) from pre- (n = 9) and postmenopausal women (n = 11).

Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis.

The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced pulmonary fibrosis spontaneously resolve in young mice, whereas remaining irreversible in aged mice suggests that impairment of pulmonary regeneration and repair is associated with aging. Because mesenchymal stem cells (MSCs) may promote repair after injury, we postulated that differences in MSCs from aged mice may underlie postinjury fibrosis in aging. The potential for young-donor MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has not been studied.

Expression of Receptors for Pituitary-Type Growth Hormone-Releasing Hormone (pGHRH-R) in Human Papillary Thyroid Cancer Cells: Effects of GHRH Antagonists on Matrix Metalloproteinase-2.

Papillary thyroid cancer (PTC) is the most prevalent of all endocrine cancers. In recent studies, the presence of receptors for pituitary-type growth hormone-releasing hormone (pGHRH-R) has been demonstrated in various human cancers, including human prostate, brain, and other cancer lines. Thyroid malignancies, however, have not yet been investigated in this regard.

In vivo 17β-estradiol treatment contributes to podocyte actin stabilization in female db/db mice.

We recently showed that 17β-estradiol (E(2)) treatment ameliorated type 2 diabetic glomerulosclerosis in mice in part by protecting podocyte structure and function. Progressive podocyte damage is characterized by foot process effacement, vacuolization, detachment of podocytes from the glomerular basement membrane, and apoptosis. In addition, podocytes are highly dependent on the preservation of their actin cytoskeleton to ensure proper function and survival.

Oxidant stress and mitochondrial signaling regulate reversible changes of ERα expression and apoptosis in aging mouse glomeruli and mesangial cells.

Estrogen actions are largely dependent on the intracellular estrogen receptor (ER) levels. During aging the decline of estrogens or ER leads to a loss in antiinflammatory protection and an increase in oxidant stress due to changes in mitochondrial function. Estrogens/ER may also coordinate signaling between the nucleus and mitochondria through ERK activation, which paradoxically decreases ER expression.

Testosterone and 17β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice.

Podocyte damage and apoptosis are thought to be important if not essential in the development of glomerulosclerosis. Female estrogen receptor knockout mice develop glomerulosclerosis at 9 months of age due to excessive ovarian testosterone production and secretion. Here, we studied the pathogenesis of glomerulosclerosis in this mouse model to determine whether testosterone and/or 17β-estradiol directly affect the function and survival of podocytes.

Estrogen receptor beta protects against in vivo injury in RPE cells.

Epidemiological data suggest that estrogen deficiency in postmenopausal women may contribute to the severity of AMD. We discovered that 17beta-estradiol (E2) was a crucial regulator of the severity of extracellular matrix turnover (ECM) dysregulation both in vivo and in vitro. We also found in vitro that the presence of estrogen receptor (ER)beta regulates MMP-2 activity.

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking.

Inhibition of C-jun N-terminal kinase improves insulin sensitivity but worsens albuminuria in experimental diabetes.

C-jun N-terminal kinase (JNK) regulates both the development of insulin resistance and inflammation. Podocytes of the widely used db/db mouse model of diabetic nephropathy lose their ability to respond to insulin as albuminuria develops, in comparison to control db/+ mice. Here we tested whether JNK inhibition or its gene deletion would prevent albuminuria in experimental diabetes.

Subtype specific estrogen receptor action protects against changes in MMP-2 activation in mouse retinal pigmented epithelial cells.

Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). AMD is about two times more prevalent in aging postmenopausal women. Therefore we studied whether 17beta-estradiol (E(2)) modulates the expression and activity of the trimolecular complex (MMP-2, TIMP-2 and MMP-14), molecules which are of major importance for ECM turnover in RPE.

Activation of the estrogen receptor contributes to the progression of pulmonary lymphangioleiomyomatosis via matrix metalloproteinase-induced cell invasiveness.

Context: The role of estrogens in the pathogenesis of lymphangioleiomyomatosis (LAM), an aggressive and destructive, eventually fatal lung disease of women, is poorly understood.

Objective: The study was conducted to test the hypothesis that the lung disease in LAM is estrogen mediated and to determine whether estrogens contribute to the invasiveness of LAM.

Design: In vitro cell culture of spindle-shaped LAM cells (LAMD-SM) were isolated and propagated from affected lungs.

Bot1p is required for mitochondrial translation, respiratory function, and normal cell morphology in the fission yeast Schizosaccharomyces pombe.

Maintenance of cell morphology is essential for normal cell function. For eukaryotic cells, a growing body of recent evidence highlights a close interdependence between mitochondrial function, the cytoskeleton, and cell cycle control mechanisms; however, the molecular details of this interconnection are still not completely understood. We have identified a novel protein, Bot1p, in the fission yeast Schizosaccharomyces pombe.

Repetitive nonlethal oxidant injury to retinal pigment epithelium decreased extracellular matrix turnover in vitro and induced sub-RPE deposits in vivo.

Purpose: To determine the impact of repetitive nonlethal oxidant injury with hydroquinone (HQ) on regulation of cell membrane blebbing and molecules, which are essential in extracellular matrix turnover (ECM) maintenance, especially matrix metalloproteinase (MMP)-2, tissue inhibitor of MMP (TIMP)-2, and type IV collagen in cultured RPE. In addition, to determine whether chronic oral HQ causes induction of sub-RPE deposit formation in a mouse model.

Methods: An ARPE-19 cell line stably expressing membrane-targeted green fluorescent protein (GFP) was challenged by exposure to HQ (100 microM).