Listeria monocytogenes can regulate and fine-tune gene expression, to adapt to diverse stress conditions encountered during foodborne transmission. To further understand the contributions of alternative sigma (σ) factors to the regulation of L. monocytogenes gene expression, RNA-Seq was performed on L. monocytogenes strain 10403S and five isogenic mutants (four strains bearing in-frame null mutations in three out of four alternative σ factor genes, ΔCHL, ΔBHL, ΔBCL, and ΔBCH, and one strain bearing null mutations in all four genes, ΔBCHL), grown to stationary phase. Our data showed that 184, 35, 34, and 20 genes were positively regulated by σB, σL, σH, and σC (posterior probability > 0.9 and Fold Change (FC) > 5.0), respectively. Moreover, σB-dependent genes showed the highest FC (based on comparisons between the ΔCHL and the ΔBCHL strain), with 44 genes showing an FC > 100; only four σL-dependent, and no σH- or σC-dependent genes showed FC >100. While σB-regulated genes identified in this study are involved in stress-associated functions and metabolic pathways, σL appears to largely regulate genes involved in a few specific metabolic pathways, including positive regulation of operons encoding phosphoenolpyruvate (PEP)-dependent phosphotransferase systems (PTSs). Overall, our data show that (i) σB and σL directly and indirectly regulate genes involved in several energy metabolism-related functions; (ii) alternative σ factors are involved in complex regulatory networks and appear to have epistatic effects in stationary phase cells; and (iii) σB regulates multiple stress response pathways, while σL and σH positively regulate a smaller number of specific pathways.Abnormal changes of the microvasculature are reported to be key evidence of the development of several critical diseases, including cancer, progressive kidney disease, and atherosclerotic plaque. Super-resolution ultrasound imaging is an emerging technology that can identify the microvasculature noninvasively, with unprecedented spatial resolution beyond the acoustic diffraction limit. Therefore, it is a promising approach for diagnosing and monitoring the development of diseases. In this review, we introduce current super-resolution ultrasound imaging approaches and their preclinical applications on different animals and disease models. Future directions and challenges to overcome for clinical translations are also discussed.Background and objectives Angiosarcomas are uncommon and extremely aggressive malignancies derived from vascular endothelial cells. Although they can occur anywhere in the body and at any age, they are more frequently found in the skin of the head and neck regions and in the elderly. Few cases have been recorded in deep soft tissues and in parenchymal organs. Angiosarcomas of the urinary bladder are exceedingly rare. They usually arise in adult patients with a history of radiation therapy, cigarette smoking, or exposure to chemical agents (e.g., vinyl chloride). Despite multidisciplinary treatment approaches combining surgery, radiotherapy, and chemotherapy, prognosis is dismal. Materials and Methods We describe a case of a 78-year-old Caucasian man presenting with a vesical mass incidentally discovered with abdominal computerized tomography (CT). He underwent transurethral resection of the bladder (TURB), and histology was compatible with angiosarcoma. Results The patient had been a heavy smoker and his medical history included therapeutic irradiation for prostate cancer eight years previously. https://www.selleckchem.com/products/imiquimod-maleate.html Radical cystoprostatectomy was feasible, and pathologic examination of the surgical specimen confirmed angiosarcoma involving the urinary bladder, prostate, and seminal vesicles. Post-operative peritonitis resulted in progressive multi-organ failure and death. Conclusions Angiosarcoma primary to the urinary bladder is seldom encountered, however, it should be considered in the differential diagnosis of vesical tumors, especially in elderly men with a history of pelvic radiotherapy.Cellular protein kinases remain the target of choice when the intention is to intervene in a particular signaling pathway leading to cancer progression [...].The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions.Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker's yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo.
Listeria monocytogenes can regulate and fine-tune gene expression, to adapt to diverse stress conditions encountered during foodborne transmission. To further understand the contributions of alternative sigma (σ) factors to the regulation of L. monocytogenes gene expression, RNA-Seq was performed on L. monocytogenes strain 10403S and five isogenic mutants (four strains bearing in-frame null mutations in three out of four alternative σ factor genes, ΔCHL, ΔBHL, ΔBCL, and ΔBCH, and one strain bearing null mutations in all four genes, ΔBCHL), grown to stationary phase. Our data showed that 184, 35, 34, and 20 genes were positively regulated by σB, σL, σH, and σC (posterior probability > 0.9 and Fold Change (FC) > 5.0), respectively. Moreover, σB-dependent genes showed the highest FC (based on comparisons between the ΔCHL and the ΔBCHL strain), with 44 genes showing an FC > 100; only four σL-dependent, and no σH- or σC-dependent genes showed FC >100. While σB-regulated genes identified in this study are involved in stress-associated functions and metabolic pathways, σL appears to largely regulate genes involved in a few specific metabolic pathways, including positive regulation of operons encoding phosphoenolpyruvate (PEP)-dependent phosphotransferase systems (PTSs). Overall, our data show that (i) σB and σL directly and indirectly regulate genes involved in several energy metabolism-related functions; (ii) alternative σ factors are involved in complex regulatory networks and appear to have epistatic effects in stationary phase cells; and (iii) σB regulates multiple stress response pathways, while σL and σH positively regulate a smaller number of specific pathways.Abnormal changes of the microvasculature are reported to be key evidence of the development of several critical diseases, including cancer, progressive kidney disease, and atherosclerotic plaque. Super-resolution ultrasound imaging is an emerging technology that can identify the microvasculature noninvasively, with unprecedented spatial resolution beyond the acoustic diffraction limit. Therefore, it is a promising approach for diagnosing and monitoring the development of diseases. In this review, we introduce current super-resolution ultrasound imaging approaches and their preclinical applications on different animals and disease models. Future directions and challenges to overcome for clinical translations are also discussed.Background and objectives Angiosarcomas are uncommon and extremely aggressive malignancies derived from vascular endothelial cells. Although they can occur anywhere in the body and at any age, they are more frequently found in the skin of the head and neck regions and in the elderly. Few cases have been recorded in deep soft tissues and in parenchymal organs. Angiosarcomas of the urinary bladder are exceedingly rare. They usually arise in adult patients with a history of radiation therapy, cigarette smoking, or exposure to chemical agents (e.g., vinyl chloride). Despite multidisciplinary treatment approaches combining surgery, radiotherapy, and chemotherapy, prognosis is dismal. Materials and Methods We describe a case of a 78-year-old Caucasian man presenting with a vesical mass incidentally discovered with abdominal computerized tomography (CT). He underwent transurethral resection of the bladder (TURB), and histology was compatible with angiosarcoma. Results The patient had been a heavy smoker and his medical history included therapeutic irradiation for prostate cancer eight years previously. https://www.selleckchem.com/products/imiquimod-maleate.html Radical cystoprostatectomy was feasible, and pathologic examination of the surgical specimen confirmed angiosarcoma involving the urinary bladder, prostate, and seminal vesicles. Post-operative peritonitis resulted in progressive multi-organ failure and death. Conclusions Angiosarcoma primary to the urinary bladder is seldom encountered, however, it should be considered in the differential diagnosis of vesical tumors, especially in elderly men with a history of pelvic radiotherapy.Cellular protein kinases remain the target of choice when the intention is to intervene in a particular signaling pathway leading to cancer progression [...].The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions.Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker's yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo.
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