Exogenous miRNAs encourage posttranscriptional gene silencing inside crops

Myeloid derived suppressor cells (MDSCs) are a heterogeneous group of immature cells that accumulate in the peripheral blood and tumor microenvironment and are barriers to cancer therapy. MDSCs serve as prognostic biomarkers and are targets for therapy. Based on surface markers, three subsets of MDSCs have been defined in humans granulocytic, monocytic and early-stage (e-MDSCs). The markers attributed to e-MDSCs overlap with those of basophils, which are rare circulating myeloid cells with unrecognized roles in cancer. Thus, we asked whether e-MDSCs in circulation and the tumor microenvironment include basophils. On average 58% of cells with e-MDSC surface markers in blood and 36% in ascites from patients with ovarian cancer (OC) were basophils based on CD123high expression and cytology, whereas cells with immature features were rare. Circulating and ascites basophils did not suppress proliferation of stimulated T cells, a key feature of MDSCs. Increased accumulation of basophils and basogranulin, a marker of basophil degranulation, were observed in ascites compared to serum in patients with newly diagnosed OC. Basophils recruited to the tumor microenvironment may exacerbate fluid accumulation by their release of pro-inflammatory granular constituents that promote vascular leakage. No significant correlation was observed between peripheral basophil counts and survival in patients with OC. Our results suggest that studies in which e-MDSCs were defined solely by surface markers should be re-revaluated to exclude basophils. Both immaturity and suppression are criteria to define e-MDSCs in future studies. Copyright ©2020, American Association for Cancer Research.The 2018 and 2019 guidelines from the American College of Cardiology and American Heart Association reflect the complexity of individualized cholesterol management. The documents address more detailed risk assessment, newer nonstatin cholesterol-lowering drugs, special attention to patient subgroups, and consideration of the value of therapy, all with the aim of creating personalized treatment plans for each patient. Overall, the guidelines recommend shared decision-making to meet the individual needs of each patient. Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.Gastroesophageal reflux disease (GERD) is mainly a clinical diagnosis based on typical symptoms of heartburn and acid regurgitation. Current guidelines indicate that patients with typical symptoms should first try a proton pump inhibitor (PPI). If reflux symptoms persist after 8 weeks on a PPI, endoscopy of the esophagus is recommended, with biopsies taken to rule out eosinophilic esophagitis. This review discusses the evidence for different medical, endoscopic, and surgical therapies and presents a management algorithm. Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.The cornerstone of preventive migraine treatment has long been drugs developed for other diseases such as epilepsy, depression, and hypertension. But a new set of drugs is available for preventing migraine attacks erenumab, galcanezumab, fremanezumab, and eptinezumab. These monoclonal antibodies target calcitonin gene-related peptide (CGRP) or its receptors, each a key molecule in the pathophysiology of migraine. Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.Fracture is a major cause of morbidity and death in postmenopausal women. Dual-energy x-ray absorptiometry (DXA) measures bone mineral density, which helps in estimating fracture risk and in identifying those who may benefit from treatment. Although screening guidelines differ somewhat for postmenopausal women under age 65, in general, DXA is indicated if the patient has a high risk for fracture. Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we will focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology. Copyright © 2020 by the American Society of Nephrology.SUMMARYCaseum, the central necrotic material of tuberculous lesions, is a reservoir of drug-recalcitrant persisting mycobacteria. Caseum is found in closed nodules and in open cavities connecting with an airway. Several commonly accepted characteristics of caseum were established during the preantibiotic era, when autopsies of deceased tuberculosis (TB) patients were common but methodologies were limited. These pioneering studies generated concepts such as acidic pH, low oxygen tension, and paucity of nutrients being the drivers of nonreplication and persistence in caseum. Here we review widely accepted beliefs about the caseum-specific stress factors thought to trigger the shift of Mycobacterium tuberculosis to drug tolerance. Our current state of knowledge reveals that M. tuberculosis is faced with a lipid-rich diet rather than nutrient deprivation in caseum. Variable caseum pH is seen across lesions, possibly transiently acidic in young lesions but overall near neutral in most mature lesions. Oxygen tension is low in the avascular caseum of closed nodules and high at the cavity surface, and a gradient of decreasing oxygen tension likely forms toward the cavity wall. Since caseum is largely made of infected and necrotized macrophages filled with lipid droplets, the microenvironmental conditions encountered by M. tuberculosis in foamy macrophages and in caseum bear many similarities. While there remain a few knowledge gaps, these findings constitute a solid starting point to develop high-throughput drug discovery assays that combine the right balance of oxygen tension, pH, lipid abundance, and lipid species to model the profound drug tolerance of M. SHIN1 inhibitor tuberculosis in caseum. Copyright © 2020 American Society for Microbiology.