RNAscope

Hippocampal Cb2 receptors: an untold story

The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb1 receptors (Cb1Rs), Cb2 receptors (Cb2Rs) in the brain have started to attract considerable interest in recent years.

Accumulation of Aggrecan at Sites of Increased Pulmonary Arterial Pressure in Idiopathic Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a lethal condition lacking curative pharmacotherapy. Expansion of the extracellular matrix occurs in early stages of pulmonary angiopathy, but the presence of individual matrix components warrants further investigation. Accumulation of the osmotically active matrix proteoglycan aggrecan has been associated with swelling and disruption of vessel wall integrity in systemic arteries. Whether aggrecan is present to any significant extent in PAH tissue, and what potential role it may have, is not known.

928 A translational approach to catalog pancreatic cancer heterogeneity using spatial genomics in large patient cohorts for target validation and rational combination selection

BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with short overall survival; the standard of care (SoC) is chemotherapy. Immunotherapies in development aim to remodel the stroma by depleting immunosuppressive cell types or using T-cell redirection to kill tumor cells. To date, none of these methods have improved overall survival beyond SoC. Next generation immunotherapies that employ histopathology and molecular subtyping1 for target and patient selection may succeed.

Emerging Microbes & Infections - Original Article: Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany

In 2021, three encephalitis cases due to the Borna disease virus 1 (BoDV-1) were diagnosed in the north and east of Germany. The patients were from the states of Thuringia, Saxony-Anhalt, and Lower Saxony. All were residents of known endemic areas for animal Borna disease but without prior diagnosed human cases. Except for one recently detected case in the state of Brandenburg, all >30 notified cases had occurred in, or were linked to, the southern state of Bavaria.

Reduced β-catenin immunostaining in prostate cancer and negatively associated with poorly differentiated Gleason grades

Prostate cancer has few prognostic biomarkers, and differentiating between relapsing and nonrelapsing tumour can be challenging clinically. This study aims to investigate the hypothesis that β-catenin might be a potential biomarker for prostate tumour and could distinguish between aggressive tumours requiring radical intervention and those that have a good prognosis. It is thought to be a potential biomarker that can predict the clinical progression and prognosis of different kinds of tumors.

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of COVID-19 and what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome, remains poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19.

Intact prostaglandin signaling through EP2 and EP4 receptors in stromal progenitor cells is required for normal development of the renal cortex in mice

Cyclooxygenase (Cox) inhibitors are known to have severe side effects during renal development. These consist of reduced renal function, underdeveloped subcapsular glomeruli, interstitial fibrosis and thinner cortical tissue. Global genetic deletion of Cox-2 mimics the phenotype observed after application of Cox-inhibitors. This study aimed to investigate which cell-types express Cox-2 and the prostaglandin E2 receptors and what functions are mediated through this pathway during renal development.

Cassava Brown Streak Viruses express second 6-kilodalton (6K2) protein with varied polarity and three dimensional (3D) structures: Basis for trait discrepancy between the virus species

Cassava Brown Streak Virus (CBSV) and Ugandan Cassava Brown Streak Virus (UCBSV) are the two among six virus species speculated to cause the most catastrophic Brown Streak Disease of Cassava (CBSD) in Africa and Asia. For unknown reasons, Cassava Brown Streak Virus (CBSV) is hard to breed resistance for compared to Ugandan Cassava Brown Streak Virus (UCBSV) species. This exemplified by incidences of CBSV species rather than UCBSV species in elite breeding line, KBH 2006/0026 at Bagamoyo, Tanzania.

Pharmacological Manipulation of Early Zebrafish Skeletal Development Shows an Important Role for Smad9 in Control of Skeletal Progenitor Populations

Osteoporosis and other conditions associated with low bone density or quality are highly prevalent, are increasing as the population ages and with increased glucocorticoid use to treat conditions with elevated inflammation. There is an unmet need for therapeutics which can target skeletal precursors to induce osteoblast differentiation and osteogenesis. Genes associated with high bone mass represent interesting targets for manipulation, as they could offer ways to increase bone density. A damaging mutation in SMAD9 has recently been associated with high bone mass.

Esterification promotes the intracellular accumulation of roxadustat, an activator of hypoxia-inducible factors, to extend its effective duration

Kidney injury often causes anemia due to a lack of production of the erythroid growth factor erythropoietin (EPO) in the kidneys. Roxadustat is one of the first oral medicines inducing EPO production in patients with renal anemia by activating hypoxia-inducible factors (HIFs), which are activators of EPO gene expression. In this study, to develop prodrugs of roxadustat with improved permeability through cell membrane, we investigated the effects of 8 types of esterification on the pharmacokinetics and bioactivity of roxadustat using Hep3B hepatoma cells that HIF-dependently produce EPO.

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