SARS-CoV-2 and Systemic Lupus Erythematosus.

Purpose Of Review: To summarize current knowledge of the impact of coronavirus disease 19 (COVID-19) on patients with systemic lupus erythematosus (SLE).

Recent Findings: Several observational studies, including case series, patient surveys, and patient registries, have examined the incidence and severity of COVID-19 in patients with SLE. Due to methodologic limitations (focus on sicker patients, exclusion of asymptomatic or mild cases, limited or inaccurate viral testing), it is difficult to determine the risk and outcomes of COVID-19 in SLE patients.

Cerebrospinal Fluid Sulfonylurea Receptor-1 is Associated with Intracranial Pressure and Outcome after Pediatric TBI: An Exploratory Analysis of the Cool Kids Trial.

Sulfonylurea receptor-1 (SUR1) is recognized increasingly as a key contributor to cerebral edema, hemorrhage progression, and possibly neuronal death in multiple forms of acute brain injury. SUR1 inhibition may be protective and is actively undergoing evaluation in Phase-2/3 trials of traumatic brain injury (TBI) and stroke. In adult TBI, SUR1 expression is associated with intracranial hypertension and contusion expansion; its role in pediatric TBI remains unexplored.

Hippocampal and Prefrontal Cortical Brain Tissue Levels of Irisin and GDF15 Receptor Subunits in Children.

Cold-stress hormones (CSHs) stimulate thermogenesis and have direct neuroprotective effects on the brain. The obligatory receptor components of two new CSHs (irisin and growth differentiation factor-15 [GDF15]) were recently discovered. Irisin binds integrin-αV/β5 heterodimers while GDF-15 binds to the orphan receptor glial cell-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL).

Sirtuins play critical and diverse roles in acute kidney injury.

Acute kidney injury (AKI) is an extremely common medical affliction affecting both adult and pediatric patients resulting from hypoxic, nephrotoxic, and septic insults affecting approximately 20% of all hospital patients and up to 50% of patients in the intensive care unit. There are currently no therapeutics for patients who suffer AKI. Much recent work has focused on designing and implementing therapeutics for AKI.

A novel ultrasound-guided mouse model of sudden cardiac arrest.

Aim: Mouse models of sudden cardiac arrest are limited by challenges with surgical technique and obtaining reliable venous access. To overcome this limitation, we sought to develop a simplified method in the mouse that uses ultrasound-guided injection of potassium chloride directly into the heart.

Methods: Potassium chloride was delivered directly into the left ventricular cavity under ultrasound guidance in intubated mice, resulting in immediate asystole.

Multifaceted Benefit of Whole Blood Versus Lactated Ringer's Resuscitation After Traumatic Brain Injury and Hemorrhagic Shock in Mice.

Background: Despite increasing use in hemorrhagic shock (HS), whole blood (WB) resuscitation for polytrauma with traumatic brain injury (TBI) is largely unexplored. Current TBI guidelines recommend crystalloid for prehospital resuscitation. Although WB outperforms lactated Ringer's (LR) in increasing mean arterial pressure (MAP) in TBI + HS models, effects on brain tissue oxygenation (PbtO), and optimal MAP remain undefined.

Cardiac MRI Assessment of Mouse Myocardial Infarction and Regeneration.

Small animal models are indispensable for cardiac regeneration research. Studies in mouse and rat models have provided important insights into the etiology and mechanisms of cardiovascular diseases and accelerated the development of therapeutic strategies. It is vitally important to be able to evaluate the therapeutic efficacy and have reliable surrogate markers for therapeutic development for cardiac regeneration research.

Long noncoding RNA functionality in imprinted domain regulation.

Genomic imprinting is a parent-of-origin dependent phenomenon that restricts transcription to predominantly one parental allele. Since the discovery of the first long noncoding RNA (lncRNA), which notably was an imprinted lncRNA, a body of knowledge has demonstrated pivotal roles for imprinted lncRNAs in regulating parental-specific expression of neighboring imprinted genes. In this Review, we will discuss the multiple functionalities attributed to lncRNAs and how they regulate imprinted gene expression.

Identification of Novel Targets of RBM5 in the Healthy and Injured Brain.

The tumor suppressor RNA-binding motif 5 (RBM5) regulates the expression levels and cassette exon-definition (i.e. splicing) of a select set of mRNAs in a tissue-specific manner.

Sequential analysis of transcript expression patterns improves survival prediction in multiple cancers.

Background: Long-term survival in numerous cancers often correlates with specific whole transcriptome profiles or the expression patterns of smaller numbers of transcripts. In some instances, these are better predictors of survival than are standard classification methods such as clinical stage or hormone receptor status in breast cancer. Here, we have used the method of "t-distributed stochastic neighbor embedding" (t-SNE) to show that, collectively, the expression patterns of small numbers of functionally-related transcripts from fifteen cancer pathways correlate with long-term survival in the vast majority of tumor types from The Cancer Genome Atlas (TCGA).

Deletion of hypoxia-responsive microRNA-210 results in a sex-specific decrease in nephron number.

Low nephron number results in an increased risk of developing hypertension and chronic kidney disease. Intrauterine growth restriction is associated with a nephron deficit in humans, and is commonly caused by placental insufficiency, which results in fetal hypoxia. The underlying mechanisms by which hypoxia impacts kidney development are poorly understood.

Cerebral Edema in Traumatic Brain Injury: a Historical Framework for Current Therapy.

Purpose Of Review: The purposes of this narrative review are to (1) summarize a contemporary view of cerebral edema pathophysiology, (2) present a synopsis of current management strategies in the context of their historical roots (many of which date back multiple centuries), and (3) discuss contributions of key molecular pathways to overlapping edema endophenotypes. This may facilitate identification of important therapeutic targets.

Recent Findings: Cerebral edema and resultant intracranial hypertension are major contributors to morbidity and mortality following traumatic brain injury.

Lamin B2 Levels Regulate Polyploidization of Cardiomyocyte Nuclei and Myocardial Regeneration.

Heart regeneration requires cardiomyocyte proliferation. It is thought that formation of polyploid nuclei establishes a barrier for cardiomyocyte proliferation, but the mechanisms are largely unknown. Here, we show that the nuclear lamina filament Lamin B2 (Lmnb2), whose expression decreases in mice after birth, is essential for nuclear envelope breakdown prior to progression to metaphase and subsequent division.

Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death.

Ferroptotic death is the penalty for losing control over three processes-iron metabolism, lipid peroxidation and thiol regulation-that are common in the pro-inflammatory environment where professional phagocytes fulfill their functions and yet survive. We hypothesized that redox reprogramming of 15-lipoxygenase (15-LOX) during the generation of pro-ferroptotic signal 15-hydroperoxy-eicosa-tetra-enoyl-phosphatidylethanolamine (15-HpETE-PE) modulates ferroptotic endurance. Here, we have discovered that inducible nitric oxide synthase (iNOS)/NO-enrichment of activated M1 (but not alternatively activated M2) macrophages/microglia modulates susceptibility to ferroptosis.

Increased rates of vesicoureteral reflux in mice from deletion of Dicer in the peri-Wolffian duct stroma.

Background: Vesicoureteral reflux (VUR), backflow of urine into the kidney, is associated with urinary tract infections and chronic kidney disease. Integrity of the vesicoureteral junction (VUJ), where reflux occurs, is determined largely by proper induction of the ureteric bud from the Wolffian duct. Induction is modulated by signals from the surrounding peri-Wolffian duct stroma.

Genetics of Antiphospholipid Syndrome.

Purpose Of Review: Antiphospholipid syndrome (APS) is a rare heterogenous disorder associated with the presence of antiphospholipid antibodies and can present in a wide variety of clinical manifestations including thrombosis and pregnancy complications. Although the etiology of APS remains poorly understood, there is strong support for considering APS as a complex genetic disease in which multiple genetic risk factors, in conjunction with environmental factors, affect its onset, progression, and severity. Here, we provide a comprehensive review of the current knowledge of the genetic basis of APS, which remains in its infancy.

Robust RBM3 and β-klotho expression in developing neurons in the human brain.

RNA binding motif 3 (RBM3) is a powerful neuroprotectant that inhibits neurodegenerative cell death in vivo and is a promising therapeutic target in brain ischemia. RBM3 is increased by the hormone fibroblast growth factor 21 (FGF21) in an age- and temperature-dependent manner in rat cortical neurons. FGF21 receptor binding is controlled by the transmembrane protein β-klotho, which is mostly absent in the adult brain.

In utero exposure to maternal diabetes impairs nephron progenitor differentiation.

The incidence of diabetes mellitus has significantly increased among women of childbearing age, and it has been shown that prenatal exposure to maternal diabetes increases the risk of associated congenital anomalies of the kidney. Congenital anomalies of the kidney are among the leading causes of chronic kidney disease in children. To better understand the effect of maternal diabetes on kidney development, we analyzed wild-type offspring (DM_Exp) of diabetic mice (Akita mice).

Preclinical Dosimetry, Imaging, and Targeted Radionuclide Therapy Studies of Lu-177-Labeled Albumin-Binding, PSMA-Targeted CTT1403.

Purpose: Prostate-specific membrane antigen (PSMA) continues to be the hallmark biomarker for prostate cancer as it is expressed on nearly all prostatic tumors. In addition, increased PSMA expression correlates with castration resistance and progression to the metastatic stage of the disease. Recently, we combined both an albumin-binding motif and an irreversible PSMA inhibitor to develop the novel PSMA-targeted radiotherapeutic agent, CTT1403.

Expression patterns of small numbers of transcripts from functionally-related pathways predict survival in multiple cancers.

Background: Genetic profiling of cancers for variations in copy number, structure or expression of certain genes has improved diagnosis, risk-stratification and therapeutic decision-making. However the tumor-restricted nature of these changes limits their application to certain cancer types or sub-types. Tests with broader prognostic capabilities are lacking.

Kidney-in-a-lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates.

Stem cell-derived organoids are emerging as sophisticated models for studying development and disease and as potential sources for developing organ substitutes. Unfortunately, although organoids containing renal structures have been generated from mouse and human pluripotent stem cells, there are still critical unanswered questions that are difficult to attain via in vitro systems, including whether these nonvascularized organoids have a stable and physiologically relevant phenotype or whether a suitable transplantation site for long-term in vivo studies can be identified. Even orthotopic engraftment of organoid cultures in the adult does not provide an environment conducive to vascularization and functional differentiation.