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SELEX-HTCFQ Platform: Developing DNA Enhancers of ADAR1 to Suppress ZBP1-Dependent Immunopathology.

Excessive immune activation drives pathological inflammation through dysregulated ZBP1 signaling, yet this sensor remains crucial for immune surveillance, necessitating targeted therapies that selectively inhibit pathology, while preserving protective functions. Here, we developed an innovative SELEX-HTCFQ platform that combines the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) with high-throughput competitive fluorescence quenching (HTCFQ) to identify ADAR1-specific enhancers. Capitalizing on ADAR1's natural ability to suppress ZBP1 via competitive Z-nucleic acid binding,

Regulation of toll-like receptor signaling pathways in age-related eye disease: from mechanisms to targeted therapeutics.

Aging is a significant risk factor for various ophthalmic diseases, which can lead to vision loss. With the worldwide elderly population expanding, it is essential for researchers to elucidate the mechanisms underlying the progression of ocular diseases and to ascertain methods for their prevention or deceleration. The five principal age-related eye disorders (AREDs) consist of glaucoma, dry eye syndrome (DES), diabetic retinopathy (DR), cataracts, and age-related macular degeneration (AMD). A sustained subclinical low-grade inflammation has been observed at the ocular surface of elderly indiv

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Tra

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… Clinical studies have also revealed that ligustrazine effectively decreased peripheral blood levels of IL-8 and TNF-α in patients undergoing extracorporeal circulation, potentially contributing to the management of systemic inflammatory response syndrome during extracorporeal circulation ( Lu et al., …

Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine.

The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention o

COVID-19-Related Incidental Pancreatitis Detected on FDG-PET Scan.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) infection predominantly affects the respiratory system, it has also been found to be responsible for several gastrointestinal effects due to its capability to attack angiotensin-converting enzyme (ACE) type 2 cells in various parts of the body. Several cases of radiologically confirmed thyroiditis, axillary lymphangitis, and acute pancreatitis related to COVID-19 infection have been reported, which seem to arise from a direct cytotoxic effect of the virus itself. This case report presents

SARS-CoV-2, Cardiovascular Diseases, and Noncoding RNAs: A Connected Triad.

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by important respiratory impairments frequently associated with severe cardiovascular damages. Moreover, patients with pre-existing comorbidity for cardiovascular diseases (CVD) often present a dramatic increase in inflammatory cytokines release, which increases the severity and adverse outcomes of the infection and, finally, mortality risk. Despite this evident association at the clinical level, the mechanisms linking CVD and COVID-19 are still blurry and unresolve

PDE4 inhibition as a therapeutic strategy for improvement of pulmonary dysfunctions in Covid-19 and cigarette smoking.

Angiotensin-converting enzyme 2 (ACE2) is the binding-site and entry-point for SARS-CoV-2 in human and highly expressed in the lung. Cigarette smoking (CS) is the leading cause of pulmonary and cardiovascular diseases. Chronic CS leads to upregulation of bronchial ACE2 inducing a high vulnerability in COVID-19 smoker patients. Interestingly, CS-induced dysregulation of pulmonary renin-angiotensin system (RAS) in part contributing into the potential pathogenesis COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). Since, CS-mediated ACE2 activations is not the main pathway for inc

Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation.

Sinusoidal obstruction syndrome (SOS), previously known as hepatic veno-occlusive disease (VOD), remains a multi-organ system complication following haematopoietic cell transplantation (HCT). When SOS/VOD is accompanied by multi-organ dysfunction, overall mortality rates remain >80%. However, the definitions related to the diagnosis and grading of SOS/VOD after HCT are almost 25 years old and require new and contemporary modifications. Importantly, the pathophysiology of SOS/VOD, including the contribution of dysregulated inflammatory and coagulation cascades as well as the critical importance

Amniotic fluid embolism: moving diagnosis through the time. From the mechanical pulmonary vascular occlusion until an immuno - inflammatory pathogenesis?

Amniotic fluid embolism (AFE) is a rare, catastrophic syndrome that presents during labor and delivery or immediately postpartum. Efforts to develop a clinical diagnostic test are ongoing; however the diagnosis still relies on rapid bedside evaluation and depends on the exclusion of other diseases. Classically, the diagnosis was made at autopsy, with the demonstration of squamous cells or debris in the maternal pulmonary vasculature. Clinico-pathological correlations have strengthened the evidence for a role of the immune system in the pathogenesis of AFE and have lead to the development of ne

Contemporary treatment options for chronic prostatitis/chronic pelvic pain syndrome.

The prostate gland, about the size a walnut, forms part of the male reproductive system and sits directly underneath the bladder surrounding the urethra. It is a fibromuscular exocrine gland that secretes a complex proteolytic fluid which constitutes one-third of the volume of the seminal fluid. Prostatitis refers to a group of disorders that affect the prostate and cause genitourinary pain, dysuria, urinary frequency and sexual dysfunction. The prevalence of prostatitis in the United States has been estimated to be around 9%, while the worldwide prevalence ranges from 2 to 10%, and 15% of men

Seroprevalence of antibodies to HTLV-I in patients with ocular disorders.

Human T-lymphotropic virus type 1 (HTLV-I) has been shown to spread worldwide and to be responsible for distinct systemic diseases, namely adult T-cell leukaemia and HTLV-I-associated myelopathy. Immune-mediated, inflammatory lesions in the lungs, joints, and lacrimal glands (Sjögren's syndrome) are also suggested to be associated with the retrovirus. We studied seroprevalence of antibodies to HTLV-I in patients with various ocular disorders who are residents of south-west Japan, one of the endemic areas of HTLV-I. Of 310 patients with ocular disease 72 (23.2%) were seropositive. This seroprev

Phenome-wide screening of GWAS data reveals the complex causal architecture of obesity.

OBJECTIVE: In the present study, we sought to identify causal relationships between obesity and other complex traits and conditions using a data-driven hypothesis-free approach that uses genetic data to infer causal associations. METHODS: We leveraged available summary-based genetic data from genome-wide association studies on 1498 phenotypes and applied the latent causal variable method (LCV) between obesity and all traits. RESULTS: We identified 110 traits causally associated with obesity. Of those, 109 were causal outcomes of obesity, while only leg pain in calves was a causal determinant

Dynamic interactions between plasma IL-1 family cytokines and central endogenous opioid neurotransmitter function in humans.

Evidence in animal models suggests IL-1 family cytokines interact with central endogenous opioid neurotransmitter systems, inducing or perpetuating pathological states such as persistent pain syndromes, depression, substance use disorders, and their comorbidity. Understanding these interactions in humans is particularly relevant to understanding pathological states wherein this neurotransmitter system is implicated (ie, persistent pain, mood disorders, substance use disorders, etc). Here, we examined relationships between IL-1β, IL-1ra, and functional measures of the endogenous opioid system i

Osteopontin as a biomarker for COVID-19 severity and multisystem inflammatory syndrome in children: A pilot study.

This study sought to evaluate the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. A retrospective analysis of 26 children (0-21 years of age) admitted to Children's Healthcare of Atlanta with a diagnosis of COVID-19 between March 17 and May 26, 2020 was undertaken. The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth c

Shear stress associated with cardiopulmonary bypass induces expression of inflammatory cytokines and necroptosis in monocytes.

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furtherm

Emerging and Re-emerging Infections in Children: COVID/ MIS-C, Zika, Ebola, Measles, Varicella, Pertussis ... Immunizations.

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the ph

MIS-C and Cardiac Conduction Abnormalities.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) has spread through the pediatric population during the coronavirus disease 2019 pandemic. Our objective for the study was to report the prevalence of conduction anomalies in MIS-C and identify predictive factors for the conduction abnormalities. METHODS: We performed a single-center retrospective cohort study of pediatric patients <21 years of age presenting with MIS-C over a 1-month period. We collected clinical outcomes, laboratory findings, and diagnostic studies, including serial electrocardiograms, in all patients with MIS

New onset severe right ventricular failure associated with COVID-19 in a young infant without previous heart disease.

We present our recent experience with a 6-month-old infant with a personal history of short bowel syndrome that presented with fever, cyanosis, and cardiogenic shock secondary to severe pulmonary hypertension and right ventricular failure without pulmonary thromboembolism. He did not present signs of toxin-mediated disease or Kawasaki disease. He was finally diagnosed with SARS-CoV-2 infection. If this presentation is confirmed in future research, the severe cardiovascular impairment in children with COVID-19 could be also attributable to the primary pulmonary infection, not only to a multisys

Cat bite: an injury not to underestimate.

Domestic cat bites are common and are often treated by simple wound care with good outcome. However, delayed presentation may lead to significant morbidity or even mortality. Twenty cases of cat bites to the hand and wrist were retrospectively reviewed between 2014 and 2018. Data included patient demographics, anatomical site of injury, microbiology results, method of treatment and surgical outcome. The subjects were 18 females and two males aged 27-86 years (mean age of 58 years). Eleven patients (Group A) were presented within 48 hours of their injury. Nine patients (Group B) presented later

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study. METHODS: Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)-a nonspeci