Cardiovascular and kidney diseases are positively associated with neuroinflammation and reduced brain-derived neurotrophic factor in patients with severe COVID-19.

Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms are described in many patients. However, the connection between the neuroimmune profile and the lung's inflammatory condition during COVID-19 and its association with the neurological symptoms reported by COVID-19 patients still needs further exploration. The present study characterizes the SARS-CoV-2 infectivity profile in nervous and lung tissue samples of patients who died due to severe COVID-19, and the pro-inflammatory factors present in both nervous and lung tissue samples, via a proteomic profiling array.

Oxidative Stress in the Murine Model of Extraparenchymal Neurocysticercosis.

Oxidative stress is associated with several infectious diseases, as well as the severity of inflammatory reactions. The control of inflammation during parasite destruction is a target of neurocysticercosis treatment, as inflammation is strongly related to symptom severity. In this study, we investigated the presence of malondialdehyde and protein carbonyl, two by-products of reactive oxygen species (ROS), in an experimental model of extraparenchymal neurocysticercosis.

Murine Extraparenchymal Neurocysticercosis: Appropriate Model for Evaluating Anthelminthic and Anti-Inflammatory Treatment Schedules.

Background: Experimental models of neurocysticercosis (NCC) are helpful for an improved understanding of the pathophysiological mechanisms of human diseases and for testing novel therapeutic approaches. Controlling inflammation without reducing the effectiveness of anthelmintics is an important challenge in treating neurocysticercosis. This study investigates the effects of currently used drugs (Albendazole and Dexamethasone) in treating murine extraparenchymal NCC.

Dendritic cell-based immunotherapy in non-small cell lung cancer: a comprehensive critical review.

Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg).

A mimetic peptide of ACE2 protects against SARS-CoV-2 infection and decreases pulmonary inflammation related to COVID-19.

Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro.

Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19.

COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation.

Enoxaparin improves COVID-19 by reducing Neutrophils Extracellular Traps (NETs) production.

Background: COVID-19 causes consequences such as imbalance of the immune system and thrombotic events. During the infection process, NETs in excess induce a pro-inflammatory response and disseminated intravascular coagulation. We evaluated the role of enoxaparin as a potential inhibitor of NETs.

A methanolic extract of Eclipta prostrata (L.) L. decreases inflammation in a murine model of chronic allergic asthma via inhibition of the NF-kappa-B pathway.

Ethnopharmacological Relevance: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals.

Sexual dimorphism in the murine model of extraparenchymal neurocysticercosis.

Neurocysticercosis is a heterogeneous disease, and the patient's sex seems to play a role in this heterogeneity. Hosts' sexual dimorphism in cysticercosis has been largely explored in the murine model of intraperitoneal Taenia crassiceps cysticercosis. In this study, we investigated the sexual dimorphism of inflammatory responses in a rat model of extraparenchymal neurocysticercosis caused by T.

Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury.

Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury, viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here, we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses.

The myocardial capillary network is altered in congenital diaphragmatic hernia in the fetal rabbit model.

Congenital diaphragmatic hernia (CDH) is associated with thoracic compression of the lungs and heart caused by the herniated abdominal content, leading to cardiac modifications including pressure and vascular changes. Our aim was to investigate the experimental immunoexpression of the capillary proliferation, activation, and density of Ki-67, VEGFR2, and lectin in the myocardium after surgical creation of a diaphragmatic defect. Pregnant New Zealand rabbits were operated on the 25th gestational day in order to create left-sided CDH (LCDH, n=9), right-sided CDH (RCDH, n=9), and Control (n=9), for a total of 27 fetuses in 19 pregnant rabbits.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

Background: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters.

Methods And Results: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T.

C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps.

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions and plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill patients with COVID-19 compared with patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2.

Congenital diaphragmatic hernia increases the sensitivity of pulmonary arteries to nitric oxide.

Left congenital diaphragmatic hernia (CDH) can lead to pulmonary arteries abnormalities in the contralateral and ipsilateral sides of the diaphragm. Nitric oxide (NO) is the main therapy used to attenuate the vascular effects of CDH, but it is not always effective. We hypothesized that the left and right pulmonary arteries do not respond similarly to NO donors during CDH.

The role of , and 1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.

To investigate whether interindividual variability in the (*2 and *3 alleles) and (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index.

Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model.

Background: COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment.

Gasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection.

Intracellular parasites from the Leishmania genus cause Leishmaniasis, a disease affecting millions of people worldwide. NLRP3 inflammasome is key for disease outcome, but the molecular mechanisms upstream of the inflammasome activation are still unclear. Here, we demonstrate that despite the absence of pyroptosis, Gasdermin-D (GSDMD) is active at the early stages of Leishmania infection in macrophages, allowing transient cell permeabilization, potassium efflux, and NLRP3 inflammasome activation.

CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates severe COVID-19. Here, we report that SARS-CoV-2 induces upregulation and activation of human caspase-4/CASP4 (mouse caspase-11/CASP11), and this process contributes to NLRP3 activation. In vivo infections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11-/- mice were protected from disease development, with the increased pulmonary parenchymal area, reduced clinical score of the disease, and reduced mortality.

SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner.

Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage.

Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces mild or asymptomatic COVID-19 in most cases, but some patients develop an excessive inflammatory process that can be fatal. As the NLRP3 inflammasome and additional inflammasomes are implicated in disease aggravation, drug repositioning to target inflammasomes emerges as a strategy to treat COVID-19. Here, we performed a high-throughput screening using a 2560 small-molecule compound library and identified FDA-approved drugs that function as pan-inflammasome inhibitors.

Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice.

The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising results on inhibition versus the toxic effect on A549-hACE2 cells (IC 0.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain.