Effects of nanocapsules containing lumefantrine and artemether in an experimental model of cerebral malaria.

Background: Malaria, a tropical neglected disease, imposes a significant burden on global health, leading to the loss of thousands of lives annually. Its gold standard treatment is a combination therapy of lumefantrine (LUM) and artemether (ART). Nanotechnology holds significant potential for improving drug bioavailability and potency while reducing adverse effects.

Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process.

Background: Severe malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65).

The Na/K-ATPase role as a signal transducer in lung inflammation.

Acute respiratory distress syndrome (ARDS) is marked by damage to the capillary endothelium and alveolar epithelium following edema formation and cell infiltration. Currently, there are no effective treatments for severe ARDS. Pathologies such as sepsis, pneumonia, fat embolism, and severe trauma may cause ARDS with respiratory failure.

Beneficial effects of empagliflozin and liraglutide on the cerebral microcirculation of diabetic rats.

Objectives: This study aimed to evaluate the effects of the antidiabetics liraglutide, a GLP-1 analog, and empagliflozin, an SGLT-2 inhibitor, on the brain microcirculation of diabetic rats.

Methods: Type 2 diabetes mellitus (DM) was experimentally induced in male Wistar rats by combining a high-fat diet and a low dose of streptozotocin (35 mg/kg). Liraglutide (100 μg/kg s.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19).

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH).

Age-linked suppression of lipoxin A4 associates with cognitive deficits in mice and humans.

Age increases the risk for cognitive impairment and is the single major risk factor for Alzheimer's disease (AD), the most prevalent form of dementia in the elderly. The pathophysiological processes triggered by aging that render the brain vulnerable to dementia involve, at least in part, changes in inflammatory mediators. Here we show that lipoxin A4 (LXA4), a lipid mediator of inflammation resolution known to stimulate endocannabinoid signaling in the brain, is reduced in the aging central nervous system.

Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases.

Despite the fast development of vaccines, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still circulates through variants of concern (VoC) and escape the humoral immune response. SARS-CoV-2 has provoked over 200,000 deaths/months since its emergence and only a few antiviral drugs showed clinical benefit up to this moment. Thus, chemical structures endowed with anti-SARS-CoV-2 activity are important for continuous antiviral development and natural products represent a fruitful source of substances with biological activity.

Fluorine Atoms on CH-Corrole Affect the Interaction with M and PL Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches.

The chymotrypsin-like cysteine protease (3CL, also known as main protease-M) and papain-like protease (PL) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation of the most promising compounds. In this sense, the present work reports for the first time the evaluation of the interaction between M/PL with a series of 17 porphyrin analogues-corrole (), -aryl-corrole (), and 15 fluorinated--aryl-corrole derivatives (-) via molecular docking calculations. The impact of fluorine atoms on -aryl-corrole structure was also evaluated in terms of binding affinity and physical-chemical properties by two-dimensional quantitative structure-activity relationship (2D-QSAR).

Proteomic Profile of Procoagulant Extracellular Vesicles Reflects Complement System Activation and Platelet Hyperreactivity of Patients with Severe COVID-19.

Background: Extracellular vesicles (EVs) are a valuable source of biomarkers and display the pathophysiological status of various diseases. In COVID-19, EVs have been explored in several studies for their ability to reflect molecular changes caused by SARS-CoV-2. Here we provide insights into the roles of EVs in pathological processes associated with the progression and severity of COVID-19.

Commercially Available Flavonols Are Better SARS-CoV-2 Inhibitors than Isoflavone and Flavones.

Despite the fast development of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still circulating and generating variants of concern (VoC) that escape the humoral immune response. In this context, the search for anti-SARS-CoV-2 compounds is still essential. A class of natural polyphenols known as flavonoids, frequently available in fruits and vegetables, is widely explored in the treatment of different diseases and used as a scaffold for the design of novel drugs.

Clinical features, electroencephalogram, and biomarkers in pediatric sepsis-associated encephalopathy.

To date, no specific diagnostic criteria for sepsis-associated encephalopathy (SAE) have been established. We studied 33 pediatric patients with sepsis prospectively and evaluated the level of consciousness, the presence of delirium, electroencephalographic (EEG) findings, and plasma levels of neuron-specific enolase and S100-calcium-binding protein-B. A presumptive diagnosis of SAE was primarily considered in the presence of a decreased level of consciousness and/or delirium (clinical criteria), but specific EEG abnormalities were also considered (EEG criteria).

Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a significant threat to critically ill patients with a high fatality rate. Pollutant exposure, cigarette smoke, infectious agents, and fatty acids can induce ARDS. Animal models can mimic the complex pathomechanism of the ARDS.

SARS-CoV-2 Infection and Possible Neonatal Neurological Outcomes: A Literature Review.

The virus responsible for COVID-19 is designated "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), a highly transmissible and pathogenic coronavirus. Although people of all ages are susceptible to SARS-CoV-2 infection, clinical manifestations may vary with age. The response of neonates to SARS-CoV-2 infection or exposure differs from that of children and adults.

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP).

TLR4 mutation protects neurovascular function and cognitive decline in high-fat diet-fed mice.

Background: Metabolic syndrome (MS) is defined as a low-grade proinflammatory state in which abnormal metabolic and cardiovascular factors increase the risk of developing cardiovascular disease and neuroinflammation. Events, such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in MS may contribute to the direct or indirect activation of Toll-like receptors (TLRs), specifically TLR4, which is thought to be a major component of this syndrome. Activation of the innate immune response via TLR4 may contribute to this state of chronic inflammation and may be related to the neuroinflammation and neurodegeneration observed in MS.

Systemic Response to Infection Induces Long-Term Cognitive Decline: Neuroinflammation and Oxidative Stress as Therapeutical Targets.

In response to pathogens or damage signs, the immune system is activated in order to eliminate the noxious stimuli. The inflammatory response to infectious diseases induces systemic events, including cytokine storm phenomenon, vascular dysfunction, and coagulopathy, that can lead to multiple-organ dysfunction. The central nervous system (CNS) is one of the major organs affected, and symptoms such as sickness behavior (depression and fever, among others), or even delirium, can be observed due to activation of endothelial and glial cells, leading to neuroinflammation.

Atazanavir Is a Competitive Inhibitor of SARS-CoV-2 M, Impairing Variants Replication In Vitro and In Vivo.

Atazanavir (ATV) has already been considered as a potential repurposing drug to 2019 coronavirus disease (COVID-19); however, there are controversial reports on its mechanism of action and effectiveness as anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Through the pre-clinical chain of experiments: enzymatic, molecular docking, cell-based and in vivo assays, it is demonstrated here that both SARS-CoV-2 B.1 lineage and variant of concern gamma are susceptible to this antiretroviral.

Immunomodulatory and Anti-fibrotic Effects Following the Infusion of Umbilical Cord Mesenchymal Stromal Cells in a Critically Ill Patient With COVID-19 Presenting Lung Fibrosis: A Case Report.

The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation.

6-Shogaol Exerts a Neuroprotective Factor in Offspring after Maternal Immune Activation in Rats.

6-Shogaol is one of the main active phenolic components of ginger and has neuroprotective effects by protecting brain against the oxidative stress and regulate the levels of neurotrophic factors. The objective of the present study was to verify the effect of 6-shogaol on neurochemical parameters in offspring after maternal immune activation by lipopolysaccharide (LPS) in rats. Twelve pregnant Wistar rats received 100 μg/kg of LPS or saline solution on the gestational day 9.

PMA treatment fosters rat retinal ganglion cell survival via TNF signaling.

An insult can trigger a protective response or even cell death depending on different factors that include the duration and magnitude of the event and the ability of the cell to activate protective intracellular signals, including inflammatory cytokines. Our previous work showed that the treatment of Lister Hooded rat retinal cell cultures with 50 ng/mL phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, increases the survival of retinal ganglion cells (RGCs) kept in culture for 48 h after axotomy. Here we aim to analyze how PMA modulates the levels of TNF-α and IL-1β (both key inflammatory mediators) and the impact of this modulation on RGCs survival.

Neurological impairment caused by Schistosoma mansoni systemic infection exhibits early features of idiopathic neurodegenerative disease.

Schistosomiasis, a neglected tropical disease caused by trematodes of the Schistosoma genus, affects over 250 million people around the world. This disease has been associated with learning and memory deficits in children, whereas reduced attention levels, impaired work capacity, and cognitive deficits have been observed in adults. Strongly correlated with poverty and lack of basic sanitary conditions, this chronic endemic infection is common in Africa, South America, and parts of Asia and contributes to inhibition of social development and low quality of life in affected areas.