Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression.

Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention.

Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death.

Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.

A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration.

Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the family and genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies.

siRNA lipid nanoparticles for CXCL12 silencing modulate brain immune response during Zika infection.

CXCL12 is a key chemokine implicated in neuroinflammation, particularly during Zika virus (ZIKV) infection. Specifically, CXCL12 is upregulated in circulating cells of ZIKV infected patients. Here, we developed a lipid nanoparticle (LNP) to deliver siRNA in vivo to assess the impact of CXCL12 silencing in the context of ZIKV infection.

Delivery of Plasmid DNA by Ionizable Lipid Nanoparticles to Induce CAR Expression in T Cells.

Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR.

Depression and loneliness symptoms in Brazilian older people during the COVID-19 pandemic: a network approach.

Objectives: Depression and loneliness in older people were a global challenge during the COVID-19 pandemic. Causal mechanisms to trigger depression might vary across different life events. We aimed to apply network analysis in a sample of Brazilian older people during the first wave of the COVID-19 pandemic, to investigate if loneliness and depression symptoms were connected within a psychological network.

HS in periodontal immuneinflammatory response and bone loss: a study in rats.

Halitosis is highly prevalent in periodontitis and attributed mainly to the presence of volatile sulfur compounds (VSC), where hydrogen sulfide (H2S) is the chief culprit in the characteristic malodor of periodontitis and thus may play an active role in its pathogenesis. The aim of this study was to evaluate the effect of H2S in the acute, intermediate and chronic immuneinflammatory host response and alveolar bone loss in vivo by using an animal model of induced periodontal disease. Thirtysix rats were divided into 2 groups: test group (n = 18), rats exposed to H2S (NaHS H2S donor molecule) and control group (n = 18), rats treated with saline only (Ctrl).

Hydrogen sulfide inhibits apoptosis and protects the bronchial epithelium in an allergic inflammation mice model.

Studies suggest that hydrogen sulfide (HS) plays a relevant and beneficial role in the pathophysiology of pulmonary allergic diseases, such as asthma. These diseases may be triggered by changes in airway epithelium caused by repeated exposure to environmental allergens. This study aimed to investigate whether HS protects against bronchial epithelium apoptosis in allergic inflammation in mice.

Treatment of chikungunya musculoskeletal disorders: a systematic review.

Chikungunya virus is amongst the fastest expanding vector transmissible diseases in recent years and has been causing massive epidemics in Africa, Asia, Latin America and the Caribbean. Despite human infection by this virus being first described in the 1950s, there is a lack of adequate therapeutic evaluations to guide evidence-based recommendations. The current guidelines rely heavily in specialists' opinion and experience instead of using higher rated evidence.

Cross-talking between lymphocytes and platelets and its regulation by nitric oxide and peroxynitrite in physiological condition and endotoxemia.

Aims: Cross-talk between platelets and lymphocytes may play a role in different pathological conditions like sepsis. This study aimed to investigate the effect of lymphocytes on platelet aggregation in lipopolysaccharide (LPS)-stimulated and non-stimulated cells.

Main Methods: Lymphocytes and platelet-rich plasma (PRP) were obtained from rat arterial blood.

Increased glutathione levels contribute to the beneficial effects of hydrogen sulfide and inducible nitric oxide inhibition in allergic lung inflammation.

Objective: The interaction between nitric oxide (NO) and hydrogen sulfide (H2S) in the airways could have significant implications for the pathogenesis and therapeutic effects of both on lung diseases. In this study we investigated whether the beneficial effects of H2S on asthma could be comparable to that inhibition of inducible NO synthase (iNOS).

Methods: Female BALB/C mice sensitized with ovalbumin (OVA) received either the H2S donor sodium hydrosulfide (NaHS, 14μmol/kg) or the iNOS inhibitor 1400W (1mg/kg), 30min before each OVA challenge during six days.

Acute and Chronic Effects of Tantric Yoga Practice on Distress Index.

Objectives: To evaluate the acute and chronic effects of yoga practice.

Design: Quantitative study using a one-group pre-posttest design.

Setting: Visão Futuro Institute, Porangaba, São Paulo, Brazil.

Early postnatal, but not late, exposure to chemical ambient pollutant 1,2-naphthoquinone increases susceptibility to pulmonary allergic inflammation at adulthood.

High diesel exhaust particle levels are associated with increased health effects; however, knowledge on the impact of its chemical contaminant 1,2-naphthoquinone (1,2-NQ) is limited. We investigated whether postnatal and adult exposures to 1,2-NQ influence allergic reaction and the roles of innate and adaptive immunity. Male neonate (6 days) and adult (56 days) C57Bl/6 mice were exposed to 1,2-NQ (100 nM; 15 min) for 3 days, and on day 59, they were sensitized and later challenged with ovalbumin (OVA).

[Cross-cultural adaptation of an instrument to evaluate older people's involvement in pleasant activities].

The sense of pleasure that arises from engagement in activities is a fundamental factor for wellbeing in the elderly. Brazil lacks an instrument to evaluate older people's involvement in pleasant activities. An American instrument was located in the international literature (The California Older Person's Pleasant Events Schedule - COPPES), evaluating the frequency with which older people engage in pleasant activities and the degree of pleasure they associate with each activity.

A comparative study on the anti-inflammatory effects of single oral doses of naproxen and its hydrogen sulfide (H2S)-releasing derivative ATB-346 in rats with carrageenan-induced synovitis.

Background: Non-steroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed agents for arthritic patients, although gastric effects limit their long-term use. Considering the reported gastric safety of hydrogen sulfide (H2S)-releasing NSAIDs, in addition to the anti-inflammatory effects of H2S administration to rats with synovitis, we decided to evaluate the effects of the H2S-releasing naproxen derivative ATB-346 in this animal model.

Methods: Male Wistar rats were anesthetized with inhalatory halothane and pre-treated with equimolar oral doses of either naproxen (0.

Hydrogen sulfide inhibits oxidative stress in lungs from allergic mice in vivo.

Recent studies show that endogenous hydrogen sulfide (H(2)S) plays an anti-inflammatory role in the pathogenesis of airway inflammation. This study investigated whether exogenous H(2)S may counteract oxidative stress-mediated lung damage in allergic mice. Female BALB/c mice previously sensitized with ovalbumin (OVA) were treated with sodium hydrosulfide (NaHS) 30 min before OVA challenge.

A systematic review of mercury ototoxicity.

Mercury is neurotoxic, and numerous studies have confirmed its ototoxic effect. However, the diagnosis and follow-up of mercury exposure require understanding the pathophysiology of the chemical substance. Based on a systematic literature review, this study aimed to demonstrate whether mercury is ototoxic and to analyze its mechanism of action on the peripheral and central auditory system, in order to contribute to the diagnosis and follow-up of exposure.

Role of the Mac-1 and VLA-4 integrins, and concomitant Th2-cytokine production, in nitric oxide modulated eosinophil migration from bone marrow to lungs in allergic mice.

Although numerous studies demonstrate the participation of nitric oxide (NO) in various inflammatory diseases, the precise function of NO in allergic asthma remains unclear. We investigated whether iNOS inhibition could interfere with the kinetics of VLA-4 and Mac-1 expression and adhesion properties of bone marrow and peripheral blood eosinophils of sensitized mice after antigen exposure. Treatment of allergic mice with 1400 W (iNOS inhibitor) increased the adhesion of bone marrow eosinophils to ICAM-1, but not blood eosinophils, at 24h and 48 h after OVA-challenge.

Knowledge, attitude and practice of breast self-examination in a female population of metropolitan São Paulo.

Objective: Evaluation of the knowledge, attitude and practice of breast self-examination in different groups of women in São Paulo.

Methods: Application of a questionnaire to 392 women divided in four groups. Group one: 101 patients of the National Health Service, Group two: 95 female physicians; Group three: 95 female medical students; and Group four: 101 wives of gynecologists.

Interactions between eotaxin and interleukin-5 in the chemotaxis of primed and non-primed human eosinophils.

This study was designed to understand the relationship between interleukin-5 and eotaxin in modulating the chemotaxis of eosinophils obtained from healthy subjects and subjects with allergic rhinitis. Chemotaxis of eosinophils from patients with allergic rhinitis toward interleukin-5 (0.25 ng/ml) was 78% higher than that of healthy subjects.

Expressions of the VLA-4, LFA-1 and Mac-1 integrins in eosinophil migration in a case of chronic eosinophilic leukaemia.

Migration of eosinophil (Eo) into tissues is a hallmark of chronic eosinophilic leukaemia (CEL), but the exact mechanism involved in cell migration is unknown. We report on a patient with CEL who presented high expressions of VLA-4, LFA-1 and Mac-1 integrins on the Eo surface, increased chemotaxis of Eo to eotaxin, decreased chemotaxis of Eo after inhibition of the cyclic guanosine monophosphate (cGMP), and a high level of intracellular cGMP. These findings suggest that an upregulation of expression of these integrins on Eo surface and a high intracellular level of cGMP may be involved in the increased Eo migration observed in our CEL patient.

Modulation of eosinophil migration from bone marrow to lungs of allergic rats by nitric oxide.

Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to peripheral blood and/or to lung. Male Wistar rats were treated with N(omega)-nitro-l-arginine methyl ester (l-NAME; 20mg/rat per day) for 4 weeks and sensitized with ovalbumin (OVA).

Nitric oxide has a role in regulating VLA-4-integrin expression on the human neutrophil cell surface.

Recent research demonstrates that the beta1 integrins may be involved in neutrophil migration. Here, we investigate the role of nitric oxide in the expression and function of the very late antigen-4 (VLA-4) and Mac-1 integrins on human neutrophils. Human blood neutrophils were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) and their adhesion to fibronectin (FN) and serum observed.

Expression of nitric oxide synthases and in vitro migration of eosinophils from allergic rhinitis subjects.

The expression of nitric oxide (NO) synthases and the role of the NO cyclic GMP pathway on the migration of eosinophils from untreated patients with allergic rhinitis were investigated. Inducible NO synthase was strongly expressed in eosinophils from healthy individuals, but not in eosinophils from allergic rhinitis patients. The neuronal isoform was observed in eosinophils from each group studied, whereas no staining for the endothelial isoform was detected in either group.