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Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia., (© 2024 Federation of American Societies for Experimental Biology.)

Conventional views associate microbial biofilm with demineralization in root caries (RC) onset, while research on their collagenases role in the breakdown of collagen matrix has been sporadically developed, primarily in vitro. Recent discoveries, however, reveal proteolytic bacteria enrichment, specially Porphyromonas and other periodontitis-associated bacteria in subgingivally extended lesions, suggesting a potential role in RC by the catabolism of dentin organic matrix. Moreover, genes encoding proteases and bacterial collagenases, including the U32 family collagenases, were found to be overexpressed in both coronal and root dentinal caries. Despite these advancements, to prove microbial collagenolytic proteases' definitive role in RC remains a significant challenge. A more thorough investigation is warranted to explore the potential of anti-collagenolytic agents in modulating biofilm metabolic processes or inhibiting/reducing the size of RC lesions. Prospective treatments targeting collagenases and promoting biomodification through collagen fibril cross-linking show promise for RC prevention and management. However, these studies are currently in the in vitro phase, necessitating additional research to translate findings into clinical applications. This is a comprehensive state-of-the-art review aimed to explore contributing factors to the formation of RC lesions, particularly focusing on collagen degradation in root tissues by microbial collagenases.

Objective: To assess the agreement between complementary feeding indicators established by the World Health Organization (WHO) and the Ministry of Health (MOH) and to compare the prevalence of these indicators in the first year of a child's life., Methods: : This was a cross-sectional study in a cohort of 286 children from Vitória da Conquista, state of Bahia, Brazil; agreement between indicators and comparison between prevalences were analyzed using the Kappa coefficient and McNemar's test; the prevalence of the indicators "introduction of complementary feeding" (ICF), "minimum dietary diversity" (MDD), "minimum meal frequency" (MMF) and "minimum acceptable diet" (MAD) were calculated., Results: : Three indicators showed poor agreement, with only one demonstrating moderate agreement; prevalence of WHO indicators was higher than that of the MOH (ICF, 94.3% vs. 20.7%; MDD, 75.2% vs. 50.7%; MMF, 97.2% vs. 44.8%; MAD, 96.8% vs. 26.9%)., Conclusion: The majority of indicators showed poor agreement and the prevalence of WHO indicators exceeded that of the Ministry of Health.

Introduction and Aim: The presence of host collagenases in the degradation of the protein matrix at later stages of carious dentin lesions development, as well as the potential involvement of bacterial collagenases, have been suggested but lack conclusive evidence. This study aims to conduct a systematic review to comprehensively assess the profile of host and bacterial-derived collagenolytic proteases in both root and coronal dentin carious lesions., Methods: The search was performed in eight databases and the grey literature. Studies evaluating ex vivo dentin, extracted teeth, or biofilms from natural caries lesions were included. The methodological quality of studies was assessed using the Joanna Briggs Institute tool. Synthesis of the results and the certainty of evidence were performed following the Synthesis without Meta-analysis (SWiM) checklist and GRADE approach for narrative synthesis, respectively., Results: From 935 recovered articles, 18 were included. Although the evidence was very uncertain, it was possible to suggest that 1) MMP-2, MMP-9, MMP-13, and CT-B may be increased in carious dentin when compared to sound dentin; 2) there is no difference in MMP-2 presence, while MMP-13 may be increased in root when compared to coronal carious dentin; 3) there is no difference of MMP-2 and MMP-9 expression/activity before and after cavity sealing; 4) MMP-8 may be increased in the dentin before cavity sealing compared to dentin after cavity sealing; 5) there is no difference of MMP-20 in irradiated vs. non-irradiated carious dentin. MMP-20 probably reduces in carious outer dentin when compared to carious inner dentin (moderate certainty). Genes encoding bacterial collagenolytic proteases and protein-degrading bacteria were detected in coronal and root carious lesions., Conclusion: Trends in the direction of the effect were observed for some collagenolytic proteases in carious dentin, which may represent a potential target for the development of new treatments. (Protocol register-PROSPERO: CRD42020213141)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Barbosa, Monici Silva, Cena, Stefani and Dame-Teixeira.)

Cryptococcosis is a systemic mycosis that causes pneumonia and meningoencephalitis. Strongyloidiasis is a chronic gastrointestinal infection caused by parasites of the genus Strongyloides. Cryptococcosis and strongyloidiasis affect the lungs and are more prevalent in the same world regions, i.e., Africa and tropical countries such as Brazil. It is undeniable that those coincidences may lead to the occurrence of coinfections. However, there are no studies focused on the interaction between Cryptococcus spp. and Strongyloides spp. In this work, we aimed to investigate the interaction between Strongyloides venezuelensis (Sv) and Cryptococcus gattii (Cg) in a murine coinfection model. Murine macrophage exposure to Sv antigens reduced their ability to engulf Cg and produce reactive oxygen species, increasing the ability of fungal growth intracellularly. We then infected mice with both pathogens. Sv infection skewed the host's response to fungal infection, increasing lethality in a murine coinfection model. In addition to increased NO levels and arginase activity, coinfected mice presented a classic Th2 anti-Sv response: eosinophilia, higher levels of alternate activated macrophages (M2), increased concentrations of CCL24 and IL-4, and lower levels of IL-1β. This milieu favored fungal growth in the lungs with prominent translocation to the brain, increasing the host's tissue damage. In conclusion, our data shows that primary Sv infection promotes Th2 bias of the pulmonary response to Cg-infection and worsens its pathological outcomes.

It is not uncommon that oral healthcare professionals and researchers interchange the use of the terms minimum/minimal intervention and minimally invasive dentistry. However, these terms apply to two different, but related, concepts. Minimum intervention dentistry, to be more appropriately addressed in this paper as minimum intervention oral care (MIOC), is an oral healthcare delivery framework that encompasses four interlinked clinical domains. These domains are: identifying disease - detection, longitudinal risk/susceptibility assessment, investigation, diagnosis and the development of a personalized care plan; prevention of lesions/control of disease - patient behaviour management, non-invasive remineralisation of the enamel and dentine, biofilm and diet control, micro-invasive sealants and infiltration techniques to arrest and reverse incipient lesions; minimally invasive operative procedures including selective carious dentine removal, the "5Rs" management of the tooth-restoration complex (review, refurbish, re-seal, repair and replace) amongst other restorative interventions; and tailored recall/review/re-assessment consultations. This framework includes that minimally invasive operative dentistry (MID), that although a critical operative clinical domain, should be viewed as one of the pillars of minimum intervention oral healthcare (MIOC), applied across all disciplines of restorative dentistry, not just caries management. The aim of this review is to clarify these differences and emphasize the importance of minimally invasive operative dentistry (MID) within the context of minimum intervention oral care (MIOC). MIOC is applicable to all disciplines within restorative dentistry, including clinical caries management.

Intestinal ischemia and reperfusion (I/R) is accompanied by an exacerbated inflammatory response characterized by deposition of IgG, release of inflammatory mediators, and intense neutrophil influx in the small intestine, resulting in severe tissue injury and death. We hypothesized that Fc γ RIIb activation by deposited IgG could inhibit tissue damage during I/R. Our results showed that I/R induction led to the deposition of IgG in intestinal tissue during the reperfusion phase. Death upon I/R occurred earlier and was more frequent in Fc γ RIIb -/- than WT mice. The higher lethality rate was associated with greater tissue injury and bacterial translocation to other organs. Fc γ RIIb -/- mice presented changes in the amount and repertoire of circulating IgG, leading to increased IgG deposition in intestinal tissue upon reperfusion in these mice. Depletion of intestinal microbiota prevented antibody deposition and tissue damage in Fc γ RIIb -/- mice submitted to I/R. We also observed increased production of ROS on neutrophils harvested from the intestines of Fc γ RIIb -/- mice submitted to I/R. In contrast, Fc γ RIII -/- mice presented reduced tissue damage and neutrophil influx after reperfusion injury, a phenotype reversed by Fc γ RIIb blockade. In addition, we observed reduced IFN-β expression in the intestines of Fc γ RIII -/- mice after I/R, a phenotype that was also reverted by blocking Fc γ RIIb. IFNAR -/- mice submitted to I/R presented reduced lethality and TNF release. Altogether our results demonstrate that antibody deposition triggers Fc γ RIIb to control IFN-β and IFNAR activation and subsequent TNF release, tailoring tissue damage, and death induced by reperfusion injury., (© 2022 John Wiley & Sons Ltd.)

Introduction: Deficits in neurocognition and social cognition play a critical role in the functional impairment of patients with schizophrenia. Increased oxidative stress has been evidenced in schizophrenia. Increased oxidative stress can affect neuronal function and lead to impairments in neurocognitive functions (especially working memory) and social cognition., Objective: To investigate deficits in neurocognition and social cognition and their potential association with oxidative stress biomarkers in schizophrenia., Material and Methods: Eight-five clinically stable patients with schizophrenia and 75 controls were enrolled in this study. Neurocognition was evaluated through the Brief Assessment of Cognition in Schizophrenia (BACS). Social cognition was assessed through the Hinting Task - a test of theory of mind - and an emotion processing test, Facial Emotion Recognition Test (FERT-100). Oxidative stress was assessed by measuring serum levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)., Results: Patients had decreased serum levels of GSH (Z=3.56; p<0.001) and increased TBARS (Z=5.51; P<0.001) when compared with controls. TBARS levels are higher in patients using first generation antipsychotics. Higher serum levels of TBARS in patients were associated with poor performance in working memory test (r=-0.39; p=0.002), even when controlling for age and negative symptoms (Standard Beta: -0.36; CI= -2.52 a -13.71)., Discussion: The association between greater lipid peroxidation, as assessed by TBARS, and worse performance in working memory corroborates theoretical models of greater vulnerability of schizophrenia to oxidative stress., (Copyright © 2021. Published by Elsevier B.V.)

Objective: In professional sports activities, the search for increased performance is constant. Electrophysical agents, including photobiomodulation (PBM), have been used in the sports context to accelerate postworkout recovery, prevent injuries, and even to improve performance. This study aims to investigate the effects of infrared laser (904 nm) on skeletal muscle gene expression of performance-related proteins of rats submitted to a chronic resistance training protocol. Materials and methods: Male Wistar rats ( n  = 40), weighing ±300 g were divided into four groups: sedentary control (CT, n  = 10); irradiated control (CTL, n  = 10); exercised not irradiated (EX, n  = 10); exercised irradiated (EXL, n  = 10). To assess the performance, the maximum carrying test was adapted and applied 72 h prior the training and 72 h after the last exercise session. The vertical weight climbing protocol was adapted for resistance training 3 × per week with 48 h interval between each session: first week adaptation, second week 25% of body weight (BW), third week 50% BW, fourth week 75% BW, and fifth week 100% BW. Animals were irradiated before exercise on hind paws 50 sec each, with infrared laser 904 nm 5 days per week, during 4 weeks, 9 J per leg in a total of 18 J energy per day. Results: The EXL performed more climbing (7.1 ± 0.91) compared to EX (4.4 ± 0.63). PBM promoted increased expression of lactate dehydrogenase enzyme, mammalian target of rapamycin protein, and androgen receptor ( p  < 0.05) but not the myosin heavy chain ( p  = 0.43). Conclusions: PBM therapy increases the expression of performance-related muscle mass gain genes besides improving the resistance training performance.

Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3 hours and reduced levels after 24 hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC + AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC + AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC + AMB may represent an alternative adjuvant for the treatment of cryptococcosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Adipose tissue is the main energy storage tissue in the body. Its catabolic and anabolic responses depend on several factors, such as nutritional status, metabolic profile, and hormonal signaling. There are few studies addressing the effects of laser photobiomodulation (PBM) on adipose tissue and results are controversial. Objective: Our purpose was to investigate the metabolic effects of PBM on adipose tissue from Wistar rats supplemented or not with caffeine. Materials and methods: Wistar rats were divided into four groups: control (CTL), laser-treated [CTL (L)], caffeine (CAF), and caffeine+PBM [CAF (L)]. Blood was extracted for quantification of triglyceride and cholesterol levels and white adipose tissues were collected for analysis. We evaluated gene expression in the adipose tissue for the leptin receptor, lipase-sensitive hormone, tumor necrosis factor alpha, and beta adrenergic receptor. Results: We demonstrated that the low-level laser irradiation was able to increase the feed intake of the animals and the relative mass of the adipose tissue in the CTL (L) group compared with CTL. Laser treatment also increases serum triglycerides [CTL = 46.99 ± 5.87; CTL (L) = 57.46 ± 14.38; CAF = 43.98 ± 5.17; and CAF (L) = 56.9 ± 6.12; p  = 0.007] and total cholesterol (CTL = 70.62 ± 6.80; CTL (L) = 79.41 ± 13.07; CAF = 71.01 ± 5.52; and CAF (L) = 79.23 ± 6.881; p  = 0.003). Conclusions: Laser PBM decreased gene expression of the studied genes in the adipose tissue, indicating that PBM is able to block the catabolic responses of this tissue. Interestingly, the CAF (L) and CAF animals presented the same CLT (L) phenotype, however, without increasing the feed intake and the relative weight of the adipose tissue. The description of these phenomena opens a new perspective for the study of the action of low-level laser in adipose tissue.

Approximately 180,000 people worldwide die from cryptococcosis each year, probably due to the ineffectiveness and toxicity of drugs currently available to treat the disease. Amphotericin B (AMB) is effective for killing the fungus, but has serious adverse effects linked to excessive production of reactive oxygen species which compromise renal function. Pioglitazone (PIO) is a peroxisome proliferator-activated receptor-γ agonist widely repositioned as an adjuvant of various drugs that have toxic effects due to its antioxidant and anti-inflammatory effects. This study evaluated PIO in combination with AMB for the treatment of cryptococcosis. PIO was found to reduce serum creatinine and glutamic-oxalacetic transaminase levels in mice treated with PIO+AMB. In vitro, PIO was able to control harmful oxidative bursts induced by AMB without compromising the antifungal effect. In vivo, PIO+AMB increased the survival rate compared with AMB alone, and improved the morbidity of the animals. PIO+AMB was more efficient than AMB alone for inhibiting fungal transmigration from the lungs to the brain, and killing yeasts that reached the central nervous system, avoiding the establishment of meningoencephalitis. In a phagocytosis assay, PIO did not influence the engulfment and fungicidal activity of macrophages induced by AMB, but reduced the oxidative bursts after the reduction of fungal burden, pointing to control of the pathogen without leading to excessive stress which can be damaging to the host. In conclusion, PIO+AMB was found to ameliorate cryptococcosis in a murine model, indicating that it is a promising therapeutic adjuvant for combating and controlling this fungal infection., (Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: The lipid metabolism is essential for maintaining the body's energy responses. Laser photobiomodulation triggers many important cellular effects, but these effects on lipid metabolism are not well described. In this study, we analyzed the laser photobiomodulation in the hormone-sensitive lipase (HSL) activity, a key enzyme in the triglycerides (TAG) hydrolysis in adipose tissue 3T3-L1. Methods: Cells were submitted to the differentiation protocol in adipose cells, irradiated with 1, 2, and 3J with laser (904 nm-60 mw-laser diode) and incubated for 4 h after irradiation. Results: The response of laser photobiomodulation was able to trigger an inhibition of HSL activity (control = 0.057 ± 0.0008; 1J = 0.050 ± 0.0003; 2J = 0.0477 ± 0.002; 3J = 0.051 ± 0.002; p  = 0.0003 against the control), but no modulation was observed in TAG levels into the medium (control = 26.5856 ± 0.52; 1J = 26.5856 ± 0.52; 2J = 27.2372 ± 1.41; 3J = 25.9991 ± 0.1303; p  = 0.18). Conclusions: This is the first study of HSL activity modulation with laser radiation, suggesting that photobiomodulation can influence adipose tissue metabolism and open a new field of study.