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Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology often associated with several comorbidities, such as left ventricle pressure overload, diabetes mellitus, obesity, and kidney disease. Its pathophysiology remains obscure mainly due to the complex phenotype induced by all these associated comorbidities and to the scarcity of animal models that adequately mimic HFpEF. Increased oxidative stress, inflammation, and endothelial dysfunction are currently accepted as key players in HFpEF pathophysiology. However, we have just started to unveil HFpEF complexity and the role of calcium handling, energetic metabolism, and mitochondrial function remain to clarify. Indeed, the enlightenment of such cellular and molecular mechanisms represents an opportunity to develop novel therapeutic approaches and thus to improve HFpEF treatment options. In the last decades, the number of research groups dedicated to studying HFpEF has increased, denoting the importance and the magnitude achieved by this syndrome. In the current technological and web world, the amount of information is overwhelming, driving us not only to compile the most relevant information about the theme but also to explore beyond the tip of the iceberg. Thus, this review aims to encompass the most recent knowledge related to HFpEF or HFpEF-associated comorbidities, focusing mainly on myocardial metabolism, oxidative stress, and energetic pathways.

When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a “corona”. This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in pre-clinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size- and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP. The authors acknowledge Rui Fernandes from Histology and Electron Microscopy platform (HEMS) i3s Scientific platform, for the TEM analysis. Tânia Lima was supported by FCT fellowship PD/BD/128393/2017 from BiotechHealth International Doctoral programme. Open access funding provided by Lund University.

Iron acquisition through siderophores, a class of small, potent iron-chelating organic molecules, is a widely spread strategy among pathogens to survive in the iron-restricted environment found in the host. Although these molecules have been implicated in the pathogenesis of several species, there is currently no comprehensive study addressing siderophore production in Staphylococcus epidermidis. Staphylococcus epidermidis is an innocuous skin commensal bacterium. The species, though, has emerged as a leading cause of implant-associated infections, significantly supported by an inherent ability to form biofilms. The process of adaptation from skin niche environments to the hostile conditions during invasion is yet not fully understood. Herein, we addressed the possible role of siderophore production in S. epidermidis virulence. We first identified and deleted a siderophore homolog locus, sfaABCD, and provided evidence for its involvement in iron acquisition. Our findings further suggested the involvement of siderophores in the protection against oxidative stress-induced damage and demonstrated the in vivo relevance of a siderophore-mediated iron acquisition during S. epidermidis infections. Conclusively, this study addressed, for the first time in this species, the underlying mechanisms of siderophore production, highlighting the importance of a siderophore-mediated iron acquisition under host relevant conditions and, most importantly, its contribution to survival within the host., This study was supported by the Portuguese Foundation for Science and Technology (FCT) through the funded project PTDC/BIAMOL/29553/2017, under the scope of COMPETE2020 (POCI-01-0145-FEDER-029553), and the strategic funding of UID/BIO/04469/2019 unit. This study was also supported through funds from the German Research Council (DFG) and the Damp Foundation. FO was supported by an individual Ph.D. scholarship (SFRH/BD/101399/2014)., The authors acknowledge the support of the i3S Scientific Platform HEMS, member of the PPBI (PPBIPOCI-01-0145-FEDER-022122)., info:eu-repo/semantics/publishedVersion

Prostate cancer (PCa) is one of the most common cancer types among men. The quantification of prostate-specific antigen used for PCa detection has revealed limited applicability. Thus, it is crucial to identify new minimally invasive biomarkers for PCa. It is believed that the integration of proteomics data from different studies is vital for identifying new biomarkers for PCa, but studies carried out in this regard have few converging results. Using a different approach, this study aimed to unveil molecular features consistently dysregulated in PCa and potential urinary biomarkers for PCa. The novelty of this analysis relies on the comparison of urinary and tissue proteomes from PCa patients and consequent exclusion of kidney and bladder cancer interference. The conducted bioinformatic analysis revealed molecular processes dysregulated in urine from PCa patients that mirror the alterations in prostate tumor tissue. To identify putative urinary biomarkers, proteins previously detected in kidney and bladder tissues were eliminated from the final list of potential urinary biomarkers for PCa. After a detailed analysis, MSMB, KLK3, ITIH4, ITIH2, HPX, GP2, APOA2 and AZU1 proteins stood out as candidate urinary biomarkers for PCa.

Background: Often, pressure overload–induced myocardial remodeling does not undergo complete reverse remodeling after decreasing afterload. Recently, mitochondrial abnormalities and oxidative stress have been successively implicated in the pathogenesis of several chronic pressure overload cardiac diseases. Therefore, we aim to clarify the myocardial energetic dysregulation in (reverse) remodeling, mainly focusing on the mitochondria. Methods: Thirty-five Wistar Han male rats randomly underwent sham or ascending (supravalvular) aortic banding procedure. Echocardiography revealed that banding induced concentric hypertrophy and diastolic dysfunction (early diastolic transmitral flow velocity to peak early-diastolic annular velocity ratio, E/E′: sham, 13.6±2.1, banding, 18.5±4.1, P =0.014) accompanied by increased oxidative stress (dihydroethidium fluorescence: sham, 1.6×10 8 ±6.1×10 7 , banding, 2.6×10 8 ±4.5×10 7 , P Results: Two weeks later, hypertrophy decreased with the decline of oxidative stress (dihydroethidium fluorescence: banding, 2.6×10 8 ±4.5×10 7 , debanding, 1.96×10 8 ±6.8×10 7 , P P =0.029). The reduction of energetic demands imposed by overload relief allowed the mitochondria to reduce its activity and myocardial levels of phosphocreatine, phosphocreatine/ATP, and ATP/ADP to normalize in debanding towards sham values (phosphocreatine: sham, 38.4±7.4, debanding, 35.6±8.7, P =0.71; phosphocreatine/ATP: sham, 1.22±0.23 debanding, 1.11±0.24, P =0.59; ATP/ADP: sham, 6.2±0.9, debanding, 5.6±1.6, P =0.66). Despite the decreased mitochondrial area, complex III and V expression increased in debanding compared with sham or banding. Autophagy and mitophagy-related markers increased in banding and remained higher in debanding rats. Conclusions: During compensatory and maladaptive hypertrophy, mitochondria become more active. However, as the disease progresses, the myocardial energetic demands increase and the myocardium becomes energy deficient. During reverse remodeling, the concomitant attenuation of cardiac hypertrophy and oxidative stress allowed myocardial energetics, left ventricle hypertrophy, and diastolic dysfunction to recover. Autophagy and mitophagy are probably involved in the myocardial adaptation to overload and to unload. We conclude that these mitochondrial reversible changes underlie diastolic function adaptations during myocardial (reverse) remodeling.

Aortic Stenosis (AS) is the most frequent valvulopathy in the western world. Traditionally aortic valve replacement (AVR) has been recommended immediately after the onset of heart failure (HF) symptoms. However, recent evidence suggests that AVR outcome can be improved if performed earlier. After AVR, the process of left ventricle (LV) reverse remodelling (RR) is variable and frequently incomplete. In this study, we aimed at detecting mechanism underlying the process of LV RR regarding myocardial structural, functional and molecular changes before the onset of HF symptoms. Wistar-Han rats were subjected to 7-weeks of ascending aortic-banding followed by a 2-week period of debanding to resemble AS-induced LV remodelling and the early events of AVR-induced RR, respectively. This resulted in 3 groups: Sham (n = 10), Banding (Ba, n = 15) and Debanding (Deb, n = 10). Concentric hypertrophy and diastolic dysfunction (DD) were patent in the Ba group. Aortic-debanding induced RR, which promoted LV functional recovery, while cardiac structure did not normalise. Cardiac parameters of RV dysfunction, assessed by echocardiography and at the cardiomyocyte level prevailed altered after debanding. After debanding, these alterations were accompanied by persistent changes in pathways associated to myocardial hypertrophy, fibrosis and LV inflammation. Aortic banding induced pulmonary arterial wall thickness to increase and correlates negatively with effort intolerance and positively with E/e′ and left atrial area. We described dysregulated pathways in LV and RV remodelling and RR after AVR. Importantly we showed important RV-side effects of aortic constriction, highlighting the impact that LV-reverse remodelling has on both ventricles.

Non-puerperal uterine inversion is a rare clinical entity and usually occurs as a prolapse of a benign or malignant mass located at the fundus of the uterus. Mechanism for its occurrence remains no...

We evaluated the potential of a liposomal antigen delivery system (ADS) containing Candida albicans cell wall surface proteins (CWSP) in mediating protection against systemic candidiasis. Treatment of bonemarrow- derived dendritic cells with CWSP-loaded dioctadecyldimethylammonium bromide:monoolein (DODAB:MO) liposomes enhanced and prolonged their activation comparatively to free antigen, indicating that liposome-entrapped CWSP were released more sustainable. Therefore, we immunized mice with CWSP either in a free form or loaded into two different DODAB:MO liposome formulations, respectively designated as ADS1 and ADS2, prior to intravenous C. albicans infection. Immunization with ADS1, but not with ADS2, conferred significant protection to infected mice, comparatively to immunization with CWSP or empty liposomes as control. ADS1-immunized mice presented significantly higher serum levels of C. albicans-specific antibodies that enhanced phagocytosis of this fungus. In these mice, a mixed cytokine production profile was observed encompassing IFN-c, IL-4, IL-17A and IL-10. Nevertheless, only production of IL-4, IL-17 and IL-10 was higher than in controls. In this study we demonstrated that DODAB:MO liposomes enhance the immunogenicity of C. albicans antigens and host protection in a murine model of systemic candidiasis. Therefore, this liposomal adjuvant could be a promising candidate to assess in vaccination against this pathogenic fungus., This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI). Catarina Carneiro holds scholarship SFRH/BD/69068/2010. We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda for access to their equipment.

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcimb.2021.803134/ full#supplementary-material, Staphylococcus epidermidis biofilm cells are characterized by increased antimicrobial tolerance and improved ability to evade host immune system defenses. These features are, in part, due to the presence of viable but non-culturable (VBNC) cells. A previous study identified genes potentially involved in VBNC cells formation in S. epidermidis biofilms, among which SERP1682/1681 raised special interest due to their putative role as a toxinantitoxin system of the mazEF family. Herein, we constructed an S. epidermidis mutant lacking the mazEF genes homologues and determined their role in (i) VBNC state induction during biofilm formation, (ii) antimicrobial susceptibility, (iii) survival in human blood and plasma, and (iv) activation of immune cells. Our results revealed that mazEF homologue did not affect the proportion of VBNC cells in S. epidermidis 1457, refuting the previous hypothesis that mazEF homologue could be linked with the emergence of VBNC cells in S. epidermidis biofilms. Additionally, mazEF homologue did not seem to influence key virulence factors on this strain, since its deletion did not significantly affect the mutant biofilm formation capacity, antimicrobial tolerance or the response by immune cells. Surprisingly, our data suggest that mazEF does not behave as a toxinantitoxin system in S. epidermidis strain 1457, since no decrease in the viability and culturability of bacteria was found when only the mazF toxin homologue was being expressed., This work was supported by the Portuguese Foundation for Science and Technology (FCT) by the funder project PTDC/BIA-MOL/29553/2017, under the scope of COMPETE2020 (POCI-01-0145-FEDER-029553) and by the strategic funding unit UIDB/04469/2020. VG acknowledges the support of FCT individual fellowship [SFRH/BD/131452/2017]., info:eu-repo/semantics/publishedVersion