Search

Since the start of the pandemic, scientists have directed their research towards identifying COVID-19 risk factors and predictive elements. Numerous clinical studies have established a strong connection between hypoalbuminemia and an unfavorable prognosis for COVID-19. Here, we aim to explore the impact of human serum albumin (HSA) on SARS-CoV-2 infection. Our findings indicate that HSA plays a role in reducing the replication rate of SARS-CoV-2 in Vero E6 cells. This protective effect is due to HSA ability to bind to the S1 domain of the spike protein, effectively competing with ACE2. Moreover, we show that the protective role of HSA is dependent also on its ability to activate the protective axis within the RAS system pathway, which is responsible for inducing vasodilation and promoting anti-inflammatory, anti-fibrotic, and anti-apoptotic responses. In summary, the data presented in this study support the idea that reduced levels of circulating HSA in hypoalbuminemic patients may heighten their susceptibility to SARS-CoV-2 infection, as the spike protein is unhindered in its ability to bind to ACE2 and penetrate human cells. Besides, hypoalbuminemia exacerbates the imbalance of the RAS pathway towards the classical “detrimental” axis. This could potentially contribute to the increased severity and elevated mortality rate observed in individuals with low levels of circulating albumin.

This technical report illustrates the technique to perform computed tomography (CT)-guided bone biopsies in the body and dens of the axis (C2 vertebra) through a posterior transpedicular approach with the use of preoperative contrast-enhanced scans to highlight the course of the vertebral artery. The technique is presented through two exemplification cases: a pediatric patient with osteoblastoma and secondary aneurysmal bone cyst and one adult patient with melanoma metastasis. This case highlights the potential of the CT-guided posterolateral/transpedicular approach for performing safe and effective biopsies in the body and dens of C2, even in pediatric patients.

Background: Dalbavancin is a long-acting lipoglycopeptide, approved for treatment of skin and skin structure infections. Its PK/PD profile and safety allow for short hospital stays even in the case of difficult-to-treat infections requiring long courses of therapy, e.g., osteomyelitis, cardiovascular, and prosthetic infections. Objectives: We aimed to evaluate the safety and efficacy of dalbavancin in real life settings for both in-label and off-label indications. Methods: retrospective evaluation of all consecutive patients treated with dalbavancin at our site between May 2017 and September 2021. Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson Comorbidity Index CCI = 2.7, 28% inpatients) were included with the following indications: acute bacterial skin and skin structure infections (22%), bone and prosthetic infections (57%), and cardiovascular infections (19%). Infections were caused by MSSA (30%), MRSA (5%), MR-CoNS (20%), and Streptococcus spp. (8%). In 32 cases, no isolate was obtained. The average number of infusions was 5 (s.d. = 3). Neither ensuing alteration of renal function nor neutropenia or thrombocytopenia were observed during treatment and follow-up. Two self-limiting skin rashes occurred. The overall clinical success rate was 84%—91% for registered and 82% for unregistered indications. The prescription of higher loading doses was the only predictor independently associated with better outcomes in multivariate models (OR: 5.2, 95%CI: 1.5–17.9, p < 0.01). Conclusions: Dalbavancin proved to be effective for skin and skin structure infections, as well as for difficult-to-treat infections in highly comorbid patients. Regarding tolerability, our results support the use of dalbavancin for long-lasting treatments of deep-seated infections.

Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes related to the different binding modes of NO to heme-Fe(II), as well as the modulatory effects of this diatomic messenger on heme-protein functions. Specifically, the ability of heme proteins to bind NO at either the distal or proximal side of the heme and the transient interchanging of the binding site is reported. This sheds light on the regulation of O2 supply to tissues with high metabolic activity, such as the retina, where a precise regulation of blood flow is necessary to meet the demand of nutrients.

Herein, chemometric-assisted synthesis of electrochemical sensors based on electropolymerised ion-imprinted polymeric (e-IIP) films was explored. Co(II)-IIPs sensors were prepared by performing electropolymerisation procedures of polymerisation mixtures comprising varying concentrations of an electroactive o-aminophenol (o-AP) monomer and Co(II) ions, respectively, according to the Taguchi L9 experimental design, exploiting the simultaneous evaluation of other controlled parameters during electrosynthesis. Each e-IIP developed from Taguchi runs was compared with the respective non-imprinted polymer (NIP) films and fitted according to Langmuir–Freudlich isotherms. Distinctive patterns of low and high-affinity films were screened based on the qualities and properties of the developed IIPs in terms of binding kinetics (KD), imprinting factor, and the heterogeneity index of produced cavities. These results can provide a generic protocol for chemometric-assisted synthesis of e-IIPs based on poly-o-AP, providing highly stable, reproducible, and high-affinity imprinted polymeric films for monitoring purposes.

ABSTRACT: Hydatid disease (HD) is a zoonotic parasitic disease caused by the larvae of Echinococcus. Bone echinococcosis is rare, accounting for 0.5% to 4% of all echinococcosis. We describe a particular case of pelvic echinoccosis. A 29-year-old man initially presents with pain in his left hip for several years. After an accidental fall from a tree, he suffered a fracture of the left acetabulum. X-rays and CT scans showed an osteolytic area of the acetabulum with bony cortical interruption. MR imaging demonstrated extensive area of osteostructural alteration of the iliac wing and the left acetabulum due to multiple cysts with enhancement of the walls after administration of Gadolinium-based contrast agents. A CT-guided biopsy of an osteolytic area was performed with diagnosis of echinococcus cyst. He underwent albendazole therapy and subsequently echinococcus cyst exeresis, bone curettage, and left hip arthroplasty. Twenty-two months after surgery, CT scan showed recurrence of disease. After 4 years and 6 months of chronic therapy CT scan showed an increase in size of the cyst at the site of the disease recurrence. Five years and 4 months after the first operation, a new cyst exeresis and pelvic bone curettage with implant retention was performed. This case report demonstrates that hydatid cysts should be considered as a possible cause for non-specific pelvic pain, especially in endemic locations.

O objetivo do presente estudo foi comparar a PA após uma sessão de treinamento concorrente (TC) e as atividades lúdicas (AL) em pessoas vivendo com HIV (PVHIV) e analisar a contribuição da resistência periférica e baroreflexo na PA. Participaram do estudo 15 pessoas que vivem com HIV, 9 mulheres e 6 homens com 50,54 ± 10,81 anos, tempo de uso da TARV de 9,17 ± 4,97 anos. Todos os voluntários participaram de uma sessão de TC, de uma de AL e outra na condição controle (CC). Foram aferidos PA e frequência cárdica (FC) pré e pós as intervenções para analises da pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), resistência periférica total (RPT) e baixa frequência (BF). Foram realizados os testes de Shapiro-Wilk, Friedman e Wilcoxon, o nível de significância foi de p

O surgimento do HIV impactou os serviços de saúde abruptamente em 1981, inicialmente afetando grupos sociais restritos. Atualmente, com o desenvolvimento da terapia antirretroviral, nos deparamos com uma doença diferente da encarada na década de 80, agora com uma evolução crônica. Todavia, algumas barreiras permanecem as mesmas, como o impacto social, mental e físico do diagnóstico na vida da pessoa que vive com HIV. O objetivo do presente estudo é verificar carga viral, contagem de linfócitos CD4+, e qualidade de vida de pessoas que vivem com o vírus da imunodeficiência humana. A presente pesquisa trata-se de um estudo observacional transversal com amostra de 24 indivíduos de ambos os sexos, com sorologia positiva para HIV, em acompanhamento médico sob tratamento antirretroviral. Foi utilizado um instrumento próprio para a coleta de informações sociodemográficas. Os resultados de contagem de CD4+ e a Carga Viral do HIV foram coletados dos prontuários médicos dos pacientes. A Qualidade de vida (QV) foi avaliada através do WHOQOL-HIV-BREF. Foi utilizada a análise descritiva para a caracterização do perfil da amostra. Os participantes ( = 46,8 possuem ensino médio completo (41,8%), com renda de um a três salários mínimos (37,5%). Apresentam de um a três anos de diagnóstico e contagem de linfócitos CD4 acima de 500 mm3 de sangue (75%). Em relação à QV, os participantes apresentaram média mais alta para o domínio físico (26,7±5,3) e mais baixa para os domínios de meio ambiente (10,9 ± 2,7) e relações sociais (12,2±2,8). O estudo conclui que as pessoas que vivem com HIV participantes do estudo são adultos jovens, com renda e nível de escolaridade baixas, apresentam baixa qualidade de vida em relação aos domínios meio ambiente e relações sociais.

O objetivo do estudo foi criar e determinar uma bateria de avaliação da coordenação motora em crianças com transtorno do espectro autista – BACMA. Este estudo é descritivo, transversal e exploratório para verificação da validade de conteúdo e de aparência do BACMA, por meio da metodologia Delphi, com consulta a um quadro de especialistas no tratamento de crianças com Transtorno do Espectro Autista - TEA. Os critérios de inclusão foram profissionais da área da saúde e educação formados, atuantes, mais de dois anos de experiência no atendimento de crianças com TEA e, como critério de exclusão, respostas incompletas e a não continuidade dos respondentes nas rodadas do Delphi. O quadro de especialistas foi constituído inicialmente por 23 profissionais (01 psicologia, 03 pedagogia, 05 fisioterapia e 14 educação física), todos com atuação relacionada a crianças com TEA. A versão final do BACMA é composta por quatro testes que se destinam a avaliar as habilidades motoras fundamentais: locomoção, manipulação, equilíbrio e salto, conforme o link https://bit.ly/bacmaresultado. Por fim o procedimento que determina a objetividade, alcançou um índice de concordância de 100% na quarta rodada, com um coeficiente ∝ de Cronbach= 0,99, o que indica uma confiabilidade estatisticamente elevada.

The Manifesto serves as a unifying framework for academics, degree courses, departments, schools and universities seeking to institutionalise service-learning into their curriculum. It has been developed by the Italian Universities Network for Service-Learning (UNiSL). It represents the initial outcome of a comprehensive analysis of research findings and documented experiences from Italy and abroad. This document introduces the Italian definition of service-learning in higher education, accompanied by a glossary consisting of nine key terms, each followed by an explanatory description. Its primary objective is to comprehensively understand the approaches, theoretical models and perspectives that characterise the Network. Il Manifesto della Rete delle Università italiane per il Service-Learning (UNiSL). Il Manifesto intende offrire una piattaforma comune per docenti, Corsi di Laurea, Dipartimenti, Scuole o Atenei che intendano istituzionalizzare il service-learning all’interno del proprio curriculum. Il documento è stato elaborato dalla Rete delle UNiversità Italiane per il Service-Learning (UNiSL) e rappresenta un primo risultato raggiunto grazie al confronto sugli esiti delle ricerche condotte e sulle esperienze documentate in Italia e all’estero. Nel documento si propone la definizione italiana di service-learning in contesto universitario e un glossario con nove parole chiave, ognuna accompagnata da una spiegazione, con l’obiettivo di comprendere in modo esaustivo gli approcci, i modelli teorici e le prospettive che caratterizzano la Rete.

The aim of this thematic analysis is to understand in which contexts of higher education service-learning approach is implemented, and how much it is employed in the field of inclusion. Further objective of this thematic analysis is to understand what role within service-learning projects is reserved for students with special educational needs. Are students with disabilities only recipients of service-learning projects or are they actors and promoters? Are service-learning experiences promoting these student’s agency? Service-learning e inclusione nei contesti universitari. Una thematic analysis. Lo scopo della thematic analysis è capire in quali contesti accademici viene implementato il service-learning, e quanto è impiegato nel campo dell’inclusione. Ulteriore obiettivo è comprendere quale ruolo viene riservato agli studenti con bisogni educativi speciali all’interno dei progetti di service-learning. Gli studenti con disabilità sono solo destinatari di progetti di service-learning o ne sono attori e promotori? Le esperienze di service-learning promuovono l’agency personale di questi studenti?

Il Service-Learning nel contesto universitario: uno sguardo critico

Background/Objectives: Diabetes is a well-recognised factor inducing a plethora of corneal alterations ranging from dry eye to reduced corneal sensibility, epithelial defects, and reduced cicatrisation. This cohort study aimed to assess the efficacy of a novel ophthalmic solution combining cross-linked hyaluronic acid (CHA), chondroitin sulfate (CS), and inositol (INS) in managing diabetes-induced corneal alterations. Specifically, it evaluated the solution's impact on the tear breakup time (TBUT), the ocular surface disease index (OSDI), and corneal sensitivity after three months of treatment. Additionally, the solution's potential to promote wound healing was examined. Methods: Two different populations were retrieved from the database; the first one was composed of 20 diabetic subjects treated for three months with the ophthalmic CAH-CS (OPHTAGON srl, Rome, Italy), while the second group was composed of 20 diabetic subjects who did not want to use any eye lubricant or other treatment. The outcome measures were the TBUT, the OSDI score, and the corneal sensitivity measured using a Cochet–Bonnet aesthesiometer. To investigate the wound-healing properties, in vitro tests were conducted using two cell lines, comparing the results of scratch tests with and without the solution. Results: The results indicate that CHA-CS significantly improved the tear film stability, as evidenced by an increased TBUT and a reduction in dry eye symptoms reflected by lower OSDI scores. Moreover, the solution was associated with an enhanced corneal sensitivity in treated patients. In wound-healing assays, CHA-CS promoted cell motility, suggesting a supportive role in tissue repair compared to untreated cells. Conclusions: Collectively, the results suggest that CHA-CS could serve as an innovative tool for the treatment of diabetic patients with corneal alterations and delayed corneal sensitivity. Clinical trial registration number: Clinical Trial.gov NCT06573606. [ABSTRACT FROM AUTHOR]

Abstract Background Challenges exist in the clinical treatment of luminal estrogen receptor α (ERα)-positive breast cancers (BCs) both to prevent resistance to endocrine therapy (ET) and to treat ET-resistant metastatic BCs (MBC). Therefore, we evaluated if kinases could be new targets for the treatment of luminal primary and MBCs. Methods ~ 170 kinase inhibitors were applied to MCF-7 cells either with adaptative or genetic resistance to ET drugs and both ERα levels and cell proliferation were measured. Robust-Z-score calculation identified AZD7762 (CHK1/CHK2 inhibitor) as a positive hit. Subsequently, Kaplan–Meier analyses of CHK1 and CHK2 impact on ERα-positive BC patients relapse-free-survival (RFS), bioinformatic evaluations of CHK1 and CHK2 expression and activation status as a function of ERα activation status as well as drug sensitivity studies in ERα-positive BC cell lines, validation of the impact of the ATR:CHK1 and ATM:CHK2 pathways on the control of ERα stability and BC cell proliferation via inhibitor- and siRNA-based approaches, identification of the molecular mechanism required for inhibitor-dependent ERα degradation in BC and the impact of CHK1 and CHK2 inhibition on the 17β-estradiol (E2):ERα signaling, synergy proliferation studies between ET-drugs and clinically relevant CHK1 inhibitors in different luminal BC cell lines, were performed. Results A reduced CHK1 expression correlates with a longer RFS in women with ERα-positive BCs. Interestingly, women carrying luminal A BC display an extended RFS when expressing low CHK1 levels. Accordingly, CHK1 and ERα activations are correlated in ERα-positive BC cell lines, and the ATR:CHK1 pathway controls ERα stability and cell proliferation in luminal A BC cells. Mechanistically, the generation of DNA replication stress rather than DNA damage induced by ATR:CHK1 pathway inhibition is a prerequisite for ERα degradation. Furthermore, CHK1 inhibition interferes with E2:ERα signaling to cell proliferation, and drugs approved for clinical treatment of primary and MBC (4OH-tamoxifen and the CDK4/CDK6 inhibitors abemaciclib and palbociclib) exert synergic effects with the CHK1 inhibitors in clinical trials for the treatment of solid tumors (AZD7762, MK8776, prexasertib) in preventing the proliferation of cells modeling primary and MBC. Conclusions CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs.

Low serum albumin (SA) correlates with mortality in critically ill patients, including those with COVID-19. We aimed to identify SA thresholds to predict the risk of longer hospital stay, severe respiratory failure, and death in hospitalized adult patients with COVID-19 pneumonia. A prospective longitudinal study was conducted at the Infectious Diseases Unit of Trieste University Hospital (Italy) between March 2020 and June 2021. The evaluated outcomes were: (1) need of invasive mechanical ventilation (IMV); (2) length of hospital stay (LOS); and (3) 90-day mortality rate. We enrolled 864 patients. Hypoalbuminemia (p < 0.001). The optimal SA cutoff predicting the need of IMV was 3.17 g/dL (AUC 0.688; 95% CI: 0.618–0.759; p < 0.001) and this threshold appeared as an independent risk factor for the risk of IMV in multivariate Cox regression analysis. The median LOS was 12 days and a higher SA was predictive for a shorter LOS (p < 0.001). The overall 90-day mortality rate was 15%. SA was significantly lower in patients who died within 90 days from hospital admission (3.1 g/dL; IQR 2.8–3.4; p < 0.001) as compared to those who survived (3.4 g/dL; IQR 3.1–3.7). The optimal SA threshold predicting high risk of 90-day mortality was 3.23 g/dL (AUC 0.678; 95% CI: 0.629–0.734; p < 0.001). In a multivariate Cox regression analysis, SA of

Abstract Pharmacological inhibition of phosphodiesterase 2A (PDE2A), which catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), has recently been proposed as a novel therapeutic tool for Fragile X Syndrome (FXS), the leading monogenic cause of Autism Spectrum Disorder (ASD). Here, we investigated the role of PDE2A in ASD pathogenesis using two rat models that reflect one of either the genetic or environmental factors involved in the human disease: the genetic Fmr1- Δ exon 8 rat model and the environmental rat model based on prenatal exposure to valproic acid (VPA, 500 mg/kg). Prior to behavioral testing, the offspring was treated with the PDE2A inhibitor BAY607550 (0.05 mg/kg at infancy, 0.1 mg/kg at adolescence and adulthood). Socio-communicative symptoms were assessed in both models through the ultrasonic vocalization test at infancy and three-chamber test at adolescence and adulthood, while cognitive impairments were assessed by the novel object recognition test in Fmr1- Δ exon 8 rats (adolescence and adulthood) and by the inhibitory avoidance test in VPA-exposed rats (adulthood). PDE2A enzymatic activity in VPA-exposed infant rats was also assessed. In line with the increased PDE2A enzymatic activity previously observed in the brain of Fmr1-KO animals, we found an altered upstream regulation of PDE2A activity in the brain of VPA-exposed rats at an early developmental age (p

Objetivo: Analisar, através de uma revisão sistemática, os efeitos do treinamento resistido, aeróbico e de flexibilidade e suas adaptações crônicas na saúde do idoso. Métodos: Trata-se de um estudo de revisão sistemática da literatura, que partiu da estratégia PICo para a formulação da questão norteadora e seguiu as recomendações PRISMA Flow, realizada nas bases de dados Web of Science, SciELO, BVS e Trip database através dos descritores: Idoso, Exercício e Flexibilidade, bem como suas traduções para o espanhol e inglês, de acordo com os DeCS e o MeSh. Resultados. A amostra nos estudos variou de 17 a 420 idosos de ambos os sexos, com 90,9% dos estudos avaliando a flexibilidade em diferentes intervenções. De acordo com os resultados, pode observar em relação ao tipo de estudo que o mais utilizado foi o de ensaio clínico randomizado (ECR) com 21,42%, seguido por Caso Controle e estudo experimental com 17,85%. Levando-se em consideração o Protocolo de Exercícios: Testes aplicados, o mais empregado foi o teste de flexibilidade (Banco de Wells - Sentar e Alcançar) com 54,54%. Ressalta-se que 100% dos estudos relataram melhoras significativas do treinamento resistido na flexibilidade, força, e equilíbrio e composição corporal dos idosos, com impactos positivos em sua autonomia funcional. Conclusão: exercício físico para idosos, desde que executado dentro de volume e intensidade adequados e respeitando os princípios do treinamento desportivo, atuam de forma significativa na melhora dos componentes do condicionamento físico, melhorando sua autonomia funcional, proporcionando um envelhecimento saudável. Palavras-Chave: Idosos. Exercício. Flexibilidade.

The zebrafish (Danio rerio) has emerged as a valuable model for studying host-pathogen interactions due to its unique combination of characteristics. These include extensive sequence and functional conservation with the human genome, optical transparency in larvae that allows for high-resolution visualization of host cell-microbe interactions, a fully sequenced and annotated genome, advanced forward and reverse genetic tools, and suitability for chemical screening studies. Despite anatomical differences with humans, the zebrafish model has proven instrumental in investigating immune responses and human infectious diseases. Notably, zebrafish larvae rely exclusively on innate immune responses during the early stages of development, as the adaptive immune system becomes fully functional only after 4–6 weeks post-fertilization. This window provides a unique opportunity to isolate and examine infection and inflammation mechanisms driven by the innate immune response without the confounding effects of adaptive immunity. In this review, we highlight the strengths and limitations of using zebrafish as a powerful vertebrate model to study innate immune responses in infectious diseases. We will particularly focus on host-pathogen interactions in human infections caused by various bacteria (Clostridioides difficile, Staphylococcus aureus, and Pseudomonas aeruginosa), viruses (herpes simplex virus 1, SARS-CoV-2), and fungi (Aspergillus fumigatus and Candida albicans). [ABSTRACT FROM AUTHOR]

Background: Dalbavancin is a long-acting lipoglycopeptide, approved for treatment of skin and skin structure infections. Its PK/PD profile and safety allow for short hospital stays even in the case of difficult-to-treat infections requiring long courses of therapy, e.g., osteomyelitis, cardiovascular, and prosthetic infections. Objectives: We aimed to evaluate the safety and efficacy of dalbavancin in real life settings for both in-label and off-label indications. Methods: retrospective evaluation of all consecutive patients treated with dalbavancin at our site between May 2017 and September 2021. Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson Comorbidity Index CCI = 2.7, 28% inpatients) were included with the following indications: acute bacterial skin and skin structure infections (22%), bone and prosthetic infections (57%), and cardiovascular infections (19%). Infections were caused by MSSA (30%), MRSA (5%), MR-CoNS (20%), and Streptococcus spp. (8%). In 32 cases, no isolate was obtained. The average number of infusions was 5 (s.d. = 3). Neither ensuing alteration of renal function nor neutropenia or thrombocytopenia were observed during treatment and follow-up. Two self-limiting skin rashes occurred. The overall clinical success rate was 84%—91% for registered and 82% for unregistered indications. The prescription of higher loading doses was the only predictor independently associated with better outcomes in multivariate models (OR: 5.2, 95%CI: 1.5–17.9, p < 0.01). Conclusions: Dalbavancin proved to be effective for skin and skin structure infections, as well as for difficult-to-treat infections in highly comorbid patients. Regarding tolerability, our results support the use of dalbavancin for long-lasting treatments of deep-seated infections. [ABSTRACT FROM AUTHOR]

Polyfluoroalkyl compounds (PFASs) are synthetic compounds recently classified as permanent and emerging chemicals ever since their bioaccumulation in humans and the environment, due to the presence of carbon–fluorine functional groups. The design of novel screening tools with addressed high response time for the routine quantification of PFASs in water is highly desirable. In this work, we propose the preparation of a new voltammetric sensor based on molecularly imprinted polymer nanoparticle (nanoMIP) receptors for the highly sensitive and selective quantification of PFASs in water. The nanoMIPs were synthesized by the solid phase approach and immobilized onto functionalized screen-printed platinum electrode (SPPtE), chosen as the transduction element for sensor development. Dimensional characterization of nanoMIPs by Dynamic light scattering (DLS) shows small nanosized imprinted particles (

Heme is the reactive center of several metal-based proteins that are involved in multiple biological processes. However, free heme, defined as the labile heme pool, has toxic properties that are derived from its hydrophobic nature and the Fe-atom. Therefore, the heme concentration must be tightly controlled to maintain cellular homeostasis and to avoid pathological conditions. Therefore, different systems have been developed to scavenge either Hb (i.e., haptoglobin (Hp)) or the free heme (i.e., high-density lipoproteins (HDL), low-density lipoproteins (LDL), hemopexin (Hx), and human serum albumin (HSA)). In the first seconds after heme appearance in the plasma, more than 80% of the heme binds to HDL and LDL, and only the remaining 20% binds to Hx and HSA. Then, HSA slowly removes most of the heme from HDL and LDL, and finally, heme transits to Hx, which releases it into hepatic parenchymal cells. The Hx:heme or HSA:heme complexes are internalized via endocytosis mediated by the CD91 and CD71 receptors, respectively. As heme constitutes a major iron source for pathogens, bacteria have evolved hemophores that can extract and uptake heme from host proteins, including HSA:heme. Here, the molecular mechanisms underlying heme scavenging and delivery from HSA are reviewed. Moreover, the relevance of HSA in disease states associated with increased heme plasma concentrations are discussed.

Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes related to the different binding modes of NO to heme-Fe(II), as well as the modulatory effects of this diatomic messenger on heme-protein functions. Specifically, the ability of heme proteins to bind NO at either the distal or proximal side of the heme and the transient interchanging of the binding site is reported. This sheds light on the regulation of O2 supply to tissues with high metabolic activity, such as the retina, where a precise regulation of blood flow is necessary to meet the demand of nutrients. [ABSTRACT FROM AUTHOR]