Maria Raquel Moita

Instituto de Biologia Experimental e Tecnológica

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Luiz Fernando Barbosa de Paulo

Universidade Federal de Uberlândia

J Babulal

Instituto Politécnico de Santarém

Gonçalo Martinho

Instituto Politécnico de Santarém

Tânia Marques

Instituto Politécnico de Leiria

Patrícia Branco

Hospital de Santa Cruz

Florentino Fernandes Mendes

Universidade Federal de Ciências da Saúde de Porto Alegre

Lucas Braga Jaques Gonçalves

Hospital Madre Teresa

Ana Barbas

Instituto de Biologia Experimental e Tecnológica

Sascha Schäuble

Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)

Fabienne Rajas

Inserm

Cooperative Institutions

Universidade Nova de Lisboa

Instituto de Biologia Experimental e Tecnológica

Instituto Politécnico de Santarém

Instituto Gulbenkian de Ciência

University of Lisbon

GenIbet (Portugal)

Instituto de Tecnología Química

Nova Medical (United States)

Friedrich Schiller University Jena

Jena University Hospital

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Iron-mediated control of glucose metabolism is central to promote disease tolerance to polymicrobial infections

Free Radical Biology and Medicine (2018)

Ana Rita Carlos Sebastian Weis Maria Raquel Moita Sumnima Singh Birte Blankenhaus

Gluconeogenesis

Carbohydrate Metabolism

Glucose 6-phosphatase

10.1016/j.freeradbiomed.2018.04.370

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Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis

Frontiers in Cardiovascular Medicine (2022)

Maria Raquel Moita Marta M. Silva Cláudia Diniz Margarida Serra Rene Hoet

Background Activated cardiac fibroblasts (CF) play a central role in cardiac fibrosis, a condition associated with most cardiovascular diseases. Conversion of quiescent into activated CF sustains heart integrity upon injury. However, permanence of CF in active state inflicts deleterious heart function effects. Mechanisms underlying this cell state conversion are still not fully disclosed, contributing to a limited target space and lack of effective anti-fibrotic therapies. Materials and methods To prioritize targets for drug development, we studied CF remodeling upon activation at transcriptomic and proteomic levels, using three different cell sources: primary adult CF (aHCF), primary fetal CF (fHCF), and induced pluripotent stem cells derived CF (hiPSC-CF). Results All cell sources showed a convergent response upon activation, with clear morphological and molecular remodeling associated with cell-cell and cell-matrix interactions. Quantitative proteomic analysis identified known cardiac fibrosis markers, such as FN1, CCN2, and Serpine1, but also revealed targets not previously associated with this condition, including MRC2, IGFBP7, and NT5DC2. Conclusion Exploring such targets to modulate CF phenotype represents a valuable opportunity for development of anti-fibrotic therapies. Also, we demonstrate that hiPSC-CF is a suitable cell source for preclinical research, displaying significantly lower basal activation level relative to primary cells, while being able to elicit a convergent response upon stimuli.

Cardiac Fibrosis

10.3389/fcvm.2022.1015473

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MASQUELET TECHNIQUE AFTER AN INFECTED OSTEOSYNTHESIS OF AN OPEN FRACTURE OF THE FOREARM BONES

Patrícia Branco Luiz Fernando Barbosa de Paulo Ramón González Santos J Babulal Maria Raquel Moita

This work refers to a male patient, 25 years of age, admitted in the Emergency Department following a bicycle accident, of which resulted an open fracture of the right forearm bones – Gustillo & Anderson I.With this work, the authors have as objective the description of the patient's clinical condition – starting with the fracture, over to the osteomyelitis – as well as the surgical procedures and remaining treatments he was submitted to.The authors used the patient's records from Hospital's archives, namely records from the Emergency Department, Operating Room, Infirmary and Consultation, and also the diagnostic exams performed throughout the patient's clinical evolution.This clinical case began in May 2013, when the patient suffered an open fracture of the right forearm bones – Gustillo & Anderson I – due to a bicycle accident. At the time, the exposure site was thoroughly rinsed, a cast immobilization was made, and antibiotics were prescribed. In the fifth day following the trauma, the patient was subm...

Osteosynthesis

Accident and emergency

Open fracture

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Development of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy against Estrogen Receptor-Positive Breast Cancer

Cancers (2021)

Gabriela Silva Joana Sales-Dias Diogo Casal Sara Alves Giacomo Domenici

The Notch-signaling ligand DLL1 has emerged as an important player and promising therapeutic target in breast cancer (BC). DLL1-induced Notch activation promotes tumor cell proliferation, survival, migration, angiogenesis and BC stem cell maintenance. In BC, DLL1 overexpression is associated with poor prognosis, particularly in estrogen receptor-positive (ER+) subtypes. Directed therapy in early and advanced BC has dramatically changed the natural course of ER+ BC; however, relapse is a major clinical issue, and new therapeutic strategies are needed. Here, we report the development and characterization of a novel monoclonal antibody specific to DLL1. Using phage display technology, we selected an anti-DLL1 antibody fragment, which was converted into a full human IgG1 (Dl1.72). The Dl1.72 antibody exhibited DLL1 specificity and affinity in the low nanomolar range and significantly impaired DLL1-Notch signaling and expression of Notch target genes in ER+ BC cells. Functionally, in vitro treatment with Dl1.72 reduced MCF-7 cell proliferation, migration, mammosphere formation and endothelial tube formation. In vivo, Dl1.72 significantly inhibited tumor growth, reducing both tumor cell proliferation and liver metastases in a xenograft mouse model, without apparent toxicity. These findings suggest that anti-DLL1 Dl1.72 could be an attractive agent against ER+ BC, warranting further preclinical investigation.

10.3390/cancers13164074

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MASQUELET TECHNIQUE IN SEPTIC NONUNION OF ULNAR FRACTURE: CLINICAL CASE

Patrícia Branco Luiz Fernando Barbosa de Paulo Carla Días Roberto C. Santos J Babulal

The clinical case refers to a male patient, 34 years old, admitted at the Emergency Department after a fall of 2 meters. Of that trauma, resulted an exposed Monteggia fracture type III – Gustillo & Anderson IIA – on his left arm.With this work, the authors intend to describe the evolution of the patient's clinical condition, as well as the surgical procedures he was submitted to.The authors used the patient's records from Hospital's archives, namely from the Emergency Department, Operating Room, Infirmary and Consultation, and also the diagnostic exams performed throughout the patient's clinical evolution.The clinical case began in December 2011, when the patient suffered a fall of 2 meters in his workplace. From the evaluation in the Emergency Department, it was concluded that the patient presented, at the left forearm, an exposed Monteggia type III fracture – Gustillo & Anderson IIA – combined with a comminuted fracture of the radial head. At the admission day, the wound site was thoroughly rinsed, the ...

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FROM OPEN FRACTURE TO SEPTIC ARTHRITIS: WHEN EVERYTHING GOES WRONG

Patrícia Branco Luiz Fernando Barbosa de Paulo Catarina Dias Renata de Faria Santos J Babulal

This clinical case refers to a male patient, 45 years old, with a past medical history of Hepatitis C, admitted at the Emergency Department on July 2014, after a fall from 7 meters high at his workplace – dump – which resulted in an open fracture of the distal end of the right forearm bones – Gustillo & Anderson IIIA. With this work, the authors aim to describe the evolution of the patient9s clinical status, from the initial fracture to the septic arthritis of the right wrist, as also the surgical interventions and other treatments he has undergone. There were used all patient9s records from Hospital9s archives, including Emergency Department registry, Clinical Diaries, Operative Reports, and results of diagnostic exams. It was also revised all patient9s clinical process, with support of photographs obtained during the successive revaluations. The clinical case we present on this work began on July 2014, when the patient suffered an open fracture – Gustillo & Anderson IIIA – on the distal end of the right forearm bones. The lesion was subjected to washing, closed reduction and internal fixation with Kirschner wires, and also a cycle of antibiotic. At the fourth day after surgery, because of an unfavorable evolution of the wound, the patient was submitted to a bulky abscess drainage and a joint osteotaxis. About 1 month and a half after the traumatic event, it was performed a revision of the osteotaxis, following a failed attempt of osteosynthesis. By unfavorable evolution of the clinical status, with the development of septic arthritis in the right wrist, it was decided to undertake a Masquelet technique. Analyzing the evolution of the patient9s clinical status, the authors conclude that, besides the appropriate therapeutic options taken at each stage, the development of septic arthritis at the right wrist was inevitable. This framework, in association to the fact that this is a 45 years old patient, with the dominant hand affected, raises issues of questionable therapeutic order.

Past medical history

Accidental fall

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FROM OPEN FRACTURE TO SEPTIC ARTHRITIS: WHEN EVERYTHING GOES WRONG

Patrícia Branco Luiz Fernando Barbosa de Paulo Carla Días Rebeca Leite de Oliveira Santos J Babulal

Past medical history

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Metabolic Adaptation Establishes Disease Tolerance to Sepsis

Cell (2017)

Sebastian Weis Ana Rita Carlos Maria Raquel Moita Sumnima Singh Birte Blankenhaus

Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance is a defense strategy against infection that preserves host homeostasis without exerting a direct negative impact on pathogens. Here, we demonstrate that induction of the iron-sequestering ferritin H chain (FTH) in response to polymicrobial infections is critical to establish disease tolerance to sepsis. The protective effect of FTH is exerted via a mechanism that counters iron-driven oxidative inhibition of the liver glucose-6-phosphatase (G6Pase), and in doing so, sustains endogenous glucose production via liver gluconeogenesis. This is required to prevent the development of hypoglycemia that otherwise compromises disease tolerance to sepsis. FTH overexpression or ferritin administration establish disease tolerance therapeutically. In conclusion, disease tolerance to sepsis relies on a crosstalk between adaptive responses controlling iron and glucose metabolism, required to maintain blood glucose within a physiologic range compatible with host survival.

Homeostasis

Gluconeogenesis

Glucose 6-phosphatase

10.1016/j.cell.2017.05.031

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Citations (235)