Debora Foguel

Hereditary transthyretin amyloidosis (ATTRv) is a genetic disorder caused by more than 100 autosomal dominant mutations in the TTR gene. Owing to its marked clinical heterogeneity—particularly in its cardiac manifestations—ATTRv is frequently underdiagnosed and requires comprehensive clinical evaluation. The disease commonly presents as a progressive axonal sensorimotor polyneuropathy with autonomic involvement. Despite advances in disease-modifying therapies, including the availability of Tafamidis, delayed diagnosis remains a major challenge, contributing to increased morbidity and mortality. Therefore, the identification of reliable biomarkers for early detection, disease staging, and therapeutic monitoring is essential. One promising candidate is neurofilament light chain (NfL), a structural axonal protein released into the circulation following neuronal injury, which has been proposed as a biomarker of neuroaxonal damage in ATTRv in other populations. The present study aimed to evaluate plasma NfL (pNfL) levels in Brazilian patients with ATTRv and to investigate their association with neuropathy severity. Symptomatic and asymptomatic patients with genetically confirmed ATTRv followed at a specialized university reference center were included, along with healthy volunteer controls. A subgroup of symptomatic patients was receiving Tafamidis therapy. Clinical and demographic data were collected during routine visits, and neuropathy severity was assessed using validated instruments, including the Neuropathy Impairment Score (NIS) and the Polyneuropathy Disability (PND) score. Plasma NfL concentrations were measured using the ultrasensitive SIMOA SR-X platform. Statistical analyses were performed to compare pNfL levels across groups and to assess correlations with clinical parameters. Symptomatic patients not receiving Tafamidis exhibited significantly higher pNfL levels compared with treated symptomatic patients, asymptomatic mutation carriers, and healthy controls. Moreover, pNfL concentrations showed a positive correlation with NIS scores, indicating increasing axonal damage with disease progression. Z-score analyses further supported the ability of pNfL to discriminate between disease stages. In conclusion, plasma NfL emerges as a promising biomarker for assessing disease severity, progression, and treatment response in ATTRv, supporting its potential utility in Brazilian clinical practice.

The cerebral dopamine neurotrophic factor (CDNF) is a neurotrophic factor extensively studied in the central nervous system because of its neuroprotective effects; however, its role in the peripheral nervous system (PNS) remains less explored. In this study, we used primary dorsal root ganglia (DRG) explants to investigate the neuritogenic potential of exogenous CDNF, as well as its neuroprotective activity under trophic factor deprivation. Our findings demonstrate that CDNF‐mediated neuroprotection remains unaffected by the addition of a Trk (tropomyosin receptor kinase) inhibitor or anti‐nerve growth factor (NGF) antibody, indicating that CDNF's neurotrophic activity is independent of TrkA signaling. Furthermore, CDNF binding to KDEL‐receptor (KDEL‐R) was essential for its protective effect, as the CDNF variant lacking the KDEL‐R binding sequence (CDNF‐ΔKTEL) displayed no significant neuroprotection. Additionally, the simultaneous administration of NGF and CDNF to DRG explants resulted in an additive enhancement of their trophic activities. Notably, both CDNF‐ and NGF‐induced neurotrophic effects were PI3K‐dependent, reinforcing the role of this signaling pathway in their mechanisms of action. Taken together, our findings highlight CDNF's crucial role in the PNS, ensuring that NGF‐independent neurogenesis can occur. This suggests that CDNF could be further explored in conditions where NGF levels are low or where NGF signaling inhibition is desirable, such as in chronic pain management. image

Long COVID is characterized by symptoms that persist for more than 12 weeks after a SARS-CoV-2 infection. This study investigated public perceptions of long COVID in Brazil. Interviews were conducted with 1,295 participants selected based on variable quotas, according to the population distribution in each region of the country, using data from the 2021 National Household Sample Survey (PNAD) and the 2010 IBGE Census. The findings revealed that 40.6% reported having had COVID-19 between 2020 and 2023, with 33.4% experiencing persistent symptoms for at least three months. The most common symptoms included fatigue (44.6%), headache (43.7%), hair loss (40.9%), memory loss (34.7%), and difficulty concentrating (28.7%). The study highlights that Brazilians are unaware of the correlation between these symptoms and the acute phase of the disease. By increasing public awareness of the issue, society becomes more capable of demanding better healthcare services for long COVID and insisting on effective policies. The importance of social education on this topic is fundamental to improving the healthcare system.

High hydrostatic pressure (HHP) has been used for viral inactivation to facilitate vaccine development when immunogenicity is maintained or even increased. In this work, we used HHP to inactivate Bothrops jararacussu venom. Our protocol promotes the loss of or decrease in many biological activities in venom. Horses were immunized with pressurized venom, and in contrast to native venom, this procedure does not induce any damage to animals. Furthermore, the serum obtained with pressurized venom efficiently neutralized all biological activities of B. jararacussu venom. Antibody titrations were higher in serum produced with pressurized venom compared to that produced by native venom, and this antivenom was not only effective against the venom of B. jararacussu but against the venom of other species and genera. In conclusion, our data show a new technique for producing hyperimmune serum using venom inactivated by HHP, and this method is associated with a reduction in toxic effects in immunized animals and higher potency.

The Brazilian scientific community, primarily composed of public universities and research institutes, played a fundamental role in combating the COVID-19 pandemic. This study investigates Brazil’s contribution to the global body of knowledge on COVID-19 through publications in scientific journals. Specifically, it analyzes bibliometric indicators of Brazilian scientific publications on COVID-19 between 2019 and 2023, as indexed in the Scopus database. The results demonstrate: 1) there was a global effort to understand the SARS-CoV-2 virus, resulting in significant scientific production; 2) the proportion of publications on the topic was higher in Brazil than in the rest of the world; 3) Brazilian research on COVID-19 covered several knowledge domains; 4) the proportion of joint publications by Brazilian and international scholars was higher on COVID-19 than on other topics; 5) Brazilian public universities responded to the challenge of COVID-19 research, engaging more with international collaboration networks and achieving a higher impact with their publications. The study highlights the importance of national scientific research in shaping public policies and in addressing global health crises. Despite political and funding challenges, the efforts of the Brazilian scientific community were remarkable, reinforcing the importance of sustained investment in science, technology, and innovation.

Anais do Congresso de Fisiologia e Patologia (978-65-272-1162-4) - Cdnf Previne Dano Mitocondrial Por Isquemia/Reperfusão

Nanotechnology is used in several biomedical applications, including antimicrobial and antibiofilm applications using nanomaterials. Bacterial biofilm varies according to the strain; the matrix is very strong and resistant. In this sense, phytosynthesis is an important method for combating bacterial biofilms through the use of metallic nanoparticles (silver, gold, or copper) with increased marketing and technical-scientific potential. In this review, we seek to gather the leading publications on the use of phytosynthesized metallic nanoparticles against bacterial biofilms. Furthermore, this study aims to understand the main characteristics and parameters of these nanomaterials, their antibiofilm efficiency, and the presence or absence of cytotoxicity in these developed technologies.

Procyanidins (PCs) have emerged as agents with potential antimicrobial and antibiofilm activities, although their mechanisms of action and structure-activity relationships remain poorly understood. This review assessed the potential mechanisms of action and applications of these compounds to explore these aspects. Studies on the antimicrobial properties of PCs suggest that they are involved in osmotic imbalance, DNA interactions and metabolic disruption. Although less studied, their antibiofilm activities include antiadhesive effects and the modulation of mobility and quorum sensing. However, most research has used uncharacterized plant extracts for in vitro assays, limiting the understanding of the structure-activity relationships of PCs and their in vivo mechanisms. Clinical trials on the antimicrobial and antibiofilm properties of PCs have not clarified these issues due to nonstandardized methodologies, inadequate chemical characterization, and the limited number of studies, preventing a consensus and evaluation of the in vivo effects. Additionally, patent analysis revealed that technological developments in the antimicrobial and antibiofilm uses of PCs are concentrated in health care and dental care, but new biotechnological uses are emerging. Therefore, while PCs are promising antimicrobial and antibiofilm compounds, further research into their chemical structures and mechanisms of action is crucial for evidence-based applications in biotechnology and health care.