Biology subjects

da Silva, G.

Publications and source records attributed to da Silva, G..

3 recordsLinked to original sources

bioRxiv2026

Nav1.5 expressed in TrkB+ sensory neurons mediates paclitaxel-induced mechanical pain hypersensitivity

Chemotherapy-induced neuropathic pain (CINP) is a frequent and debilitating adverse effect of anti-tumor therapies, for which current treatments are largely non-specific and offer limited efficacy. Identifying molecular mechanisms that drive CINP may enable the development of targeted therapeutic strategies. Here, we demonstrate that paclitaxel-induced mechanical pain hypersensitivity in mice occurs independently of classical Nav1.8+ nociceptors but critically depends on TrkB+ sensory neurons. Transcriptomic analysis of TrkB+ sensory neurons revealed selective expression of Scn5a, which encodes the voltage-gated sodium channel Nav1.5, a channel classically associated with cardiac excitability. Importantly, SCN5A expression was also detected in human primary sensory neurons, indicating potential translational relevance. Functional studies further showed that Scn5a knockdown, using small interfering RNA, significantly attenuates paclitaxel-induced mechanical pain hypersensitivity. Together, these findings identify TrkB+ sensory neurons as key drivers of CINP and reveal Nav1.5 as a previously unrecognized contributor to chemotherapy-induced neuropathic pain. Targeting Nav1.5 in TrkB+ sensory neurons may therefore represent a novel therapeutic strategy for the treatment of CINP.

neuroscience↗

bioRxiv2024

IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma

Lymphatic vessels play a crucial role in activating anti-tumor immune surveillance but also contribute to metastasis and systemic tumor progression. Whether distinct lymphatic phenotypes exist that govern the switch between immunity and metastasis remains unclear. Here we reveal that cytotoxic immunity normalizes lymphatic function and uncouples immune and metastatic potential. We find that in mice and humans, intratumoral lymphatic vessel density negatively correlates with productive cytotoxic immune responses and identify IFN{gamma} as an intrinsic inhibitor of lymphangiogenesis. Specific deletion of the Ifngr1 in lymphatic endothelial cells (LECs) greatly expanded the intratumoral lymphatic network and drove the emergence of a tip-like endothelial state, promoting lymph node metastasis but not dendritic cell migration. IFN{gamma} inhibits oxidative phosphorylation, which is required for proliferation and acquisition of the pathologic transcriptional state. Our data indicate that IFN{gamma} induces a phenotypic switch in tumor-associated lymphatic vessels to reinforce canonical immune surveillance and block metastasis.

cancer biology↗

bioRxiv2021

Follow-up of a hospital cohort during the first 3,530 suspected cases of COVID-19 in Sao Jose do Rio Preto, Sao Paulo, Brazil

IntroductionIn a global context, COVID-19 is the most significant health threat in the present days, evidenced by the fact that, in just over four months, SARS-CoV-2 has spread to 171 countries, reaching a Pandemic status. Most patients with COVID-19 have a mild course of the disease. However, approximately 20% develop severe illness with a high mortality rate which is associated with age, comorbidities, and immunosuppression. Epidemiological studies are used to reveal the extent of viral spread in homes, communities, and hospitals. Thus, preventive and control measures can be established by the authorities. ObjectiveIn this study, patients with suspect COVID-19 symptoms who search for hospital care at the city of Sao Jose do Rio Preto (Sao Paulo, Brazil) were monitored, in order to identify the first case of this new disease in the region. In the first two months (March and April), more than 3000 individuals looked for the public and private health system with suspected respiratory symptoms, but only 164 (8.4%) were COVID-19 confirmed. ResultsFrom those, males (56.1%) and patients of the age distribution of 16-59 (91.2%), with diarrhea (22.2%), runny nose (25%), altered taste (15.9%), and anosmia (11.6%) presented statistical significance, although none comorbidities were related with COVID-19 occurrence. The odds ratio analysis supports this finding. Days of onset of symptoms are positively associated with whit viral load, and the same happens with the occurrence of symptoms (dyspnea and low saturation).

molecular biology↗