The SARS-CoV-2 infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates the severe cases of COVID-19. Here, we reported that SARS-CoV-2 induces upregulation and activation of human Caspase-4/CASP4 (mouse Caspase-11/CASP11), and this process contributes to NLRP3 activation. In vivo infections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11–/– mice were protected from disease development, with the increased pulmonary parenchymal area, reduced clinical score of the disease, and reduced mortality. Assessing human samples from fatal cases of COVID-19, we found that CASP4 was expressed in patient lungs and correlated with the expression of inflammasome components and inflammatory mediators, including CASP1, IL1B, IL18, and IL6. Collectively, our data establish that CASP4/11 promotes NLRP3 activation and disease pathology, revealing a possible target for therapeutic interventions to COVID-19.
Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment. Keywords: COVID-19, C5aR1, C5a, SARS-CoV-2, Myeloid cells, Neutrophils, NETs
This study evaluated the serum cortisol response to a single session of whole-body vibration (WBV) in healthy adult dogs. Ten healthy adult medium dogs, females and males, aged between 24 and 48 months and with body weight between 10.1 and 17.9 kg were used. A single WBV session at a frequency of 30 Hz for 5 min (3.10 mm peak displacement, 11.16 m/s2 peak acceleration, and 0.29 m/s velocity), then 50 Hz for 5 min (3.98 mm peak displacement, 39.75 m/s2 peak acceleration, and 0.62 m/s velocity), and finishing with 30 Hz for 5 min (3.10 mm peak displacement, 11.16 m/s2 peak acceleration, and 0.29 m/s velocity) was performed. Serum cortisol, heart and respiratory rate, and systolic blood pressure were evaluated at different time points: 1 min before WBV (1PRE) and 1 min (1POST), 60 min (60POST), and 360 min (360POST) after the WBV session. An increase (P = 0.0417) of the serum cortisol values was observed between 1PRE and 1POST and a decrease (P = 0.0417) between 1POST and 60POST and between 60POST and 360POST. However, the values remained within the reference range. The heart and respiratory rate and the systolic blood pressure remained unchanged. Our findings suggest that a single bout of WBV (5 min of 30 and 50 Hz) using a vibrating platform that delivered a vortex wave circulation does not modify the serum cortisol levels and clinical parameters of healthy adult dogs.
As vibrações de corpo inteiro são geradas por dispositivoscapazes de gerar oscilações - plataformas vibratórias. Diversosbenefícios do uso de plataformas vibratórias têm sido descritos,como aumento da força muscular, melhora do desempenhofísico e melhora do equilíbrio e da mobilidade funcional. Avibração de corpo inteiro tem sido estudada e usada em muitasaplicações em seres humanos, existindo apenas alguns estudospublicados sobre vibração de corpo inteiro como modalidadeterapêutica em animais. A presente revisão teve como objetivoresumir os resultados de artigos originais que investigaramos efeitos da vibração de corpo inteiro em animais. Foramutilizados artigos publicados em revistas internacionais emMedicina Veterinária, e foram incluídos pequenos animais,animais de grande porte e animais silvestres. Poucos estudosrelacionados ao uso da vibração de corpo inteiro foramidentificados e as publicações sobre animais silvestres foramescassas. O uso de parâmetros de vibração errados, incluindoa intensidade de vibração, tempo de exposição, amplitude eaceleração, também causa efeitos adversos em animais. Mais estudos são necessários para determinar um protocolo adequado e a eficácia da vibração de corpo inteiro em cada espécie, como também para explorar outras aplicações terapêuticas.Descritores: Plataforma vibratória; Vibrações mecânicas; Veterinária.
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