When COVID-19 sits on people's laps: A systematic review of SARS-CoV-2 infection prevalence in household dogs and cats.

During the COVID-19 pandemic, questions were raised about whether SARS-CoV-2 can infect pets and the potential risks posed to and by their human owners. We performed a systematic review of studies on SARS-CoV-2 infection prevalence in naturally infected household dogs and cats conducted worldwide and published before January 2022. Data on SARS-CoV-2 infection prevalence, as determined by either molecular or serological methods, and accompanying information, were summarized. Screening studies targeting the general dog or cat populations were differentiated from those targeting households with known COVID-19-positive people. Studies focusing on stray, sheltered or working animals were excluded. In total, 17 studies were included in this review. Fourteen studies investigated cats, 13 investigated dogs, and 10 investigated both. Five studies reported molecular prevalence, 16 reported seroprevalence, and four reported both. All but two studies started and ended in 2020. Studies were conducted in eight European countries (Italy, France, Spain, Croatia, Germany, the Netherlands, UK, Poland), three Asian countries (Iran, Japan, China) and the USA. Both molecular and serological prevalence in the general pet population were usually below 5%, but exceeded 10% when COVID-19 positive people were known to be present in the household. A meta-analysis provided pooled seroprevalence estimates in the general pet population: 2.75% (95% Confidence Interval [CI]: 1.56-4.79%) and 0.82% (95% CI: 0.26-2.54%) for cats and dogs, respectively. This review highlighted the need for a better understanding of the possible epizootic implications of the COVID-19 pandemic, as well as the need for global standards for SARS-CoV-2 detection in pets.

Characterising the gut microbiome of stranded harbour seals (Phoca vitulina) in rehabilitation.

Animal rehabilitation centres provide a unique opportunity to study the microbiome of wild animals because subjects will be handled for their treatment and can therefore be sampled longitudinally. However, rehabilitation may have unintended consequences on the animals' microbiome because of a less varied and suboptimal diet, possible medical treatment and exposure to a different environment and human handlers. Our study describes the gut microbiome of two large seal cohorts, 50 pups (0-30 days old at arrival) and 23 weaners (more than 60 days old at arrival) of stranded harbour seals admitted for rehabilitation at the Sealcentre Pieterburen in the Netherlands, and the effect of rehabilitation on it. Faecal samples were collected from all seals at arrival, two times during rehabilitation and before release. Only seals that did not receive antimicrobial treatment were included in the study. The average time in rehabilitation was 95 days for the pups and 63 days for the weaners. We observed that during rehabilitation, there was an increase in the relative abundance of some of the Campylobacterota spp and Actinobacteriota spp. The alpha diversity of the pups' microbiome increased significantly during their rehabilitation (p-value <0.05), while there were no significant changes in alpha diversity over time for weaners. We hypothesize that aging is the main reason for the observed changes in the pups' microbiome. At release, the sex of a seal pup was significantly associated with the microbiome's alpha (i.e., Shannon diversity was higher for male pups, p-value <0.001) and beta diversity (p-value 0.001). For weaners, variation in the microbiome composition (beta diversity) at release was partly explained by sex and age of the seal (p-values 0.002 and 0.003 respectively). We mainly observed variables known to change the gut microbiome composition (e.g., age and sex) and conclude that rehabilitation in itself had only minor effects on the gut microbiome of seal pups and seal weaners.

Suppression of radiation-induced migration of non-small cell lung cancer through inhibition of Nrf2-Notch Axis.

Nuclear factor E2 related factor 2 (Nrf2) is a transcription factor that is associated with tumor growth and resistance to radiation. The canonical Notch signaling pathway is also crucial for maintaining non-small cell lung cancer (NSCLC). Aberrant Nrf2 and Notch signaling has repeatedly been showed to facilitate metastasis of NSCLC. Here, we show that radiation induce Nrf2 and Notch1 expression in NSCLC. Knockdown of Nrf2 enhanced radiosensitivity of NSCLC and reduced epithelial-to-mesenchymal transition. Importantly, we found that knockdown of Nrf2 dramatically decreased radiation-induced NSCLC invasion and significantly increased E-cadherin, but reduced N-cadherin and matrix metalloproteinase (MMP)-2/9 expression. We found that Notch1 knockdown also upregulated E-cadherin and suppressed N-cadherin expression. Nrf2 contributes to NSCLC cell metastatic properties and this inhibition correlated with reduced Notch1 expression. These results establish that Nrf2 and Notch1 downregulation synergistically inhibit radiation-induced migratory and invasive properties of NSCLC cells.

Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells.

The nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant system. Nrf2 is often constitutively activated in non-small cell lung cancer (NSCLC) cell lines, which promotes cytoprotection against oxidative stress and xenobiotics. Notch1 signaling is critically implicated in cell fate determination. It has been reported that Nf2 strongly regulates Notch1 activity. However, the role of Nrf2 mediated Notch1 signaling in response to ionizing radiation (IR) remains elusive. We report that knockdown of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch1 signaling in NSCLC cells. IR activated Nrf2 in a dose-dependent manner and the expression of Nrf2 was significantly elevated at 4 h after exposure. RNAi-mediated reduction of Nrf2 significantly increased endogenous ROS levels, and decreased the expression of glutamate cysteine ligase catalytic subunit (GCLC), heme oxygenase-1 (HO-1) and NAD (P) H quinine oxidoreductase-1 (NQO1) in irradiated cells. Furthermore, decrease in Nrf2 expression significantly dampened Notch1 expression following ionizing radiation exposure, and potentiated IR-induced cellular apoptosis. These results demonstrated that Nrf2 could be activated by ionizing radiation, knockdown of Nrf2 could promote radiation induced apoptosis and Nrf2-mediated Notch signaling is an important determinant in radioresistance of lung cancer cells.