Summary Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4 − CD8 − unconventional αβ T cells (UTC αβ ). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTC αβ associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTC αβ polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.
Objective: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. Study Design and Setting: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Results: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan–Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). Conclusion: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.
Public health endorsements during the present COVID-19 pandemic has led the governments of largely affected countries to imply policies that restrict social mobility to slow COVID-19 spread. The study aimed to explore the effects of COVID-19 home quarantine on lifestyle and health behavior of Saudi residents. An online survey in Saudi Arabia was launched from May 11 to June 6, 2020. The survey was designed by multidisciplinary scientists and academics uploaded and shared through the Google platform in Arabic and English languages. Questions presented related to responses “before” and “during” COVID-19 home quarantine. A total of 1965 respondents participated and were included in the analysis [921 (47.0%) males and 1044 (53.0%) females]. Non-Saudis were more likely to increase their physical activity during quarantine [odds ratio (95% confidence interval 1.41 (1.11–1.79); p < 0.005]. Prevalence of participants walking daily for more than 4 times per week significantly decreased during pandemic (before vs during, 30.5% vs 29.1%) which was in parallel to the significant increase in the prevalence of participants who did not perform daily walking during the quarantine (21% vs 22.9%; p < 0.001). The prevalence of participants who often consume snacks between meals increased during quarantine (27.4% vs 29.4%, p < 0.001), while the prevalence of participants who never consumed fresh fruits and vegetables significantly increased during home quarantine (2.4% vs 3.7%; p = 0.019). The lockdown imposed in Saudi Arabia modestly but significantly impacted physical activity and dietary behaviors of several citizens and residents in an unhealthy way. Interventions to alleviate these acute adverse lifestyle behaviors during pandemic should be formulated.
Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells – particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the “browning” of white fat depots through recruitment of UCP1 and the development of brite adipocytes.
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