The causal role of gut microbiota in susceptibility and severity of COVID-19: A bidirectional Mendelian randomization study.

Growing evidence has shown that altered gut microbiota is associated with the pathogenesis of COVID-19, but their causal effects are still unclear. We conducted a bidirectional Mendelian randomization (MR) study to assess the causal effects of gut microbiota on COVID-19 susceptibility or severity, and vice versa. The microbiome genome-wide association studies (GWAS) data of 18 340 individuals and GWAS statistics from the COVID-19 host genetics initiative (38 984 European patients and 1 644 784 controls) were used as exposure and outcomes. The inverse variance weighted (IVW) was used as the primary MR analysis. Sensitivity analyses were performed to validate the robustness, pleiotropy, and heterogeneity of results. In the forward MR, we identified several microbial genera with causal effects on COVID-19 susceptibility (p < 0.05 and FDR < 0.1): Alloprevotella (odds ratio [OR]: 1.088, 95% confidence interval [CI]: 1.021-1.160), Coprococcus (OR: 1.159, 95% CI: 1.030-1.304), Parasutterella (OR: 0.902, 95% CI: 0.836-0.973), and Ruminococcaceae UCG014 (OR: 0.878, 95% CI: 0.777-0.992). The Reverse MR identified that exposure to COVID-19 had causal effects on the depletion of the families Lactobacillaceae (Beta [SE]: -0.220 [0.101]) and Lachnospiraceae (-0.129 [0.062]), the genera Flavonifractor (-0.180 [0.081]) and Lachnoclostridium [-0.181 [0.063]). Our findings supported the causal effect of gut microbiota on the pathogenesis of COVID-19, and infection of COVID-19 might further causally induce gut microbiota dysbiosis.

Naringenin inhibits allergen-induced airway inflammation and airway responsiveness and inhibits NF-kappaB activity in a murine model of asthma.

Naringenin, a flavonoid, has antiinflammatory and immunomodulatory properties. We investigated whether naringenin could attenuate allergen-induced airway inflammation and its possible mechanism in a murine model of asthma. Mice were sensitized and challenged with ovalbumin. Some mice were administered with naringenin before ovalbumin challenge. We evaluated the development of airway inflammation and airway reactivity. Interleukin (IL)4, IL13, chemokine (C-C motif) ligand (CCL)5, and CCL11 in bronchoalveolar lavage fluid and serum total IgE were detected by ELISA. IkappaBalpha degradation and inducible nitric oxide synthase (iNOS) in lungs were measured by Western blot. We also tested NF-kappaB binding activity by electrophoretic mobility shift assay. The mRNA levels of iNOS, CCL5, and CCL11 were detected by real-time PCR. Naringenin attenuated ovalbumin-induced airway inflammation and airway reactivity in experimental mice. The naringenin-treated mice had lower levels of IL4 and IL13 in the bronchoalveolar lavage fluid and lower serum total IgE. Furthermore, naringenin inhibited pulmonary IkappaBalpha degradation and NF-kappaB DNA-binding activity. The levels of CCL5, CCL11, and iNOS were also significantly reduced. The results indicated that naringenin may play protective roles in the asthma process. The inhibition of NF-kappaB and the decreased expression of its target genes may account for this phenomenon.

[Impulse oscillometry for estimation of airway obstruction].

OBJECTIVE: To explore the application of impulse oscillometry (IOS) in the estimation of airway obstruction and to evaluate the correlation between spirometry indices and IOS parameters. METHODS: From Nov.2007 to May 2008, spirometry and IOS measurements were performed in 100 participants (male 72, female 28). FEV(1), FVC, FEV(1)/FVC, airway resistance at 5 Hz (R(5)), airway resistance at 20 Hz (R(20)), central resistance (Rc) and peripheral resistance (Rp) of structural parameters interpretation graph, FEV(1)% pred, R(5)% pred, R(20)% pred, and FEV(1)/FVC were analyzed. Correlations between spirometry and IOS parameters were studied. RESULTS: All participants had satisfactory impulse oscillometry results. R(5) and Rp were significantly increased in FEV(1)/FVC < 70% group [(5.3 +/- 2.1) and (6.2 +/- 2.9) cm H(2)OxL(-1)xs(-1) (1 cm H2O = 0.098 kPa)], respectively. There was significant negative correlation between FEV(1) and R(5) and Rp (correlation coefficient was -0.38 and -0.47 respectively, all P < 0.01). There was also negative correlation between FVC and R(5) and Rp (correlation coefficient was -0.28 and -0.37, respectively, all P < 0.01). A significant negative correlation between FEV(1)% pred, FVC% pred, FEV(1)/FVC% pred and R(5)% pred was also observed (correlation coefficient -0.49, -0.39 and -0.43, respectively). CONCLUSIONS: IOS parameters can be used to evaluate airway obstruction. Among IOS parameters, R(5) was the most sensitive, which was also significantly correlated with spirometric parameters.

Glomus tumors of the trachea: 2 case reports and a review of the literature.

Glomus tumors (GTs) of the trachea are very rare neoplasms that usually arise from the distal portion of the respiratory tree. The origin of these tumors is modified smooth muscle cells of glomus bodies. In this study, we describe two cases of GT of the trachea, as well as the histologic features of these tumors and their treatments. One tumor was diagnosed via bronchoscopic biopsy, and the other tumor was diagnosed via surgery. Clinical follow-up showed that the two patients are alive and well after 8 and 15 months post-treatment, respectively. We also review the literature regarding GTs and discuss the clinical presentation, histologic features, differential diagnosis, treatment and prognosis of these tumors.

Chronic asthma results in cognitive dysfunction in immature mice.

Asthma is the most common chronic childhood illness today. However, little attention is paid for the impacts of chronic asthma-induced hypoxia on cognitive function in children. The present study used immature mice to establish ovalbumin-induced chronic asthma model, and found that chronic asthma impaired learning and memory ability in Morris Water Maze test. Further study revealed that chronic asthma destroyed synaptic structure, impaired long-term potentiation (LTP) maintaining in the CA1 region of mouse hippocampal slices. We found that intermittent hypoxia during chronic asthma resulted in down-regulation of c-fos, Arc and neurogenesis, which was responsible for the impairment of learning and memory in immature mice. Moreover, our results showed that budesonide treatment alone was inadequate for attenuating chronic asthma-induced cognitive impairment. Therefore, our findings indicate that chronic asthma might result in cognitive dysfunction in children, and more attention should be paid for chronic asthma-induced brain damage in the clinical therapy.