Lung cancer remains one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 20%. One approach to improving survival is the identification of biomarkers to detect early stage disease. In this study, we investigated the potential of the stem cell and progenitor cell marker, Musashi1 (Msi1), as a diagnostic marker and potential therapeutic target for lung cancer. Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. Downregulation of Msi1 by lentivirus-mediated expression of an Msi1 shRNA reduced spheroid colony proliferation. Growth inhibition was associated with reduced nuclear localization of β-catenin and inhibition of the processing of intracellular Notch. In primary lung cancer, Msi1 protein expression was elevated in 86% of 202 tissue microarray specimens, and Msi1 mRNA was increased in 80% of 118 bronchoscopic biopsies, including metastatic disease, but was rarely detected in adjacent normal lung tissue and in non-malignant diseased tissue. Msi1 was expressed in a diffuse pattern in most tumor subtypes, except in squamous cell carcinomas, where it appeared in a focal pattern in 50% of specimens. Thus, Msi1 is a sensitive and specific diagnostic marker for all lung cancer subtypes.

BackgroundPrevious reports have suggested that malignant transformations originate from adult stem cells, and may thus express the stem-cell-associated markers. The purpose of this study is to investigate the differential expression and clinical significance of seven stem-cell-associated markers (Bmi1, CD133, CD44, Sox2, Nanog, OCT4 and Msi2) in lung cancer, providing new targets for the diagnosis and treatment of lung cancer.MethodsIn this study, we evaluated the differential expression of mRNA levels seven stem-cell-associated markers by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) from 112 human lung cancer and 18 non-cancer tissues obtained by bronchoscopy. We further verified the differential expression of these markers by immunohistochemistry in 50 lung cancer specimens, 30 benign inflammatory lesion tissues and 20 non-tumor adjacent lung tissues.ResultsWith the exception of OCT4, other markers Bmi1, CD133, CD44, Sox2, Nanog and Msi2 mRNA and protein were abundantly expressed in lung cancer. Additionally, Nanog expression was highly upregulated in lung cancer tissues and rarely presented in non-cancerous lung tissues, the sensitivity and specificity of Nanog mRNA reached 63.4% and 66.7%, respectively. Nanog therefore possessed high diagnostic value, however, CD44, Bmi1 and CD133 showed poor diagnostic value in lung cancer.ConclusionNanog may serve as a promising diagnostic marker of lung cancer and potential therapeutic target in lung cancer.

Background. Upper respiratory tract infections (URTIs) are common and burdensome infectious illness. Several trials have reported that probiotics can prevent URTIs in adults. Objectives. To evaluate the efficacy and safety of probiotics in the prevention of URTIs in adults. Methods. PubMed, Web of Science, Embase, and Cochrane Library were searched for reports published from database inception to May 14, 2020. Randomized controlled trials (RCTs) comparing probiotics with placebo for the prevention of URTIs in adults were included. Results. Six RCTs with 1551 participants were included. Compared with the placebo group, the probiotics intervention group significantly reduced the incidence of URTI episodes (RR: 0.77; 95% CI: 0.68 to 0.87; P < 0.0001 ; I2 = 26%), the episode rate of URTIs (rate ratio: 0.72; 95% CI: 0.60 to 0.86; P = 0.0002 ; I2 = 99%), and the mean duration of one episode of URTI (MD: −2.66; 95% CI: −4.79 to −0.54; P = 0.01 ; I2 = 80%). The adverse events of probiotics were mainly mild gastrointestinal symptoms. There were no significant differences in occurrence rate of adverse effects between probiotics intervention and placebo group (rate ratio: 1.01; 95% CI: 0.80 to 1.26; P = 0.96 ; I2 = 99%). Conclusion. Low-quality evidence provides support that probiotics have potential efficacy for preventing URTI episodes in adults. More trials are required to confirm this conclusion.

Purpose The Hippo signaling pathway participates in the restriction of cell proliferation and organ growth. Activated macrophages have been implicated in the pathogenesis of allergic asthma. Recent studies have shown that Hippo signaling pathway may also be involved in the regulation of asthma. However, the link between Hippo signaling pathway and macrophages in the context of allergic asthma has not been investigated. The purpose of this study was to explore the link between Hippo signaling pathway and macrophages using a mice model of OVA-induced allergic asthma. Methods Mice models of asthma were established. Lung tissues were collected from mice and pooled for mRNA sequencing and bioinformatics analysis. The relative mRNA expression of Hippo signalling pathway-related proteins Yap1, Lef1 and Ctgf was also measured. Double immunofluorescence staining was performed on lung tissues to evaluate macrophage marker F4/80 expression and Yap1/Lef1/Ctgf expression. Results Results of the RNA-Seq of lung tissues demonstrated that the Hippo signaling pathway was down-regulated in OVA-induced allergic asthma. Using the cytoHubba tool kits in Cytoscape, the following top 10 hub genes of Hippo signalling pathway were identified: Yap1, Lef1, Ctgf, Ccnd1, Axin2, Smad7, Wnt4, Wnt3a, Pard6b, and Wwc1 . Using the seq-ImmuCC ( http://218.4.234.74:3200/immune/ ), a negative correlation was found between macrophages and Hippo signaling pathway activity (R 2 = 0.93). The mRNA expression levels of pulmonary Yap1, Lef1, and Ctgf were down-regulated in the mice model of OVA-induced allergic asthma. Moreover, double-stained immunofluorescence for F4/80 and Yap1, Lef1, Ctgf in mouse lung sections respectively revealed that macrophage proliferation was correlated with downregulation of the Hippo signaling pathway in the mice model of OVA-induced allergic asthma. Conclusion These results demonstrated that the Hippo signaling pathway was down-regulated in asthma mice, and the proliferation of macrophages was associated with downregulation of the Hippo signaling pathway. These findings reveal novel insights into the pathogenesis and treatment of asthma.

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Scrub typhus is often misdiagnosed in febrile patients, leading to antibiotic abuse and multiple complications. We conducted a retrospective record review at the Fourth Affiliated Hospital of Guangxi Medical University in China. Data were collected on 52 patients with a confirmed diagnosis of scrub typhus and complete clinical data. In addition, data were collected on 52 patients with bloodstream infection, 25 patients with HIV infection, 112 patients with common community-acquired pneumonia (CCAP), and 36 patients with severe community-acquired pneumonia (SCAP) to serve as control groups. The peripheral blood CD4 and CD8 counts, CD4/CD8 ratio, C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, and β2 microglobulin levels; and the white blood cell count and neutrophil percentage were compared between the scrub typhus and the control groups. The value of these biomarkers in the diagnosis of scrub typhus was assessed using receiver–operating characteristic curve analysis. The scrub typhus group had a significantly lower CD4 count and CD4/CD8 ratio than the bloodstream infection, CCAP, and SCAP groups, and a significantly greater CD4 count and CD4/CD8 ratio than the HIV infection group. In contrast, the scrub typhus group had a significantly greater CD8 count than the bloodstream infection and CCAP and SCAP groups, and it had a lower level of CD8 than the HIV infection group. The areas under the curve of CD4/CD8 were more than 0.93 in the receiver–operating characteristic curve analysis. These findings suggest that the CD4/CD8 ratio is a useful ancillary test for diagnosing scrub typhus.

Epidemiological studies have shown that exposure to beneficial microorganisms can reduce the risk of asthma, but the clinical use of live probiotics is controversial due to the risk of infection. As heat-killed probiotics can also exhibit immunomodulatory activity, this study is aimed at investigating whether heat-killed Clostridium butyricum (HKCB) CGMCC0313-1 could reduce allergic airway inflammation in an ovalbumin-induced mouse model. Mice received aerosol inhalation of HKCB, oral administration of HKCB, or oral administration of live Clostridium butyricum (CB) during sensitization. Bronchoalveolar lavage fluid cell number, histology, and levels of the cytokines interferon-gamma and IL-4, the autophagy-related proteins LC3B, Beclin1, and p62, and members of the nuclear factor kappa B (NF-κB)/NLRP3 inflammasome signaling pathway were examined. Our results demonstrated that aerosol inhalation of HKCB, oral HKCB administration, and oral live CB administration alleviated allergic airway inflammation and mucus secretion in allergic mice. Aerosol inhalation of HKCB was the most effective method; it restored the Th1/Th2 balance, ameliorated autophagy, and inhibited the NF-κB/NLRP3 inflammasome signaling pathway in the lungs of allergic mice. Thus, aerosol inhalation of HKCB could be a promising strategy for the prevention or treatment of asthma.