A novel variant of Chlamydia psittaci causing human psittacosis in China.

From January 2022 to November 2022, sporadic psittacosis occurred in Lishui city, China. The patients were presented with fever, cough, and pulmonary infiltration. Their clinical symptoms were not relieved after receiving cephalosporin, penicillin, beta-lactamase inhibitors, and quinolones. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples from the patients revealed Chlamydia psittaci infection. Then, three C. psittaci strains were isolated from the patients. Their whole genome sequences (WGSs) were obtained, and a core genome multilocus sequence typing (cgMLST) method was developed to study the population structure of C. psittaci. Using the constructed cgMLST method, 72 WGSs were divided into four related groups and ten sub-clusters. The Lishui strains formed a unique population of C. psittaci, which might represent a new variant of C. psittaci. In vitro antimicrobial susceptibility testing suggested that the Lishui strains were sensitive to tetracycline, macrolides, quinolones, and no drug-resistance was observed.

Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin.

OBJECTIVES: Reportedly, ganoderic acid A (GA-A) increases the sensitivity of hepatocellular carcinoma cells to cisplatin (DDP) chemotherapy. Therefore, this study aims to fathom the influence of GA-A on lung cancer cells. METHODS: After the construction of A549/DDP cells through exposure to DDP, the effects of GA-A on A549 and A549/DDP cells were revealed by cellular functional assays, western blot and quantitative reverse transcription PCR (qRT-PCR). The DDP-resistant lung cancer tumor was established in vivo, followed by further validation of the mechanism of GA-A. RESULTS: GA-A suppressed the viability, migration, and invasion while downregulating Beclin and autophagy marker LC3II/LC3I levels and upregulating P62 levels in A549 and A549/DDP cells. These effects were reversed by circFLNA overexpression. Also, GA-A reinforced the sensitivity of A549/DDP cells to DDP, elevated the apoptosis and regulated the circFLNA/miR-486-3p/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/X-ray repair cross-complementing 1 (XRCC1) axis. The reversal effects of circFLNA overexpression on GA-A-induced viability and apoptosis of A549/DDP cells could all be counteracted in the presence of 3MA. GA-A inhibited lung cancer tumor growth and blocked autophagy. CONCLUSION: GA-A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to DDP.

Luteolin suppresses lung cancer progression through targeting the circ_0000190/miR-130a-3p/notch-1 signaling pathway.

Lung cancer is the leading cause of cancer mortality worldwide. Luteolin has been reported to repress the development of lung cancer. And circular RNAs (circRNAs) circ_0000190 was upregulated in lung cancer tissues. This study is designed to explore the roles of luteolin and circ_0000190 in lung cancer progression. Cell viability, colony number, migration, invasion, and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. The lactate dehydrogenase (LDH) release was determined by special kits. Protein levels of B-celllymphoma-2 (Bcl-2) Cleaved-caspase3 (casp3), Bcl-2 related X protein (Bax), Notch-1, hairy enhance of split-1(Hes-1), and vascular endothelium growth factor (VEGF) were determined by western blot assay. Circ_0000190 andmicroRNA-130a-3p (miR-130a-3p) expression were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The binding relationship between circ_0000190 andmiR-130a-3pwas predicted by starbase and then verified by a dual-luciferase reporter and RNA pull-down assays. The biological roles of Luteolin and circ_0000190 on tumor growth of lung cancer were examined by the xenograft tumor model in vivo. Luteolin inhibited cell viability, colony formation, migration, invasion, and promoted apoptosis of lung cancer cells. Moreover, overexpression of circ_0000190 could counteract the suppression role of luteolin on lung cancer development. Andcirc_0000190 directly bound with miR-130a-3p. Luteolin blocked lung cancer cell growth, metastasis, and Notch-1 signaling pathway by modulating the circ_0000190/miR-130a-3pin vitro. Luteolin repressed tumor growth of lung cancer in vivo by regulating circ_0000190. Luteolin dampened the progression of lung cancer partly by regulating circ_0000190/miR-130a-3p, providing an underlying therapeutic target for lung cancer.

Inhibitory Effect of Immunologically Activated Mesenchymal Stem Cells on Lung Cancer Cell Growth and Metastasis.

Background: Mesenchymal stem cells (MSCs) could inhibit the proliferation of lung cancer cells. The authors' study investigated the effects of immunologically activated human umbilical cord (HUC)-MSCs on A549 lung cancer cells. Materials and Methods: HUC-MSCs were separated from the umbilical cord using the adherence method. Surface markers of HUC-MSCs were detected by flow cytometry for MSC identification. Imiquimod (TLR7 agonist) was incubated with HUC-MSCs for immune activation, and the expression of MSC-specific markers and immune inflammatory molecules was measured by quantitative real-time polymerase chain reaction. HUC A549 cells were cocultured with HUC-MSCs treated with imiquimod, siTLR7 (small interfering RNA for TLR7) or TLR7 overexpression, and then cell viability, proliferation, migration, and invasion, and the expression of phosphatidylinositol-3-kinase (PI3K)/Akt and NF-κB was investigated using MTT assay, clone formation assay, transwell assay, and Western blot, respectively. Results: HUC-MSCs were identified as positive for CD73, CD105, CD44, CD29, and CD90. Expression of MSC markers was inhibited, while those of immune inflammatory molecules expression except IL-6 (interleukin-6) was enhanced after MSCs were immunologically activated by imiquimod. After being cocultured with HUC-MSCs treated with imiquimod or overexpressed TLR7, cell viability, proliferation, and metastasis, and the phosphorylation of P65 and AKT in A549 cells were decreased, but apoptosis was increased, while siTLR7 showed the opposite effect HUC. Conclusions: Immunologically activated HUC-MSCs inhibited the growth and metastasis, yet, promoted the apoptosis of A549 lung cancer cells via regulating the PI3K/Akt and NF-κB pathways.

Severe community-acquired pneumonia caused by Chlamydia psittaci genotype E/B strain circulating among geese in Lishui city, Zhejiang province, China.

Between November 2021 and January 2022, four patients of community-acquired pneumonia were admitted to the hospitals in Lishui city, Zhejiang province, China. Their main clinical manifestations were fever and dry cough as well as radiographic infiltrate, but the empiric antimicrobial therapy or traditional Chinese medicine was not effective for their illness. Clinical specimens from the patients as well as environmental and poultry specimens were collected for the determination of the causative pathogen. The ompA gene and seven housekeeping genes of Chlamydia psittaci were successfully amplified from all the patients, and the sequences of each gene were identical to one another, suggesting that they were infected by the same strain of C. psittaci. A novel strain of C. psittaci (LS strain) was isolated from the bronchoalveolar lavage fluid of patient 2 and its whole genome was obtained. Phylogenetic analyses based on the whole-genome sequences showed that the isolate is most closely related to the strain (WS/RT/E30) identified as genotype E/B. In addition, The ompA gene and four housekeeping genes of C. psittaci were also amplified from two of four faeces samples of geese at the home of patient 2, and the sequences from geese were 100% identical to those from the patients. Accordingly, these cases could be attributed to a circulating C. psittaci strain of genotype E/B in the local geese. Therefore, there is an urgent need to strengthen the regional surveillance on C. psittaci among poultry and humans for prevention and control of the outbreak of psittacosis in the city.

IL-10/IL-10 receptor 1 pathway promotes the viability and collagen synthesis of pulmonary fibroblasts originated from interstitial pneumonia tissues.

Interstitial pneumonia is a pulmonary interstitial inflammatory and fibrosis disease with a variety of causes that causes respiratory disorders and threatens the lives of patients. The present study aimed to investigate the expression of interleukin (IL)-10 in peripheral blood of patients with interstitial pneumonia and its biological functions in pulmonary fibroblasts. A total of 42 patients with idiopathic pulmonary fibrosis (IPF) and 20 healthy subjects were included. ELISA was used to determine IL-10 concentration in serum from the patients and healthy subjects. Primary fibroblasts were isolated from lung tissue successfully and determined by morphology. The CCK-8 assay was performed to determine the effect of IL-10 expression on cell viability. Western blotting was used to determine COL1a1, COL1a2 and IL-10R1 protein expression. Flow cytometry was used for cell cycle analysis and to determine the number of IL-10+ cells. Expression of IL-10 in serum from IPF patients was higher compared to that from healthy subjects. IL-10 promoted the viability and collagen synthesis and secretion of MRC-5 cells and primary pulmonary fibroblasts. IL-10 and IL-10 receptor (R) 1 served regulatory roles in the viability and collagen synthesis of MRC-5 cells. The ratio of peripheral mononuclear lymphocytes with positive expression of IL-10 was elevated in peripheral blood from patients with IPF. The present study demonstrated that IL-10 expression in peripheral blood of patients with IPF is increased significantly compared with healthy subjects. Activation of the IL-10/IL-10R1 signaling pathway promoted the viability and collagen synthesis and secretion of pulmonary fibroblasts, leading to pulmonary fibrosis. The present study provided experimental basis for further understanding the development mechanism of pulmonary fibrosis.

Baicalin attenuates XRCC1-mediated DNA repair to enhance the sensitivity of lung cancer cells to cisplatin.

Baicalin plays important roles in different types of cancer. A previous report showed that baicalin attenuates cisplatin resistance in lung cancer. However, its mechanism remains unclear. In this study, we investigated the effect and mechanism of baicalin on DNA repair and sensitivity of lung cancer cells to cisplatin. A549 and A549/DPP cells were treated with baicalin and cisplatin. A549/DPP cells were transfected with XRCC1 and siXRCC1. Cell viability and DNA damage were detected by MTT and comet assay. Apoptosis rate and cell cycle were detected by flow cytometry assay. The expressions of Bax, Bcl-2, and Cyclin D1 were detected by western blot. XRCC1 expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Baicalin and cisplatin decreased cell viability in A549 and A549/DPP cells in dose-dependent manner. Baicalin enhanced the effect of cisplatin on promoting apoptosis, arresting cell on S stage and triggering DNA damage accompanied with the upregulation of Bcl-2-associated X protein (Bax) and downregulation of B-cell lymphoma 2 (Bcl-2) and Cyclin D1 in A549/DPP cells. Moreover, baicalin promoted the inhibitory effect of cisplatin on XRCC1 expression in A549 and A549/DPP cells. However, the synthetic effects of baicalin and cisplatin on A549/DPP cells were partially inhibited by XRCC1 overexpression and promoted by XRCC1 knockdown. This study demonstrates that baicalin interferes with XRCC1-mediated cellar DNA repair to sensitize lung cancer cells to cisplatin.

Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1.

Significantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis.

OBJECTIVE: The aim of the present work was to investigate the clinical efficacy of first-line chemotherapy regimens in the treatment of advanced non-small cell lung cancer (NSCLC) through a comprehensive network meta-analysis (NMA). METHODS: The prospective randomized controlled clinical trials relevant to 10 first-line chemotherapy regimens in the treatment of advanced NSCLC were systematic electronic search in the databases of Pubmed, Embase, Cochrane Library and CNKI. The combined direct or indirect objective response rate (ORR) between each of the 10 first-line chemotherapy regimens was calculated. RESULTS: Seventeen prospective clinical trials of first-line chemotherapy regimens in treatment of advanced NSCLC were included in the NMA. The 10 treatment regimens including A = cisplatin + gemcitabine, B = carboplatin + gemcitabine, C = gemcitabine, D = carboplatin + paclitaxel, E = paclitaxel + gemcitabine, F = docetaxel + carboplatin, G = gemcitabine + vinorelbine, H = pemetrexed + carboplatin, I = cisplatin + pemetrexed and J = cisplatin + docetaxel were compared in the present NMA. Direct pooled results indicated that the ORR was not statistically different (P all > 0.05). However, NMA showed that the combined ORR for regimens A (OR = 1.47, 95% CI: 0.80-2.81), B (OR = 3.22, 95% CI: 1.45-6.923), D (OR = 3.30, 95% CI: 1.22-9.33), E (OR = 4.36, 95% CI: 1.64-12.82), G (OR = 3.72, 95% CI: 1.12-12.83) and I (OR = 5.80, 95% CI: 2.04-17.86) was superior to regimen C. Rank probability analysis indicated that regimen C = gemcitabine and regimen I = cisplatin + pemetrexed had the highest probability of inferior and superior treatment ORR among the 10 first-line chemotherapy regimens. CONCLUSION: Cisplatin + pemetrexed may have particularly prominent ORR for advanced NSCLC as the first-line chemotherapy regimen.