Sarcoidosis is a multisystem disease with unknown causes. The prevalence of sarcoidosis that occurs worldwide is highly variable. It is pathologically characterized by the formation of non-necrotizing epithelioid cell granuloma, mainly affecting the respiratory tract and involving extrapulmonary organs including the skin, heart, extrathoracic lymph nodes, central nerves and eyes. A correct diagnosis of sarcoidosis depends on the clinical symptoms, imaging observations, and characteristic histopathological findings. This study aims to review the recent contributions of pulmonary sarcoidosis. It is based on a search of a published article and review on pulmonary sarcoidosis. PubMed, Embase and CNKI were searched for latest developments from 1977. The most common clinical symptoms of sarcoidosis include dry cough, dyspnea, and chest discomfort. The imaging manifestations of sarcoidosis can be divided into typical and atypical findings. Lymphadenopathy is a typical imaging manifestation of sarcoidosis. Sarcoidosis is also a highly variable multisystem disease with an unpredictable clinical course. Clinically encountered cases cover a wide range from asymptomatic patients with incidental findings in radiographic images to chronic progressive diseases. Corticosteroids are the most widely recommended as the first-line treatment for symptomatic or organ-threatening disease in sarcoidosis, but they are associated with substantial toxic effects. Meanwhile, for sarcoidosis, the follow-up is also an important part of the diagnosis and treatment. Pulmonary sarcoidosis needs further recognition. In this paper, the clinical features, imaging observations, pathology, and treatment modalities for pulmonary sarcoidosis are presented and discussed vis-à-vis the current dilemma in diagnosis and therapy.

Aptamers are special types of single-stranded DNA generated by a process called systematic evolution of ligands by exponential enrichment (SELEX). Due to significant advances in the chemical synthesis and biotechnological production, aptamers have gained considerable attention as versatile building blocks for the next generation of soft materials. Hydrogels are high water-retainable materials with a three-dimensional (3D) polymeric network. Aptamers, as a vital element, have greatly expanded the applications of hydrogels. Due to their biocompatibility, selective binding, and molecular recognition, aptamer-based hydrogels can be utilized for bioanalytical and biomedical applications. In this review, we focus on the latest strategies of aptamer-based hydrogels in bioanalytical and biomedical applications. We begin this review with an overview of the underlying design principles for the construction of aptamer-based hydrogels. Next, we will discuss some bioanalytical and biomedical applications of aptamer-based hydrogel including biosensing, target capture and release, logic devices, gene and cancer therapy. Finally, the recent progress of aptamer-based hydrogels is discussed, along with challenges and future perspectives.

Objective: Nocardiosis is a rare opportunistic infection caused by the Nocardia species. Nocardia bacteremia is a life-threatening presentation of disseminated nocardiosis that presents diagnostic and therapeutic challenges. We performed this retrospective analysis in a Chinese hospital from 2010 to 2019 to describe the characteristics of this rare bloodstream infection. Methods: We searched the database of the real-time nosocomial infection surveillance system and identified patients whose blood cultures showed Nocardia bacteria growth. The medical records of these patients were extracted and analyzed by two independent researchers. The data included age, gender, complicating disease, duration from blood drawing to reporting, clinical signs and symptoms, blood routine and C-reactive protein results, radiological examinations, sites of involvement, antibiotic treatments, and outcomes. Results: Seven patients with Nocardia bacteremia were found. There were four male and three female patients, whose ages ranged from 41 to 75 years. Six (85.7%) patients had predisposing conditions and were administrated corticosteroids for various reasons before the identification of Nocardia infection. The most common symptom was fever (100%). Five patients presented with lung or skin involvement; meanwhile, three patients presented with brain involvement. One patient presented with pelvic and peritoneum involvement, respectively. The most common findings of chest CT imaging were consolidation, followed by nodules and cavitations. Trimethoprim/sulfamethoxazole was prescribed to all patients after the diagnosis of Nocardia bacteremia. Six patients recovered, and one patient ultimately died. Conclusions: Nocardia bacteremia is a rare bloodstream infection that usually occurs in immunocompromised patients. Clinical manifestations of patients are nonspecific. It often causes multiple organ involvement, and early diagnosis and prompt aggressive interventions are important to improve the outcome of this disease.

Dihydroartemisinin (DHA), a kind of artemisinin derivatives, has been extensively investigated alone or together with other drugs for anti-cancer therapy in recent years. However, whether a synergistic effect between DHA and cisplatinum (Cis, an anti-cancer drug) existed in treatment of human lung adenocarcinoma is still unknown. This study was designed to explore the potential synergism of DHA and Cis using human lung adenocarcinoma H1299 cells. The cells were treated by DHA, Cis and DHA plus Cis respectively. Untreated cells were used as control. Cell inhibition and apoptosis were evaluated by MTT assays and flow cytometry. The apoptosis associated proteins were assessed by Western blotting and RT-qPCR. Flow cytometry revealed that both DHA and Cis induced significantly H1299 cell apoptosis compared to control group, while a higher apoptotic level was observed in DHA plus Cis treated group. Analysis of apoptotic proteins revealed that caspase-3, -8, -9 were significantly higher in DHA plus Cis treated cells than DHA or Cis alone. Meanwhile, The DHA plus Cis treatment also significantly enhanced caspase-8, -9, -3, -6, -7 and PARP activation compared with DHA or Cis alone, indicating that the caspase-8-related death receptor signaling pathway and the caspase-9-related mitochondrial signaling pathway may play important roles in the synergistic effect of DHA and Cis. In general, this study reveals the obvious synergistic action of the DHA and Cis in inducing apoptosis of H1299 cells via the death receptor and mitochondrial apoptosis pathway.

Lipopolysaccharide (LPS) can activate endothelial cells and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of nuclear factor (NF)-κB. A number of studies have demonstrated the cytoprotective action of perfluorocarbon (PFC) both in vivo and in vitro, but the exact mechanisms have yet to be elucidated. In this study, we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated pulmonary vascular endothelial cells (PMVECs). Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) were significantly increased in the LPS-stimulated PMVECs groups. The expression of TLR-4 mRNA and protein in LPS groups was markedly increased. Meanwhile, NF-κB was activated. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α, and IL-8; the expression of TLR-4 mRNA; and the activity of NF-κB. LPS can induce PMVEC inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect PMVECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway.

BACKGROUND:Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALI and the mechanisms involved.METHODS:MSCs were isolated from male rat bone marrow and the ALI model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo.RESULTS:There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P < 0.05), and myeloperoxidase activity in the lung (P < 0.01), and of TNF-α and IL-1β in serum (P < 0.05) in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-α, IL-1β and macrophage inflammatory protein (MIP)-1α and significantly increased levels of IL-10 (P < 0.05) in the culture supernatants.CONCLUSIONS:Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALI in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.

Objective To investigate the method for isolation and culture of pulmonary microvascular endothelial cells (PMVECs). Methods Primary PMVECs were obtained by complex phosphoesterasum digesting from isolated lung tissues of SD rats. PMVECs were purified by serial subcultivation and identified by morphological characteristics by light microscope, the expression of Ⅷ factor (vWF) detected by immunocytochemical staining, and ultrastructure characteristics under transmission electronic microscopy. Results The primiary PMVECs presented a typical cobblestone morphology and in good condition. vWF was expressed in cytoplasm of the purified cells. Weibel-Palade bodies were shown by transmission electronic microscopy. These features confirmed the cells obtained were PMVECs. Conclusions Methods for isolation and culture of PMVECs by using complex phosphoesterasum digesting in our research can acquire high quantity and viable cells,which maintain the structure and function of PMVECs and can be used in subsequent research.

BACKGROUND:Toll-like receptor-4 (TLR-4) is integrally involved in lipopolysaccharide (LPS) signaling and has a requisite role in the activation of nuclear factor-κB (NF-κB). The exact mechanisms that lend perfluorocarbon (PFC) liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls (AECs).METHODS:AECs (A549 cells, human lung adenocarcinoma cell line) were divided into four groups: control, PFC, LPS and LPS + PFC (coculture group) groups. Intercellular adhesion molecule-1 (ICAM-1) was detected by ELISA, tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting (proteins of I-κBa and NF-κB p65).RESULTS:ICAM-1, TNF-α and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α and IL-8, the expression of TLR-4 mRNA and the activity of NF-κB.CONCLUSIONS:Taken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.

OBJECTIVE Lipopolysaccharide (LPS) can activate alveolar epithelial cells (AECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study is to investigate in an in vitro model the inflammatory responses of AECs induced by LPS and the probable mechanism underlined the observed inflammatory responses. So cytokines of ICAM-1, TNF-α and IL-8 secreted by LPS-activated AECs were observed. And the initial signal molecule (the expression of TLR-4 mRNA) and the key intracellular steps (the activation of NF-κB) were studied in detail. METHODS The study was performed on A549 cells (Human lung adenocarcinoma cell line). A549 cells were divided into two groups: control, and LPS interference group. Proinflammatory cytokines ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detected by real time PCR. The activation of NF-κB was detected by Western blot (proteins of I-κBα and NF-κB p65). RESULTS Compared with control group, ICAM-1 and TNF-α of LPS-stimulated group were significantly higher and peaked after 2h before gradually declining at 6 and 12 h; IL-8 was higher after 2 h, which continued up to 12 h. The expression of TLR-4 mRNA of LPS group was significantly higher and peaked after 2 h and gradually declining at 6 and 12 h. Meanwhile, NF-κB was activated after 0.5, 2, 6 and 12 h indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus approximately synchronized. CONCLUSION Taken together, the results demonstrate that LPS can induce AECs inflammatory injury via activating TLR-4 and subsequently activating NF-κB.

OBJECTIVE Lipopolysaccharide (LPS) can activate pulmonary vascular endothelial cells (PMVECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study was to investigate in an in vitro model the inflammatory responses of PMVECs induced by LPS and the probable mechanism underlying the observed inflammatory responses. METHODS The present study was performed on isolated PMVECs from Sprague-Dawley rats. After being identified, PMVECs were divided into 2 groups: a control group, and a LPS (0.01, 0.1, 1, 10 mg/L) intervention group. ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detected by real time PCR. The activation of NF-κB was detected by Western blot (proteins of I-κBα and NF-κB p65) and immunocytochemical staining (NF-κB p65). RESULTS Compared with the control group, cytokines secreted from PMVECs-stimulated by LPS were increased in a dose-dependent manner. When stimulated with LPS 10 mg/L for 2, 6 and 12 h, cytokines measured were all increased. ICAM-1 and TNF-α were significantly increased and peaked after 2 h before gradually declining at 6 and 12 h. IL-8 was higher after 2 h, which continued up to 12 h. The expression of TLR-4 mRNA was significantly higher and peaked after 2 h and continued to 12 h (4.34 ± 1.42, 3.62 ± 1.45, 3.32 ± 1.36), which were all higher than that of the control group (1.00 ± 0.00, P < 0.05). Meanwhile, NF-κB was activated at 0.5, 2, 6 and 12 h indicated by the significant degradation of IκB-α and the significant increased release of NF-κB P65 and its subsequent translocation into the nucleus with approximately synchronized. CONCLUSION Taken together, the results demonstrated that LPS was able to induce PMVECs inflammatory injury via activating TLR-4 and subsequently activating NF-κB.

Background Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction. This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline. Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR). Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens I and IIIConclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.