- Hydrocortisone Promotes Differentiation of Mouse Embryonic Stem Cell-Derived Definitive Endoderm toward Lung Alveolar Epithelial Cells. [Journal Article]
- CJCell J 2019; 20(4):469-476
- CONCLUSIONS: These results suggest that hydrocortisone can be a promoting factor in alveolar fate differentiation of IDE2-induced mESC-DE cells. These cells have potential for drug screening and cell-replacement therapies.
- Afatinib-induced Interstitial Lung Disease Successfully Treated with Corticosteroids: Case Report and Review of the Literature. [Journal Article]
- CCureus 2018 Jun 14; 10(6):e2805
- The first-line treatment for advanced epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) includes the use of afatinib and other EGFR tyrosine kinase inhibito...
The first-line treatment for advanced epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) includes the use of afatinib and other EGFR tyrosine kinase inhibitors (EGFR-TKIs). While generally well tolerated, a small subset of patients will develop drug-induced interstitial lung disease (ILD) which could lead to drug discontinuation or even death. A 58-year-old female with stage IV NSCLC treated with afatinib presented with dyspnea and rapidly progressive hypoxemia. Imaging of the lungs demonstrated ground glass opacities. Infectious workup was unrevealing, and since drug-induced ILD was suspected early on presentation, high dose corticosteroids were initiated leading to clinical improvement. While the incidence of afatinib-induced ILD is rare, the consequences may be serious and potentially fatal. The presentation is often non-specific and may mimic other common respiratory pathologies making the diagnosis challenging. If therapeutic measures such as corticosteroids are initiated promptly, they can be life-saving.
- Hydroxysafflor Yellow A Suppresses Platelet Activating Factor-Induced Activation of Human Small Airway Epithelial Cells. [Journal Article]
- FPFront Pharmacol 2018; 9:859
- Hydroxysafflor yellow A (HSYA) is a chemical component isolated from the Chinese medicine Carthamus tinctorius L. HSYA has numerous pharmacological effects, including protecting against and mitigatin...
Hydroxysafflor yellow A (HSYA) is a chemical component isolated from the Chinese medicine Carthamus tinctorius L. HSYA has numerous pharmacological effects, including protecting against and mitigating some respiratory diseases such as acute lung injury and chronic obstructive pulmonary disease; however, its effect on asthma remains unclear. We previously found that HSYA attenuated ovalbumin-induced allergic asthma in guinea pigs. Platelet activating factor (PAF) is a phospholipid mediator of inflammation and an important factor in the pathological process of asthma. In this study, we investigated the anti-inflammatory effects of HSYA and its underlying mechanisms in PAF-induced human small airway epithelial cells (HSAECs). PAF-activated cells were pretreated with HSYA and/or the PAF receptor inhibitor, ginkgolide B, and we observed changes in the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha, monolayer permeability of HSAECs, and inflammatory signaling pathways. HSYA attenuated the PAF-induced increase in expression of inflammatory factors and destruction of cell-barrier function, and inhibited the expression of protein kinase C, mitogen-activated protein kinases, activator protein-1, and nuclear factor-κB activation induced by PAF. These findings suggest that HSYA may represent a potential new drug for the treatment of asthma.
- Dynamic Changes and Drug-Induced Selection of Resistant Clones in a Patient With EGFR-Mutated Adenocarcinoma That Acquired T790M Mutation and Transformed to Small-Cell Lung Cancer. [Journal Article]
- CLClin Lung Cancer 2018 Jul 26
- Attenuation of antimalarial agent hydroxychloroquine on TNF-α-induced endothelial inflammation. [Journal Article]
- IIInt Immunopharmacol 2018 Aug 15; 63:261-269
- CONCLUSIONS: This work shows the inhibitory effect of HCQ on endothelial inflammatory response through, at least in part, blocking NF-κB, p38 and JNK pathways. Our findings suggest that HCQ may be a promising approach for the treatment of inflammatory vascular disease beyond its immunomodulatory actions.
- Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy. [Journal Article]
- IJInt J Oncol 2018 Aug 14
- Lung cancer is a prevalent disease and is one of the leading causes of mortality worldwide. Despite the development of various anticancer drugs, the prognosis of lung cancer is relatively poor. Metas...
Lung cancer is a prevalent disease and is one of the leading causes of mortality worldwide. Despite the development of various anticancer drugs, the prognosis of lung cancer is relatively poor. Metastasis of lung cancer, as well as chemoresistance, is associated with a high mortality rate for patients with lung cancer. Camptothecin (CPT) is a well-known anticancer drug, which causes cancer cell apoptosis via the induction of DNA damage; however, the cytotoxicity of CPT easily reaches a plateau at a relatively high dose in lung cancer cells, thus limiting its efficacy. The present study demonstrated that CPT may induce autophagy in two human non‑small cell lung cancer cell lines, H1299 and H460. In addition, the results of a viability assay and Annexin V staining revealed that CPT-induced autophagy could protect lung cancer cells from programmed cell death. Conversely, the cytotoxicity of CPT was increased when autophagy was blocked by 3-methyladenine treatment. Furthermore, inhibition of autophagy enhanced the levels of CPT-induced DNA damage in the lung cancer cell lines. Accordingly, these findings suggested that autophagy exerts a protective role in CPT-treated lung cancer cells, and the combination of CPT with a specific inhibitor of autophagy may be considered a promising strategy for the future treatment of lung cancer.
- Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration. [Journal Article]
- SRSci Rep 2018 Aug 13; 8(1):12024
- Asthma is a phenotypically heterogeneous disease. In severe asthma, airway inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a limited number of drug candidates are in deve...
Asthma is a phenotypically heterogeneous disease. In severe asthma, airway inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a limited number of drug candidates are in development to address this unmet clinical need. Live biotherapeutics derived from the gut microbiota are a promising new therapeutic area. MRx0004 is a commensal Bifidobacterium breve strain isolated from the microbiota of a healthy human. The strain was tested prophylactically and therapeutically by oral gavage in a house dust mite mouse model of severe asthma. A strong reduction of neutrophil and eosinophil infiltration was observed in lung bronchoalveolar lavage fluid following MRx0004 treatment. Peribronchiolar and perivascular immunopathology was also reduced. MRx0004 increased lung CD4+CD44+ cells and CD4+FoxP3+ cells and decreased activated CD11b+ dendritic cells. Cytokine analysis of lung tissue revealed reductions of pro-inflammatory cytokines and chemokines involved in neutrophil migration. In comparison, anti-IL-17 antibody treatment effectively reduced neutrophilic infiltration and increased CD4+FoxP3+ cells, but it induced lung eosinophilia and did not decrease histopathology scores. We have demonstrated that MRx0004, a microbiota-derived bacterial strain, can reduce both neutrophilic and eosinophilic infiltration in a mouse model of severe asthma. This novel therapeutic is a promising next-generation drug for management of severe asthma.
- HIV Tat-TIP30 interaction promotes metastasis by enhancing the nuclear translocation of Snail in lung cancer cell lines. [Journal Article]
- CSCancer Sci 2018 Aug 12
- Lung cancer patients with human immunodeficiency virus (HIV) have a poorer prognosis than do patients without HIV infection. HIV1 Tat is a secreted viral protein that penetrates the plasma membrane a...
Lung cancer patients with human immunodeficiency virus (HIV) have a poorer prognosis than do patients without HIV infection. HIV1 Tat is a secreted viral protein that penetrates the plasma membrane and interacts with a number of proteins in non-HIV-infected cells. The loss of function of Tat-interacting protein 30 (TIP30) has been linked to metastasis in non-small cell lung cancer (NSCLC). However, it is unknown how the interaction of HIV1 Tat with TIP30 regulates the metastasis of NSCLC cells. In this study, the overexpression of TIP30 decreased the TGF-β-induced epithelial-to-mesenchymal transition (EMT) and invasion of NSCLC cells, whereas the knockdown of TIP30 promoted EMT, invasion and stemness. Exposure to recombinant HIV1 Tat proteins promoted EMT and invasion. A mechanistic study showed that the interaction of HIV1 Tat with TIP30 blocked the binding of TIP30 to importin-β, which is required for the nuclear translocation of Snail. Indeed, the loss of TIP30 promoted the nuclear translocation of Snail. In vivo studies demonstrated that the overexpression of TIP30 inhibited the metastasis of NSCLC cells. In contrast, the coexpression of HIV1 Tat and TIP30 diminished the inhibitory effect of TIP30 on metastasis. Immunohistochemistry confirmed that TIP30 overexpression reduced the nuclear localization of Snail, whereas the coexpression of HIV1 Tat and TIP30 increased nuclear Snail in metastatic tumors. In conclusion, the binding of HIV1 Tat to TIP30 enhanced EMT and metastasis by regulating the nuclear translocation of Snail. Targeting Tat-interacting proteins may be a potential therapeutic strategy to prevent metastasis in NSCLC patients with HIV infection. This article is protected by copyright. All rights reserved.
- In silico and in vitro analysis of coumarin derivative induced anticancer effects by undergoing intrinsic pathway mediated apoptosis in human stomach cancer. [Journal Article]
- PPhytomedicine 2018 Jul 15; 46:119-130
- CONCLUSIONS: Our study denotes that SSBC could be very effective against AGS by inducing apoptosis through intrinsic pathway and recommended for in vivo and human trials.
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- Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin-induced diabetic male rats. [Journal Article]
- EPExp Physiol 2018 Aug 08
- What is the central question of this study? Whether a low dose of inorganic nitrate supplementation can prevent the testicular functional and structural alterations in streptozotocin-induced type 1 d...
What is the central question of this study? Whether a low dose of inorganic nitrate supplementation can prevent the testicular functional and structural alterations in streptozotocin-induced type 1 diabetic male rats? What is the main finding and it's important? Treatment with a low dose of inorganic nitrate for 2 months had protective effects on male reproductive system. Improved body weight loss, sperm and testis parameters, spermatogenesis index, and testis histology as well as increased serum testosterone levels in diabetic rats. These favorable effects may be associated with increased serum insulin and decreased serum glucose, and with modulating of apoptosis in testis.