- Treatment with Eucalyptol Mitigates Cigarette Smoke-Induced Lung Injury through Suppressing ICAM-1 Gene Expression. [Journal Article]
- BRBiosci Rep 2018 May 22
- Objectives : This study was conducted to investigate of the clinical significance of Eucalyptol in treating cigarette smoke-induced lung injury with the potential mechanism involved in the event. Met...
Objectives : This study was conducted to investigate of the clinical significance of Eucalyptol in treating cigarette smoke-induced lung injury with the potential mechanism involved in the event. Methods : Rats were exposed to air (control) and cigarette smoke (smoking) after they were treated with Eucalyptol (260mg/kg) orally once a day for 12 weeks. Cell counts of bronchoalveolar lavage fluid (BALF), measurements of mean liner intercept (MLI) and mean alveolar number (MAN) and lung function test were executed in experimental animals. Contents of cytokines and intercellular adhesion molecule (ICAM)-1 in BALF and ICAM-1 protein and mRNA expression in lung tissues were determined by ELISA, immunohistochemistry (IHC) and RT-PCR, respectively. Results : A rat model of COPD displayed declining lung function, increased cell counts and cytokine production in BALF and emphysema-like lesions in cigarette smoke-exposed lungs compared to the controls (all P < 0.01). Treatment with Eucalyptol partly reversed lung function decline with obvious decreases in inflammatory cell infiltrate, TNF-a, IL-6 and ICAM-1 expression levels in the challenged lungs (all P < 0.05 and 0.01). Furthermore, oral administration of the drug not only reduced the emphysema-associated lung lesions but also suppressed ICAM-1 protein and mRNA expression in the lungs compared to the control (all P < 0.05 or 0.01). Conclusion: Intervention of Eucalyptol mitigates the ongoing inflammatory process in airways and ameliorates the cigarette smoke-induced lung injury through suppressing ICAM-1 gene expression in the diseased lungs.
- Mycophenolate mofetil-induced colitis in a patient with systemic sclerosis. [Journal Article]
- BCBMJ Case Rep 2018 May 18; 2018
- We present the case of a 44-year-old woman affected by systemic sclerosis (SSc) who was admitted to our department for abdominal pain, nausea, vomiting and fever. Imaging studies showed the presence ...
We present the case of a 44-year-old woman affected by systemic sclerosis (SSc) who was admitted to our department for abdominal pain, nausea, vomiting and fever. Imaging studies showed the presence of a thickened colon wall involving the descending colon and the sigma, while a subsequent endoscopy revealed multiple serpiginous ulcers covered with fibrin and exudates. Under the hypothesis of drug-induced colitis, mycophenolate mofetil (MMF), which she was taking for SSc-related interstitial lung disease (ILD), was readily suspended, with a rapid recovery without further treatment. A follow-up colonoscopy showed the complete resolution of the ulcers. This is the first case of MMF-induced colitis in a patient being treated for SSc-ILD.
- Nasal delivery of chitosan/alginate nanoparticle encapsulated bee (Apis mellifera) venom promotes antibody production and viral clearance during porcine reproductive and respiratory syndrome virus infection by modulating T cell related responses. [Journal Article]
- VIVet Immunol Immunopathol 2018; 200:40-51
- In this study, we administered specially developed chitosan/alginate nanoparticle encapsulated BV (CH/AL-BV) which has slow-releasing properties and mucosal adhesiveness to pig via nasal route and ev...
In this study, we administered specially developed chitosan/alginate nanoparticle encapsulated BV (CH/AL-BV) which has slow-releasing properties and mucosal adhesiveness to pig via nasal route and evaluate whether it can facilitate systemic immune response and improve clearance of porcine reproductive and respiratory syndrome virus (PRRSV). The CH/AL-BV-administered group with PRRSV vaccination showed significantly enhanced Th1-related responses including a high population of CD4+ T lymphocyte and cytokine mRNA levels including interferon-gamma (IFN-γ) and interleukin (IL)-12 and increased PRRSV-specific IgG levels. In the PRRSV challenge experiment, the CH/AL-BV group showed a significant decrease of viral burden in the sera and tissues (lung and bronchial lymph node) and mild interstitial pneumonia signs on both lung gross examination and microscopic evaluation with high levels of PRRSV-specific IgG and viral neutralizing antibody. CH/AL-BV also effectively induced not only Th1-related immune responses including increase in portion of CD4+ T lymphocyte, cytokines (IFN-γ and IL-12), and transcriptional factors (STAT4 and T-bet), but also stimulated IFN-γ-secreting cell families such as CD4+ T lymphocytes and Th/memory cells. Interestingly, the CH/AL-BV group showed decrease in PRRSV-specific immune-suppressive actions, including the T regulatory cell population and its related cytokines (IL-10 and TGF-β) and transcriptional factors (STAT5 and Foxp3). Therefore, nasal-delivered CH/AL-BV may effectively induce non-specific immune stimulating actions, particularly those related to Th1 responses and viral clearance activities against PRRSV infection. Based on these results, CH/AL-BV could be a promising strategy for overcoming the disadvantages of classical PRRSV vaccination and can be applied as a preventive agent against PRRSV and other viral diseases, particularly those with immune-suppressive characteristics.
- Transient asymptomatic pulmonary opacities during osimertinib treatment and its clinical implication. [Journal Article]
- JTJ Thorac Oncol 2018 May 15
- CONCLUSIONS: TAPOs are frequently observed with osimertinib treatment and may be mistaken for isolated pulmonary progression or drug induced ILD. Given the lack of serious clinical deterioration, it is reasonable to continue osimertinib with regular CT scan follow-up. For further clinical validation of TAPOs, long-term follow-up and large studies are warranted.
- Case of drug-induced interstitial lung disease secondary to adalimumab. [Journal Article]
- BCBMJ Case Rep 2018 May 15; 2018
- We report a rare case of drug-induced intestinal lung disease (ILD) secondary to adalimumab, a tumour necrosis factor alpha-receptor blocker. A 52-year-old smoker with ankylosing spondylitis, treated...
We report a rare case of drug-induced intestinal lung disease (ILD) secondary to adalimumab, a tumour necrosis factor alpha-receptor blocker. A 52-year-old smoker with ankylosing spondylitis, treated with adalimumab, presented with progressive breathlessness. A high resolution CT chest demonstrated predominantly upper-zone patchy ground glass changes and small bilateral pleural effusions. Bronchoscopy and bronchoalveolar lavage showed no evidence of infection or malignant cells and an echocardiogram was normal. The working diagnosis was that of possible adalimumab-induced ILD. Adalimumab was subsequently stopped. The patient's breathlessness and cough improved on cessation of the drug. A further CT chest several months later showed resolution of the ground glass changes. Adalimumab-induced ILD is rare. We review the literature surrounding this and discuss the diagnostic challenges. This case highlights the importance of considering the possibility of drug-induced lung disease in patients taking adalimumab.
- Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus. [Journal Article]
- NCNat Chem 2018 May 14
- Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here w...
Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.
- Protective effect of standardized extract of Myrtus communis L. (myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study. [Journal Article]
- DCDrug Chem Toxicol 2018 May 11; :1-7
- CONCLUSIONS: Myrtle extract effectively inhibited the inflammation and fibrosis of lung parenchyma in both preventive and therapeutic methods. This effect might be due to the reduction of tissue inflammation and inhibition of oxidative stress. More studies are being carried out to find main mechanisms and separation of active compounds.
- Tabersonine attenuates lipopolysaccharide-induced acute lung injury via suppressing TRAF6 ubiquitination. [Journal Article]
- BPBiochem Pharmacol 2018 May 07; 154:183-192
- Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly ...
Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly isolated from Catharanthus roseus, and a potential drug candidate for treatment of cancer and Alzheimer's disease (AD), however, its anti-inflammatory effect has not been revealed. In this study, we reported that tabersonine ameliorated lipopolysaccharides (LPS)-induced ALI in vivo and inhibited LPS-mediated macrophage activation in vitro. By using murine ALI model, we found that tabersonine significantly attenuated LPS-induced pathological injury in the lung. Tabersonine also inhibited LPS-mediated neutrophil infiltration, elevation of MPO activity and the production of TNF-α, IL-6 and IL-1β. Furthermore, tabersonine inhibited LPS-induced the production of pro-inflammatory mediators such as iNOS, NO and cytokines by suppressing NF-κB and p38 MAPK/MK2 signaling cascades. Tabersonine reduced the K63-linked polyubiquitination of TRAF6. Taken together, these results suggested that tabersonine has anti-inflammatory activities in vitro and in vivo, and is a potential therapeutic candidate for the treatment of ALI/ARDS.
- A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era. [Journal Article]
- BloodBlood 2018 May 09
- The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response...
The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE® format, is FDA approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy. We developed a novel CD19/CD3 bsAb in the single-chain Fv-Fc format (CD19/CD3-scFv-Fc) with a half-life of approximately 5 days. In in vitro experiments, both CD19/CD3-scFv-Fc and blinatumomab induced >90% killing of CLL cells from treatment-naïve patients. Anti-leukemic activity was associated with increased autologous CD8 and CD4 T cell proliferation, activation, and granzyme B expression. In the NOD/SCID/IL2Rγnull patient-derived xenograft mouse model, once-weekly treatment with CD19/CD3-scFv-Fc eliminated >98% of treatment-naïve CLL cells in blood and spleen. By contrast, blinatumomab failed to induce a response, even when administered daily. We next explored the activity of CD19/CD3-scFv-Fc in the context of ibrutinib treatment and ibrutinib resistance. CD19/CD3-scFv-Fc induced more rapid killing of CLL cells from ibrutinib-treated patients than those from treatment-naïve patients. CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring BTK and/or PLCG2 mutations in vitro and in vivo using patient-derived xenograft models. Taken together, these data support investigation of CD19/CD3 bsAbs and other T cell-recruiting bsAbs as immunotherapies for CLL, especially in combination with ibrutinib or as rescue therapy in ibrutinib-resistant disease.
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- Nebulized heparin and N-acetylcysteine for smoke inhalational injury: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(19):e0638
- CONCLUSIONS: On the basis of our experience with this case and limited literature, we posit that nebulized heparin and NAC may be of benefit in patients with inhalational smoke-induced lung injury and mild-to-severe lung injury scores.