Impaired post-stroke collateral circulation in sickle cell anemia mice.

Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra.

Acrylamide, an air pollutant, enhances allergen-induced eosinophilic lung inflammation via group 2 innate lymphoid cells.

Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s.

AhR Mediated Activation of Pro-Inflammatory Response of RAW 264.7 Cells Modulate the Epithelial-Mesenchymal Transition.

Pulmonary fibrosis, a chronic lung disease caused by progressive deterioration of lung tissue, is generated by several factors including genetic and environmental ones. In response to long-term exposure to environmental stimuli, aberrant tissue repair and epithelial cell-to- mesenchymal cell transition (EMT) trigger the subsequent progression of pulmonary fibrotic diseases. The Aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by ligands providing lung dysfunction when activated by environmental toxins, such as polycyclic aromatic hydrocarbons.

Outcome of improved care bundle in acute respiratory failure patients.

Background: Prolonged physical immobilization has negative effects on patients on mechanical ventilation (MV).

Aims: To introduce a quality improvement programme with early mobilization on the outcomes of patients on MV in the intensive care unit (ICU). We particularly studied the impact of the ABCDE (daily Awakening, Breathing trial, drug Co-ordination, Delirium survey and treatment, and Early mobilization) bundle on the outcome of MV patients with acute respiratory failure in the ICU.

Stimulatory effect of gastroesophageal reflux disease (GERD) on pulmonary fibroblast differentiation.

Epidemiological studies indicate that prolonged micro-aspiration of gastric fluid is associated in gastroesophageal reflux disease with the development of chronic respiratory diseases, possibly caused by inflammation-related immunomodulation. Therefore, we sought to ascertain the effect of gastric fluid exposure on pulmonary residential cells. The expression of α-smooth muscle actin as a fibrotic marker was increased in both normal human pulmonary fibroblast cells and mouse macrophages.

Pomegranate extract inhibits migration and invasion of oral cancer cells by downregulating matrix metalloproteinase-2/9 and epithelial-mesenchymal transition.

Discovering drug candidates for the modulation of metastasis is of great importance in inhibiting oral cancer malignancy. Although most pomegranate extract applications aim at the antiproliferation of cancer cells, its antimetastatic effects remain unclear, especially for oral cancer cells. The aim of this study is to evaluate the change of two main metastasis characters, migration and invasion of oral cancer cells.

Unfolded Protein Response (UPR) in Survival, Dormancy, Immunosuppression, Metastasis, and Treatments of Cancer Cells.

The endoplasmic reticulum (ER) has diverse functions, and especially misfolded protein modification is in the focus of this review paper. With a highly regulatory mechanism, called unfolded protein response (UPR), it protects cells from the accumulation of misfolded proteins. Nevertheless, not only does UPR modify improper proteins, but it also degrades proteins that are unable to recover.

Discovery of Pyrazolo[4,3-]quinolines Derivatives as Potential Anti-Inflammatory Agents through Inhibiting of NO Production.

The synthesis and anti-inflammatory effects of certain pyrazolo[4,3-]quinoline derivatives ⁻ are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells.

Aryl hydrocarbon receptor-ligand axis mediates pulmonary fibroblast migration and differentiation through increased arachidonic acid metabolism.

Pulmonary fibroblast migration and differentiation are critical events in fibrogenesis; meanwhile, fibrosis characterizes the pathology of many respiratory diseases. The role of aryl hydrocarbon receptor (AhR), a unique cellular chemical sensor, has been suggested in tissue fibrosis, but the mechanisms through which the AhR-ligand axis influences the fibrotic process remain undefined. In this study, the potential impact of the AhR-ligand axis on pulmonary fibroblast migration and differentiation was analyzed using human primary lung fibroblasts HFL-1 and CCL-202 cells.

Discovery of 3-phenylquinolinylchalcone derivatives as potent and selective anticancer agents against breast cancers.

A number of 3-phenylquinolinylchalcone derivatives were synthesized and evaluated in vitro for their antiproliferative activities against three breast cancer cell lines (MCF-7, MDA-MB-231, and SKBR-3), and a non-cancer normal epithelial cell line (H184B5F5/M10). Among them, (E)-3-[3-(4-methoxyphenyl)quinolin-2-yl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (7) was active against the growth of MCF-7, MDA-MB-231, and SKBR-3 with IC50 values of 1.05, 0.

Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model.

Background: Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model.

Methods: Forty male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, sildenafil + sham, and sildenafil + I/R groups.

Synthesis and anti-inflammatory evaluations of β-lapachone derivatives.

β-Lapachone (β-LAPA), a natural product from the lapacho tree in South America, is a potential chemotherapeutic agent that exhibit a wide variety of pharmacological effects such as anti-virus, anti-parasitic, anti-cancer, and anti-inflammatory activities. In order to discover novel anti-inflammatory agents, we have synthesized a series of β-LAPA derivatives for evaluation. Among them, 4-(4-methoxyphenoxy)naphthalene-1,2-dione (6b) was found to be able to inhibit NO and TNF-α released in LPS-induced Raw 264.

Synthesis of 6-substituted 9-methoxy-11H-indeno[1,2-c]quinoline-11-one derivatives as potential anticancer agents.

We have synthesized certain 6-substituted 9-methoxy-11H-indeno[1,2-c]quinolin-11-ones for antiproliferative evaluation. Results indicated that 6-alkylamine derivatives, 6-[2-(dimethylamino)ethylamino]-9-methoxy-11H-indeno[1,2-c]quinolin-11-one (5a) and its 6-[3-(dimethylamino)propylamino] derivative, 5b, were able to inhibit cells growth completely at a concentration of 100 μM while most of the 6-arylamine derivatives 6b-6h were inactive at the same concentration. Comparable mean GI(50) (drug molar concentration causing 50% cell growth inhibition) values for 5a (3.

Identification of furo[3', 2':3,4]naphtho[1,2-d]imidazole derivatives as orally active and selective inhibitors of microsomal prostaglandin E(2) synthase-1 (mPGES-1).

This study describes the synthesis and anti-inflammatory effects of furo[3', 2':3,4]naphtho[1,2-d] imidazole derivatives. Among these furo[3', 2':3,4]naphtho[1,2-d]imidazole derivatives, 2-(4-methoxyphenyl)furo [3', 2':3,4]naphtho[1,2-d]imidazole (12) exhibited a strong inhibitory activity against LPS-induced PGE(2) production, with an IC(50) value of 47 nM. Compound 12 is then further examined for its inhibitory effects in the protein expression of COX-2 and microsomal prostaglandin E(2) synthase-1 (mPGES-1) in Raw 264.

Synthesis and antiproliferative evaluation of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives.

A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3-(dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.

Synthesis and antiproliferative evaluation of 2,3-diarylquinoline derivatives.

A number of 2,3-diarylquinoline derivatives were synthesized and evaluated for antiproliferative activities against the growth of six cancer cell lines including human hepatocellular carcinoma (Hep G2 and Hep 3B), non-small cell lung cancer (A549 and H1299), and breast cancer (MCF-7 and MDA-MB-231) cell lines. The preliminary results indicated that 6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline (16b) was one of the most active compounds against the growth of Hep 3B, H1299, and MDA-MB-231 with a GI(50) value of 0.71, 1.

Synthesis and antiproliferative evaluation of certain iminonaphtho[2,3-b]furan derivatives.

Certain iminonaphtho[2,3-b]furan derivatives were synthesized from their respective carbonyl precursors in the regiospecific and the stereospecific manners. These compounds were evaluated for their antiproliferative effects against four human carcinoma cells (MCF7, NCI-H460, SF-268, and K562) and the normal fibroblast cell line (Detroit 551). Among them, (Z)-4-(hydroxyimino)naphtho[2,3-b]furan-9(4H)-one (8) and (Z)-4-methoxy-iminonaphtho[2,3-b]furan-9(4H)-one (9) exhibited GI(50) values of 0.

Pretreatment of vitamin D3 ameliorates lung and muscle injury induced by reperfusion of bilateral femoral vessels in a rat model.

Background: Peripheral arterial occlusive disease (PAOD) is a challenge in peripheral vascular disease. Clinical observations show reperfusion of occluded vessels may cause compartment syndrome or remote organ injury. Less well known is the role of vitamin D3 in tissue injury; therefore, we attempted to determine whether vitamin D3 could alleviate local and remote organ injury induced by reperfusion of occluded vessels in animal models.

Synthesis and antiproliferative evaluation of 6-arylindeno[1,2-c]quinoline derivatives.

A number of 6-arylindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities against the growth of five cancer cell lines including human hepatocelluar carcinoma (Hep G2, Hep 3B and Hep2.2.1), non-small cell lung cancer (A549 and H1299), and normal diploid embryonic lung cell line (MRC-5).

Furo[3',2':3,4]naphtho[1,2-d]imidazole derivatives as potential inhibitors of inflammatory factors in sepsis.

Synthesis and anti-inflammatory effects of certain furo[3',2':3,4]naphtho[1,2-d]imidazole derivatives 12-18 were studied. These compounds were synthesized from naphtho[1,2-b]furan-4,5-dione (10) which in turn was prepared from the known 2-hydroxy-1,4-naphthoquinone (7) in a one pot reaction. Furo[3',2':3,4]naphtho[1,2-d]imidazole (12) was inactive (IC(50) value of >30 microM) while its 5-phenyl derivative 13, with an IC(50) value of 16.

Macrophage activation by gastric fluid suggests MMP involvement in aspiration-induced lung disease.

Asthma occurs in more than 5% of the population in industrialized countries and is now characterized as a chronic inflammatory disease. The chronic aspiration of gastric fluid is considered by many investigators to be a primary inflammatory factor exacerbating or predisposing patients to asthma, with more than 50 medical papers per year linking asthma with gastroesophageal reflux disease (GERD), which can lead to aspiration events. However, the mechanisms involved in the inflammatory effects caused by gastric-fluid aspiration are not clear at the present time.

Apoptin T108 phosphorylation is not required for its tumor-specific nuclear localization but partially affects its apoptotic activity.

Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in human tumor cells but not in normal cells. In addition, Apoptin also exhibits tumor-specific nuclear localization and tumor-specific phosphorylation on threonine 108 (T108). Here, we studied the effects of T108 phosphorylation on the tumor-specific nuclear localization and apoptotic activity of Apoptin.

The F-box protein Fbxo7 interacts with human inhibitor of apoptosis protein cIAP1 and promotes cIAP1 ubiquitination.

Human cIAP1 protein is a member of the inhibitor of apoptosis proteins (IAPs) that are involved in apoptosis regulation and an increasing number of other functions, including cell cycle and intracellular signal transduction. In order to identify novel proteins involved in cIAP1 regulation, we performed a yeast two-hybrid screen and identified an F-box protein Fbxo7 as a cIAP1 interacting protein. Co-immunoprecipitation assay showed that cIAP1 can interact with Fbxo7 in human cells.

The viral death protein Apoptin interacts with Hippi, the protein interactor of Huntingtin-interacting protein 1.

Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in human tumor cells but not in normal cells. The tumor-specific activity of Apoptin is correlated with its nuclear localization in tumor cells. In an attempt to elucidate the molecular mechanism of Apoptin-induced apoptosis, we identified human Hippi, the protein interactor and apoptosis co-mediator of Huntingtin interacting protein 1, as one of the Apoptin-associated proteins by yeast two-hybrid screen.