Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and Pro-Inflammatory Cytokines.

Extracellular lipopolysaccharide (LPS) released from bacteria cells can enter the bloodstream and cause septic complications with excessive host inflammatory responses. Target-specific strategies to inactivate inflammation mediators have largely failed to improve the prognosis of septic patients in clinical trials. By utilizing their high density of positive charges, de novo designed peptide nanonets are shown to selectively entrap the negatively charged LPS and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Calcaratarin D, a labdane diterpenoid, attenuates mouse asthma via modulating alveolar macrophage function.

Background And Purpose: Alveolar macrophages (AMs) contribute to airway inflammation and remodelling in allergic asthma. Calcaratarin D (CalD), a labdane diterpenoid from rhizomes of the medicinal plant Alpinia calcarata, has recently been shown to possess anti-inflammatory properties. The present study evaluated protective effects of CalD in a house dust mite (HDM)-induced asthma mouse model.

Ultrastructural Characteristics of DHA-Induced Pyroptosis.

Microglial cells are resident macrophages of the central nervous system (CNS) that respond to bioactive lipids such as docosahexaenoic acid (DHA). Low micromolar concentrations of DHA typically promote anti-inflammatory functions of microglia, but higher concentrations result in a form of pro-inflammatory programmed cell death known as pyroptosis. This study used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to investigate the morphological characteristics of pyroptosis in BV-2 microglial cells following exposure to 200 µM DHA.

Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD.

Corticosteroid is the most widely used anti-inflammatory agent for asthma and chronic obstructive pulmonary disease (COPD). However, most of the severe asthmatics and COPD patients show poor response to the anti-inflammatory benefits of corticosteroids. Corticosteroid resistance is a major therapeutic challenge to the treatment of severe asthma and COPD.

Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects.

Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases.

Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology.

Isthmin is a novel vascular permeability inducer that functions through cell-surface GRP78-mediated Src activation.

Aims: Isthmin (ISM) is a recently identified 60 kDa secreted angiogenesis inhibitor. Two cell-surface receptors for ISM have been defined, the high-affinity glucose-regulated protein 78 kDa (GRP78) and the low-affinity αvβ5 integrin. As αvβ5 integrin plays an important role in pulmonary vascular permeability (VP) and ISM is highly expressed in mouse lung, we sought to clarify the role of ISM in VP.

Specificity and inhibitory mechanism of andrographolide and its analogues as antiasthma agents on NF-κB p50.

Andrographolide (1) is a diterpenoid lactone with an α,β-unsaturated lactone group that inhibits NF-κB DNA binding. Andrographolide reacts with the nucleophilic Cys62 of NF-κB p50 through a Michael addition at the Δ(12(13)) exocylic double bond to form a covalent adduct. Using computer docking, site-directed mutagenesis, and mass spectrometry, the noncovalent interactions between andrographolide and additional binding site residues other than Cys62 were found to be essential for the covalent incorporation of andrographolide.

SRS06, a new semisynthetic andrographolide derivative with improved anticancer potency and selectivity, inhibits nuclear factor-κB nuclear binding in the A549 non-small cell lung cancer cell line.

Background: Andrographolide has been reported with anticancer and anti-inflammatory properties through the inhibition of the activity of signaling molecules such as v-Src, nuclear factor-κB (NF-κB), STAT3, and PI3K. NF-κB has been proven to promote cancer cell survival, and targeting this pathway will halt the growth of cancer cells. Efforts have been made to produce semisynthetic derivatives of andrographolide with improved anticancer potency and selectivity.

Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin.

Artesunate (ART) is an anti-malaria drug that has been shown to exhibit anti-tumor activity, and functional lysosomes are reported to be required for ART-induced cancer cell death, whereas the underlying molecular mechanisms remain largely elusive. In this study, we aimed to elucidate the molecular mechanisms underlying ART-induced cell death. We first confirmed that ART induces apoptotic cell death in cancer cells.

Laminin drives survival signals to promote a contractile smooth muscle phenotype and airway hyperreactivity.

Increased airway smooth muscle (ASM) mass is believed to underlie the relatively fixed airway hyperresponsiveness (AHR) in asthma. Developments of therapeutic approaches to reverse airway remodeling are impeded by our lack of insight on the mechanisms behind the increase in mass of contractile ASM cells. Increased expression of laminin, an extracellular matrix protein, is associated with asthma.

Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft model and potential mechanism through MAPK signaling.

We investigated the antiproliferative effect of genistein, and its antileukemia effect in combination with cytosine arabinoside (ara-C) in acute myeloid leukemia (AML). Optimal dosage of genistein as single agent and in combination with ara-C was first determined in vitro. Genistein demonstrated a dose- and time-dependent inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest at G(2)/M phase.