Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-γ (IFN-γ), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.

Abstract. Lung cancer has one of the highest mortality rates among malignancies globally, and smoking has been documented as the main cause of lung cancer. Nicotinic acetylcholine receptors (nAChRs) were initially identified as notable regulators of the nervous system. In addition to their function in the brain, accumulating evidence indicates that nAChRs perform a host of diverse functions in almost all non-neuronal mammalian cells. The homomeric α7nAChR, a subtype of nAChRs, is responsible for the proliferative, pro-angiogenic and pro-metastatic effects of nicotine in lung cancer. Provided the association of cigarette smoking with several disease types such as cardiovascular disease, the α7nAChR-mediated signaling pathway has been implicated in the pathophysiology of lung cancer. Currently, strategies that target the α7nAChR including α7nAChR antagonists are considered to be potentially useful anticancer drugs for therapeutic purposes. Thus, the present review assesses current understanding of the function and underlying molecular mechanisms of α7nAChR in lung cancer and evaluates how targeting α7nAChR may result in novel therapeutic methods. IntroductionLung cancer is one of the most commonly occurring carcinoma types globally and has limited treatment options for advanced-stage disease (1). Lung cancer is a heterogeneous disease comprised of two main pathological types: Non-small-cell lung cancer (NSCLC) which accounts for 70-80% of all lung cancer cases and small-cell lung cancer (SCLC) which accounts for ~20% of all lung cancer cases (2). NSCLCs may be divided into three subtypes: Squamous-cell carcinoma (25-30% of all lung cancer cases), adenocarcinoma (~40% of all lung cancer cases) and large-cell carcinoma (10-15% of all lung cancer cases) (3). SCLC is the second most prevalent form of lung cancer, with a 5-year survival rate of <7% (4). Cigarette smoking is considered to be the main risk factor for lung cancer, and ~90% of all cases are associated with exposure to smoking and second-hand smoking (5). Other contributory factors include residential radon, occupational hazards including exposure to asbestos, arsenic and polycyclic aromatic hydrocarbons, radiation, coal smoke, indoor emission of fuel burning, outdoor pollution, previous non-malignant lung diseases in addition to a family history of tumors (6,7). Squamous-cell, large-cell and SCLC are the most commonly identified types of lung cancer present in smokers (8,9). In contrast, adenocarcinoma is the lung cancer type most commonly identified in non-smokers (10).Cigarette smoke is a mixture of thousands of chemical compounds, a number of which have potent carcinogenic potential including polycyclic aromatic hydrocarbons, nicotine and the nicotine-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyrydyl)-1-butanone (NNK) and N-nitrosonornicotine (11). The most harmful and addictive component is nicotine (11). These carcinogens and their metabolites may induce the formation of DNA adducts which result in mutations of a number of key cancer suppressor...

No abstract

No abstract