Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

A functional drug delivery platform for targeting and imaging cancer cells based on Pluronic F127.

Functional polymeric micelles play an important role in the efficient delivery of therapeutic drugs into tumours. In this study, a functional drug delivery platform with ligands for targeting and fluorescent imaging was designed based on Pluronic F127 (PF127). Using folic acid (FA) and fluorescein isothiocyanate (FITC) to chemically conjugate with PF127, two functional polymers, Pluronic F127-FA (PF127-FA) and Pluronic F127-FITC (PF127-FITC), were synthesized. Solasodine-loaded micelles were then prepared via the thin-film hydration method. By employing A549 and HeLa cells, the results of in vitro cell assays performed using confocal laser scanning microscopy and flow cytometry suggested that the proposed micelles could provide the desired specific targeting and fluorescent imaging functions. In addition, the results of in vitro cytotoxicity experiments showed that the growth inhibition rates of A549 and HeLa cells treated with solasodine-loaded micelles were remarkably higher than those of cells treated with free solasodine. Solasodine-loaded micelles exhibited a more distinct inhibitory effect against HeLa cells than against A549 cells. Thus, an effective drug delivery system for targeting and imaging cancer cells was developed.

The aryl hydrocarbon receptor suppresses osteoblast proliferation and differentiation through the activation of the ERK signaling pathway.

Ahr activation is known to be associated with synovitis and exacerbated rheumatoid arthritis (RA), but its contributions to bone loss have not been completely elucidated. Osteoblast proliferation and differentiation are abnormal at the erosion site in RA. Here, we reported that the expression of Ahr was increased in the hind paws' bone upon collagen-induced arthritis (CIA) in mice, and the levels of Ahr were negatively correlated with bone mineral density (BMD). In addition, immunofluorescent staining showed that the high expression of Ahr was mainly localized in osteoblasts from the CIA mice compared to normal controls. Moreover, the luciferase intensity of Ahr in the nucleus increased by 12.5% in CIA osteoblasts compared to that in normal controls. In addition, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activation of the Ahr inhibited pre-osteoblast MC3T3-E1 cellular proliferation and differentiation in a dose-dependent manner. Interestingly, the levels of alkaline phosphatase (ALP) mRNA expression in the osteoblasts of CIA mice were reduced compared to normal controls. In contrast, decreased ALP expression by activated Ahr was completely reversed after pretreatment with an Ahr inhibitor (CH-223191) in MC3T3-E1 cell lines and primary osteoblasts on day 5. Our data further showed that activation of Ahr promoted the phosphorylation of ERK after 5days. Moreover, Ahr-dependent activation of the ERK signaling pathway decreased the levels of proliferation cells and inhibited ALP activity in MC3T3-E1 cells. These results demonstrated that the high expression of Ahr may suppress osteoblast proliferation and differentiation through activation of the ERK signaling pathway, further enabling bone erosion in CIA mice.

Novel lycorine derivatives as anticancer agents: synthesis and in vitro biological evaluation.

Lycorine, which is the most abundant alkaloid isolated from the Amaryllidaceae family of plants, reportedly exhibits promising anticancer activities. Herein, a series of novel lycorine derivatives were synthesized and evaluated for their in vitro inhibitory activities against seven different cancer cell lines, including A549, HCT116, SK-OV-3, NCI-H460, K562, MCF-7 and HL-60. The results indicated that compounds bearing diverse amine substituents at the C-2 position demonstrated good anticancer activities. The selectivity towards different cancer cell lines of the synthesized derivatives is discussed.

Human secreted stabilin-1-interacting chitinase-like protein aggravates the inflammation associated with rheumatoid arthritis and is a potential macrophage inflammatory regulator in rodents.

OBJECTIVE: To study the relationship between the human secreted protein stabilin-1-interacting chitinase-like protein (SI-CLP) and rheumatoid arthritis (RA). METHODS: The expression of SI-CLP in peripheral blood mononuclear cells (PBMCs) and synovial fluid from patients with RA and the effects of cytokines on SI-CLP expression were examined by Western blotting. Fluorescence-activated cell sorting analysis was performed to investigate the binding between SI-CLP and cells. Bone marrow-derived macrophages were isolated from wild-type and SI-CLP(-/-) mice, and real-time quantitative polymerase chain reaction was performed to detect the levels of messenger RNA for cytokines or SI-CLP in SI-CLP- or cytokine-treated macrophages. Histologic studies were conducted to evaluate inflammation and the expression of interleukin-12 (IL-12), IL-13, and SI-CLP in lesions. Enzyme-linked immunosorbent assays were used to detect the cytokine levels in bone marrow-derived macrophages. Rats or mice with collagen-induced arthritis (CIA) and SI-CLP(-/-) mice were used to study the function of SI-CLP in RA. RESULTS: SI-CLP expression was increased in PBMCs and detectable in synovial fluid from patients with RA. Administration of SI-CLP to rats with CIA aggravated arthritis-associated inflammation. SI-CLP was specifically attached to the surface protein of macrophages, which elevated the expression of IL-1ß, IL-6, IL-12, and IL-13 in macrophages and mouse bone marrow-derived macrophages, up-regulating ERK phosphorylation. Moreover, SI-CLP was up-regulated by both IL-12 and IL-13 through JNK and JAK/STAT signaling, respectively. Knockout of SI-CLP resulted in a decrease in the expression of IL-1ß, IL-6, IL-12, and IL-13 and lower susceptibility to CIA compared with wild-type mice. SI-CLP treatment also aggravated arthritis-related inflammation in wild-type and SI-CLP(-/-) mice. CONCLUSION: SI-CLP functions as a regulator of the inflammatory response by macrophages. The decrease in inflammation-associated cytokine levels resulting from SI-CLP knockout may explain the lower susceptibility to CIA in SI-CLP(-/-) mice.

Antitumor and immunomodulatory activities of a polysaccharide from Artemisia argyi.

A water-soluble polysaccharide (FAAP-02), composed of N-acetyl-D-glucosamine, glucose, mannose, galactose, rhamnose, arabinose, xylose and ribose, with an average molecular weight of 5169 Da, was isolated from Artemisia argyi. The antitumor and immunomodulatory activities of FAAP-02 were evaluated in Sarcoma 180 (S180) tumor-bearing mice by intraperitoneal administration. As a result, FAAP-02 significantly inhibited the growth of the S180 transplanted tumors and prolonged the survival time of the tumor-bearing mice. Moreover, FAAP-02 could obviously increase the thymus and spleen indices, the levels of serum Interleukin 2 (IL-2), Interleukin 6 (IL-6), Interleukin 12 (IL-12) and tumor necrosis factor-α (TNF-α), and the expression of CD4+ and CD8+ splenic T lymphocytes which were suppressed by the transplanted tumor or/and 5-fluorouracil (5-FU) in the mice. These results indicated that the antitumor activity of FAAP-02 might be associated with its immunostimulatory effects.

In vitro antioxidant and cytotoxic properties of ethanol extract of Alpinia oxyphylla fruits.

CONTEXT: Alpinia oxyphylla Miquel (Zingiberaceae) is a traditional Chinese herbal medicine widely used for the treatment of intestinal disorders, urosis and diuresis. However, information about antioxidant and cytotoxic properties of its fruits remains to be elucidated. OBJECTIVE: The ethanol crude extract (CE) and its fractions [petroleum ether fraction (PF), ethyl acetate fraction (EF), n-butanol fraction (BF) and water fraction (WF) extracted by petroleum ether, ethyl acetate, n-butanol and water, respectively] of A. oxyphylla fruits were investigated for their antioxidant activity and cytotoxicity. MATERIALS AND METHODS: The total phenolic content (TPC) and antioxidant activity of the extracts were determined by Folin-Ciocalteu reagent, 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)), Trolox equivalent antioxidant capacity and reducing power assay. Cytotoxicity of the extracts (0-200 µg/mL) was tested on six human cancer cell lines (breast cancer cell line, cervix carcinoma cell line, lung adenocarcinoma cell line, liver carcinoma cell line, gastric cancer cell line and colon cancer cell line) using the sulforhodamine B assay. RESULTS: The TPC of extracts varied from 8.2 to 20.3 mg gallic acid equivalents/g dry weight. DPPH radical scavenging effect of extracts decreased in the order of EF > BF > CE > PF > WF, with IC50 values ranging from 74.7 to 680.8 µg/mL. 2,2-azo-bis(3-Ethylbenzothiazoline-6-sulfoic acid) diammonium salt scavenging activity ranged from 0.118 to 0.236 mmol Trolox equivalence/mg extract. The extracts exhibited concentration-dependent reducing power, and EF showed the highest reducing ability. A satisfactory correlation (R(2) > 0.826) between TPC and antioxidant activity was observed. In addition, EF, PF and CE exhibited potent anticancer effects on six cancer cell lines with IC50 values ranging from 40.1 to 166.3 µg/mL. DISCUSSION AND CONCLUSION: The ethanol extract of A. oxyphylla fruit, especially the EF, was found to possess potent antioxidant and anticancer activities, and thus a great potential for the application in food and drug products.

3,5-Dicaffeoylquinic acid isolated from Artemisia argyi and its ester derivatives exert anti-leucyl-tRNA synthetase of Giardia lamblia (GlLeuRS) and potential anti-giardial effects.

An aqueous ethanol extract of Artemisia argyi inhibited the aminoacylation activity of LeuRS from Giardia lamblia (GlLeuRS). The bioassay-guided fractionation of the extract led to the isolation of 3,5-dicaffeoylquinic acid (1), with an IC50 of 5.82 µg/mL. The ester derivatives of 1 were also found to possess strong anti-GlLeuRS effects, with IC50 values of 1.79, 5.51 and 2.56 µg/mL respectively. Anti-giardial assay showed that the derivatives, especially 3,5-dicaffeoylquinic acid propyl ester (4) (IC50=4.62 µg/mL), were effective at killing G. lamblia.