Targeting HMGB1 for the treatment of sepsis and sepsis-induced organ injury.

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is present in almost all cells and regulates the activity of innate immune responses in both intracellular and extracellular settings. Current evidence suggests that HMGB1 plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response, immune reactions, cell migration, aging, and cell death. Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs in hosts in response to microbial infections with a proven or suspected infectious etiology and is the leading cause of death in intensive care units worldwide, particularly in the aging population. Dysregulated systemic inflammation is a classic characteristic of sepsis, and suppression of HMGB1 may ameliorate inflammation and improve patient outcomes. Here, we focus on the latest breakthroughs regarding the roles of HMGB1 in sepsis and sepsis-related organ injury, the ways by which HMGB1 are released, and the signaling pathways and therapeutics associated with HMGB1. This review highlights recent advances related to HMGB1: the regulation of HMBG1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury.

Mechanisms explaining the efficacy of psoralidin in cancer and osteoporosis, a review.

Psoralidin (PSO) is a natural phenolic coumarin that is extracted from the seeds of Psoralea corylifolia L. PSO possesses a variety of pharmacological activities, including anti-oxidative, antibacterial, anti-inflammatory, anti-depressive and estrogenic-like effects. Other studies have indicated that PSO plays a beneficial role in multiple disease, especially cancer and osteoporosis. In this review, we first outline the basic background of PSO. Then we introduced the molecular mechanisms and signaling pathways of PSO in multiple cancers to elucidate its anticancer potential via inducing oxidative stress and apoptosis, inhibiting proliferation, promoting autophagy-dependent cell death, and activating the estrogen receptors (ER)-signaling pathway. Finally, we recommend the direction of future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information to help design PSO in other research and future efforts.

LncRNA: Shedding light on mechanisms and opportunities in fibrosis and aging.

Fibrosis is universally observed in multiple aging-related diseases and progressions and is characterized by excess accumulation of the extracellular matrix. Fibrosis occurs in various human organs and eventually results in organ failure. Noncoding RNAs (ncRNAs) have emerged as essential regulators of cellular signaling and relevant human diseases. In particular, the enigmatic class of long noncoding RNAs (lncRNAs) is a kind of noncoding RNA that is longer than 200 nucleotides and does not possess protein coding ability. LncRNAs have been identified to exert both promotive and inhibitory effects on the multifaceted processes of fibrosis. A growing body of studies has revealed that lncRNAs are involved in fibrosis in various organs, including the liver, heart, lung, and kidney. As lncRNAs have been increasingly identified, they have become promising targets for anti-fibrosis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in fibrosis and sheds light on the use of lncRNAs as a potential treatment for fibrosis.

Multifunctional Nanosystem Based on Graphene Oxide for Synergistic Multistage Tumor-Targeting and Combined Chemo-Photothermal Therapy.

Locating nanomedicines at the active sites plays a pivotal role in the nanoparticle-based cancer therapy field. Herein, a multifunctional nanotherapeutic is designed by using graphene oxide (GO) nanosheets with rich carboxyl groups as the supporter for hyaluronic acid (HA)-methotrexate (MTX) prodrug modification via an adipicdihydrazide cross-linker, achieving synergistic multistage tumor-targeting and combined chemo-photothermal therapy. As a tumor-targeting biomaterial, HA can increase affinity of the nanocarrier toward CD44 receptor for enhanced cellular uptake. MTX, a chemotherapeutic agent, can also serve as a tumor-targeting enhancer toward folate receptor based on its similar structure with folic acid. The prepared nanosystems possess a sheet shape with a dynamic size of approximately 200 nm and pH-responsive drug release. Unexpectedly, the physiological stability of HA-MTX prodrug-decorated GO nanosystems in PBS, serum, and even plasma is more excellent than that of HA-decorated GO nanosystems, while both of them exhibit an enhanced photothermal effect than GO nanosheets. More importantly, because of good blood compatibility as well as reduced undesired interactions with blood components, HA-MTX prodrug-decorated GO nanosystems exhibited remarkably superior accumulation at the tumor sites by passive and active targeting mechanisms, achieving highly effective synergistic chemo-photothermal therapeutic effect upon near-infrared laser irradiation, efficient ablation of tumors, and negligible systemic toxicity. Hence, the HA-MTX prodrug-decorated hybrid nanosystems have a promising potential for synergistic multistage tumor-targeting therapy.

Cube-shaped theranostic paclitaxel prodrug nanocrystals with surface functionalization of SPC and MPEG-DSPE for imaging and chemotherapy.

As one of nanomedicine delivery systems (NDSs), drug nanocrystals exhibited an excellent anticancer effect. Recently, differences of internalization mechanisms and subcellular localization of both drug nanocrystals and small molecular free drug have drawn much attention. In this paper, paclitaxel (PTX) as a model anticancer drug was directly labeled with 4-chloro-7-nitro-1, 2, 3-benzoxadiazole (NBD-Cl) (a drug-fluorophore conjugate Ma et al. (2016) and Wang et al. (2016) [1,2] (PTX-NBD)). PTX-NBD was synthesized by nucleophilic substitution reaction of PTX with NBD-Cl in high yield and characterized by fluorescence, XRD, ESI-MS, and FT-IR analysis. Subsequently, the cube-shaped PTX-NBD nanocrystals were prepared with an antisolvent method followed by surface functionalization of SPC and MPEG-DSPE. The obtained specific shaped PTX-NBD@PC-PEG NCs had a hydrodynamic particle size of ∼50nm, excellent colloidal stability, and a high drug-loading content of ∼64%. Moreover, in comparison with free PTX-NBD and the sphere-shaped PTX-NBD nanocrystals with surface functionalization of SPC and MPEG-DSPE (PTX-NBD@PC-PEG NSs), PTX-NBD@PC-PEG NCs remarkably reduced burst release and improved cellular uptake efficiency and in vitro cancer cell killing ability. In a word, the work highlights the potential of theranostic prodrug nanocrystals based on the drug-fluorophore conjugates for cell imaging and chemotherapy.

Pretreatment methods for aquatic plant biomass as carbon sources for potential use in treating eutrophic water in subsurface-flow constructed wetlands.

Plant biomass is usually added to constructed wetlands (CW) to enhance denitrification. In this study, we investigated effects of different pretreatments on two common external plant carbon sources, cattail and reed litter. We determined the average ratio of chemical oxygen demand (COD) to total nitrogen (TN), designated as C/N, in water samples after addition of litter subjected to various pretreatments. The C/N in the water samples ranged from 4.8 to 6.4 after addition of NaOH-pretreated cattail litter, which was four to six times greater than that of water from the Yapu River and 3.84-39.15% higher than that of systems that received untreated cattail litter. The C/N of systems that received H(2)SO(4)-pretreated carbon sources varied from 1.7 to 3.6. These two methods resulted in TN and total phosphorus (TP) levels lower than those in river water. The C/N was 1.4-1.7 after addition of CH(3)COOH-pretreated reed litter, which was 34.87-53.83% higher than that of river water. The C/N was 2.5 in systems that received mild alkali/oxidation-pretreated reeds, which was 30.59% higher than that of systems that received non-pretreated reeds. The residue rates of cattail and reed litter subjected to various pretreatments were greater than 60%. Our results showed that NaOH, H(2)SO(4), and mild alkali/oxidation pretreatments were useful to rapidly improve the C/N of river water and enhance denitrification.