Precisely Controlling the Activation of an Iron-Locked Drug Generator in the Liver Sinusoid to Enhance Barrier Penetration and Reduction of Liver Fibrosis.

Complex physical barriers and the nanomaterial's clearance mechanism in the liver greatly hinder the feasibility of using a conventional liver-targeting nanoplatform to deliver antifibrotic drugs to pathological sites for the treatment of liver fibrosis. Here, a novel drug delivery strategy was designed to overcome drug penetration barriers in a fibrotic liver and cooperated with oral nattokinase (NKase)-mediated antifibrosis therapy as a proof of concept, which relies on the coadministration of a nanosized iron-locked drug generator (named Pro-HAase) and orally absorbed iron chelator deferasirox (DFX). Such a strategy starts from the rapid accumulation of intravenously injected Pro-HAase in the microcapillaries of the fibrotic liver followed by disrupting the polyphenol-iron coordination inside Pro-HAase by DFX, liberating antifibrotic components, including procyanidine (PA) and hyaluronidase (HAase).

Breaking-Down Tumoral Physical Barrier by Remotely Unwrapping Metal-Polyphenol-Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy-Induced Immune Response.

The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO).

Targeting Lysosome for Enhanced Cancer Photodynamic/Photothermal Therapy in a "One Stone Two Birds" Pattern.

Highly immunogenic programmed death of tumor cells, such as immunogenic cell death (ICD) and pyroptosis, strengthens antitumor responses and thus represents a promising target for cancer immunotherapy. However, the development of ICD and pyroptosis inducers remains challenging, and their efficiency is typically compromised by self-protective autophagy. Here, we report a potent ICD and pyroptosis-inducing strategy by coupling combined photodynamic/photothermal therapy (PTT/PDT) to biological processes in cancer cells.

Drug in Therapeutic Polymer: Sinomenine-Loaded Oxidation-Responsive Polymeric Nanoparticles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that frequently involves cartilage damage and the destruction of the bone structure, ultimately resulting in disability and long-term pain. It is clear that overexpression of reactive oxygen species (ROS) and the complex inflammatory microenvironment are the main causes of RA pathogenesis; thereby, the efficacy of any single-drug treatment is limited. Herein, we formulated a therapeutic hyaluronic acid derivative (PAM-HA) with adsorption capacity to the subchondral bone, a long retention time within inflamed joints, and ROS-scavenging capacity, which was used as a drug carrier for realizing the controlled release of sinomenine (Sin) within arthritic joints.

Platycodon grandiflorus polysaccharide regulates colonic immunity through mesenteric lymphatic circulation to attenuate ulcerative colitis.

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms.

A possible but unrecognized risk of acceptable daily intake dose triazole pesticides exposure-bile acid disturbance induced pharmacokinetic changes of oral medication.

Triazole antifungal pesticides work by inhibiting the activity of lanosterol-14-α-demethylase, a member of cytochrome P450 enzymes (CYPs), but this effect is non-specific. Bile acids (BAs) are important physical surfactants for lipids absorption in intestine, and synthesized by CYPs 7A1/27A1. Thus, we presume that triazole exposure might influence the therapeutic effect or safety of oral medication through disturbing the BAs pool, even though the exposure is under an acceptable daily intake (ADI) dose.

Engineering mitochondrial uncoupler synergistic photodynamic nanoplatform to harness immunostimulatory pro-death autophagy/mitophagy.

Generally, autophagy/mitophagy, as a highly conserved lysosomal-based catabolic pathway, compromises the photodynamic therapy (PDT) efficiency by increasing the adaptation of tumor cells toward reactive oxygen species (ROS)-triggered protein damages and mitochondrial destruction. On the other hand, excessively activated autophagy/mitophagy cascades can provoke autophagic cell death and promote the endogenous antigens release of dying cells, thus playing a vital role in initiating the antitumor immune responses. To harness the exquisite immunomodulating effect of pro-death autophagy/mitophagy, we rationally constructed a MnO shell-coated multifunctional porphyrinic metal-organic framework (MOF) to load carbonyl cyanide 3-chlorophenylhydrazone (CCCP).

Engineering a curcumol-loaded porphyrinic metal-organic framework for enhanced cancer photodynamic therapy.

Photodynamic therapy (PDT), a non-invasive and safe treatment, is a clinical promising alternative strategy for certain cancers. Although PDT can trigger tumor specific immunity, the immunosuppressive tumor microenvironment severely limits the efficacy of photodynamic immunotherapy. Curcumol (CUR), extracted from essential oils of traditional Chinese medicine, has potential immune activation effect for cancer immunotherapy.

Heparin-Coated Photosensitive Metal-Organic Frameworks as Drug Delivery Nanoplatforms of Autophagy Inhibitors for Sensitized Photodynamic Therapy against Breast Cancer.

Photosensitive nanosized metal-organic frameworks (nanoMOFs) with a tunable structure and high porosity have been developed recently as nanophotosensitizers (nanoPSs) for photodynamic therapy (PDT). However, the effect of photodynamic therapy is greatly limited by the fast blood clearance and poor tumor retention of the ordinary nanoPSs. Besides, autophagy, a prosurvival self-cannibalization pathway mediated by autolysosomes, was elevated by cytotoxic reactive oxygen species (ROS) produced during PDT.

Metabolic engineering of Escherichia coli for efficient osmotic stress-free production of compatible solute hydroxyectoine.

Compatible solutes are key for the ability of halophilic bacteria to resist high osmotic stress. They have received wide attention from researchers for their excellent osmotic protection properties. Hydroxyectoine is a particularly important compatible solute, but its production by microbes faces several challenges, including low titer/yield, the presence of the byproduct ectoine, and the requirement of high salinity.

CRISPRi-Based Dynamic Control of Carbon Flow for Efficient -Acetyl Glucosamine Production and Its Metabolomic Effects in .

Carbon competition between cell growth and product synthesis is the bottleneck in efficient -acetyl glucosamine (GlcNAc) production in microbial cell factories. In this study, a xylose-induced T7 RNA polymerase-P promoter system was introduced in W3110 to control the GlcNAc synthesis. Meanwhile, an arabinose-induced CRISPR interference (CRISPRi) system was applied to adjust cell growth by attenuating the transcription of key growth-related genes.

Observation of the clinical effect of the combined therapy of zushima tablet and western medicine in the treatment of rheumatoid arthritis and MRI test results.

To evaluate the clinical efficacy of combined therapy of Zushima tablet and western medicine in treatment of rheumatoid arthritis and analyze the MRI test results. A total of 170 patients who had been treated for rheumatoid arthritis at our hospital from August 2016 and June 2018, were enrolled as research objects. They were randomly divided into control group and research group, with 85 patients in each group.

Comparative metabolomic analysis reveals different evolutionary mechanisms for branched-chain amino acids production.

Evolution is a powerful tool for the breeding of microorganisms, while the connection between the changes of intracellular metabolism and different evolution directions is still unclear, which once clarified, will greatly expand the application of evolutionary engineering. We aim to clarify the correlation between metabolism changes and evolution directions in two Corynebacterium glutamicum strains for L-valine and L-leucine overproducing originated from the same parental strain by repeated random mutagenesis and selection. GC-MS metabolomics was performed to identify and quantify intracellular metabolites of the evolved and wild-type C.