Temperature-responsive self-contraction nanofiber/hydrogel composite dressing facilitates the healing of diabetic-infected wounds.

Bacterial infections and long-term inflammation cause serious secondary damage to chronic diabetic wounds and hinder the wound healing processes. Currently, multifunctional hydrogels have shown promising effects in chronic wound repair. However, traditional hydrogels only keep the wound moist and protect it from bacterial infection, and cannot provide mechanical force to contract the wound edges to achieve facilitated wound closure.

Discovery of anti-neuroinflammatory agents from 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives by regulating microglia polarization.

Neuroinflammation mediated by microglia activation leads to various neurodegenerative and neurological disorders. In order to develop more and better options for this disorders, a series of 3,4-dihydrobenzo[b]oxepin-5(2H)-one derivatives (BZPs, 6-19) and novel 1,4,5,6-tetrahydrobenzo[2,3]oxepino[4,5-d]pyrimidin-2-amine derivatives (BPMs, 20-33) were synthesized and screened the anti-neuroinflamamtion effects. 3,5-bis-trifluoromethylphenyl-substituted BPM 29 showed more potent anti-neuroinflammatory activity and no toxicity to BV2 microglia cells in vitro.

A nanofiber/sponge double-layered composite membrane capable of inhibiting infection and promoting blood coagulation during wound healing.

Uncontrolled bleeding and bacterial infections cause severe damage to the wounds and remain a clinical challenge. Here, we developed a nanofiber/sponge bilayered composite membrane (QCP) containing quaternized silicone (QP12) and quaternized chitosan (QCS12) by joint approaches of electrospinning and freeze-drying and investigated their potential for wound dressing. The QCP was composed of a sponge (QCC) containing collagen (COL) and QCS12 and a nanofibrous membrane (MQP) containing poly-ε-caprolactone (PCL) and QP12.

Functionalized Electrospun Double-Layer Nanofibrous Scaffold for Wound Healing and Scar Inhibition.

Considerable advances have been made in developing materials that promote wound healing and inhibit scar formation in clinical settings. However, some challenges, such as cumbersome treatment processes and determination of optimal treatment time, remain unresolved. Thus, developing a multifunctional wound dressing with both wound healing and scar inhibition properties is crucial.

Discovery of anti-hepatoma agents from 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine by inhibiting PI3K/AKT/NF-κB pathway activation.

In order to obtain new anti-hepatoma drugs with low toxicity, some 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 4a-t) were synthesized in this study. Many of them showed significant anti-hepatoma effects against HCC cells and low toxicity toward HHL-5 cells. Combined with their anti-hepatoma activity and toxicity, 4-CF-substituted 4k was selected as an effective lead compound.

Trifluoromethyl-substituted 3,5-bis(arylidene)-4-piperidones as potential anti-hepatoma and anti-inflammation agents by inhibiting NF-кB activation.

Some methoxy-, hydroxyl-, pyridyl-, or fluoro-substituted 3,5-bis(arylidene)-4-piperidones (BAPs) could reduce inflammation and promote hepatoma cell apoptosis by inhibiting activation of NF-κB, especially after introduction of trifluoromethyl. Herein, a series of trifluoromethyl-substituted BAPs () were synthesised and the biological activities were evaluated. We successfully found the most potential , which contains three trifluoromethyl substituents and exhibits the best anti-tumour and anti-inflammatory activities.

Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis.

The peritoneum, especially the omentum, is a common site for gastric cancer (GC) metastasis. Our aim was to expound the role and mechanisms of Piezo1 on GC omentum metastasis. A series of functional assays were performed to examine cell proliferation, clone formation, apoptosis, Ca influx, mitochondrial membrane potential (MMP) and migration after overexpression or knockdown of Piezo1.

Discovery of novel NF-кB inhibitor based on scaffold hopping: 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine.

NF-κB is a key signaling pathway molecule linking hepatoma and chronic inflammation. Inhibition of NF-κB activation can alleviate inflammation, and promote hepatoma cell apoptosis. In this study, a series of fluoro-substituted 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 31-57) were synthesized from 3,5-bis(arylidene)-4-piperidones (BAPs, 4-30) based on scaffold hopping.

Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives.

Two fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine (BQA) derivatives, namely 2-amino-4-(2-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (8), and 2-amino-4-(4-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (9), both CHFNO·Cl, were generated by Michael addition reactions between guanidine hydrochloride and the α,β-unsaturated ketones (E)-2-(2-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, CHFO, (6), and (E)-2-(4-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, (7). Because both sides of α,β-unsaturated ketones (6) or (7) can be attacked by guanidine, we obtained a pair of isomers in (8) and (9). Single-crystal X-ray diffraction indicates that each isomer has a chiral C atom and both (8) and (9) crystallize in the achiral space group P2/c.

Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.

Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein "corona" on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces.

A tumor environment responsive doxorubicin-loaded nanoparticle for targeted cancer therapy.

Doxorubicin (DOX) is a potent cancer chemotherapeutic agent, but its clinical use is severely limited by potentially lethal cardiotoxicity. Delivery of DOX by particulate carriers can be an effective way to reduce its distribution in cardiac tissue. In the present study, we developed a self-assembled, tumor-microenvironment-responsive delivery system for DOX.

The autoregulatory feedback loop of microRNA-21/programmed cell death protein 4/activation protein-1 (MiR-21/PDCD4/AP-1) as a driving force for hepatic fibrosis development.

Sustained activation of hepatic stellate cells (HSCs) leads to hepatic fibrosis, which is characterized by excessive collagen production, and for which there is no available drug clinically. Despite tremendous progress, the cellular activities underlying HSC activation, especially the driving force in the perpetuation stage, are only partially understood. Recently, microRNA-21 (miR-21) has been found to be prevalently up-regulated during fibrogenesis in different tissues, although its detailed role needs to be further elucidated.

3,3'-Diindolylmethane ameliorates experimental hepatic fibrosis via inhibiting miR-21 expression.

Background And Purpose: Hepatic fibrosis is a type of liver disease characterized by excessive collagen deposition produced by activated hepatic stellate cells (HSCs), and no appropriate drug treatment is available clinically. The microRNA, miR-21 exhibits an important role in the pathogenesis and progression of hepatic fibrosis. 3,3'-Diindolylmethane (DIM) is a natural autolytic product in plants and can down-regulate miR-21 expression.