Enhanced Horizontal Dipole Orientation by Novel Penta-Helicene Anthracene-Based Host for Efficient Blue Fluorescent OLEDs.

Due to the relatively low photoluminescence quantum yield (PLQY) and horizontal dipole orientation of doped films, anthracene-based fluorescent organic light-emitting diodes (F-OLEDs) have faced a great challenge to achieve high external quantum efficiency (EQE). Herein, a novel approach is introduced by incorporating penta-helicene into anthracene, presented as linear-shaped 3-(4-(10-phenylanthracen-9-yl)phenyl)dibenzo[c,g]phenanthrene (BABH) and 3-(4-(10-(naphthalen-2-yl)anthracen-9-yl)phenyl)dibenzo[c,g]phenanthrene (NABH). These blue hosts exhibit minimal intermolecular overlap of π-π stacking, effectively suppressing excimer formation, which facilitates the effective transfer of singlet energy to the fluorescent dopant for PLQY as high as 90%. Additionally, the as-obtained two hosts of BABH and NABH have effectively demonstrated major horizontal components transition dipole moments (TDM) and high thermal stability with glass transitional temperature (Tg) surpassing 188 °C, enhancing the horizontal dipole orientation of their doped films to be 89% and 93%, respectively. The OLEDs based on BABH and NABH exhibit excellent EQE of 10.5% and 12.4% at 462 nm and device lifetime up to 90% of the initial luminance over 4500 h at 100 cd m-2, which has firmly established them as among the most efficient blue F-OLEDs based on anthracene to date to the best knowledge. This work provides an instructive strategy to design an effective host for highly efficient and stable F-OLEDs.

Novel Class of Ultrasound-Triggerable Drug Delivery Systems for the Improved Treatment of Tumors.

The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated a perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering systems.

K237-modified thermosensitive liposome enhanced the delivery efficiency and cytotoxicity of paclitaxel in vitro.

This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL. The morphology of K237-PTX-TSL was observed using a transmission electron microscope. The particle size and potential were measured using a laser particle size analyzer. The phase transition temperature was detected using the differential scanning calorimetry. The Cell Counting Kit-8 assay and flow cytometry were used to evaluate the effects of K237-PTX-TSL on the proliferation and cell cycle of cell lines SKOV-3 and human umbilical vein endothelial cell (HUVEC). The encapsulation efficiency of K237-PTX-TSL was 94.23% ± 0.76%. The particle diameter was 88.3 ± 4.7 nm. K237-PTX-TSL showed a fast release profile at 42 °C, while it was stable at 37 °C. PTX-TSL combined with hyperthermia significantly inhibited the cell proliferation of SKOV-3 cells and HUVECs due to increased cell arrest in the G2/M phase. The half-minimal inhibitory concentration value of K237-PTX-TSL on SKOV-3 cells and HUVECs was 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L, respectively, which were significantly lower than those with PTX-TSL (p < 0.01). K237 modification could increase the targeting efficiency of TSL to cancer cells and vascular endothelial cells, thus resulting in higher cytotoxicities compared with PTX-TSL, which might be a potential formulation for targeting cancer therapy.

A PLGA-PEG-PLGA Thermosensitive Gel Enabling Sustained Delivery of Ropivacaine Hydrochloride for Postoperative Pain Relief.

Postoperative pain is a complex physiological response to disease and tissue injury. Moderate-to-severe pain typically occurs within 48 h after surgery. Amino amide local anesthetics are widely applied to manage postoperative pain, and they have high efficacy, a low risk for addiction and limited side effects. However, these anesthetics also have short half-lives, often necessitating continuous injection to obtain satisfactory pain relief. In the current work, we used a poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA (PLGA-PEG-PLGA) temperature-sensitive gel to deliver a local anesthetic, ropivacaine hydrochloride (RP), to prolong its analgesic effect. We investigated the influence of polymer and drug concentration on gelation temperature and the in vitro drug release rate from the temperature-sensitive gel. RP-loaded PLGA-PEG-PLGA solution is a liquid at room temperature and forms a gel at temperatures slightly lower than body temperature. With regard to the gel's drug release rate, 37.5, 51.3 and 72.6% of RP was released at 12, 24 and 48 h, respectively. This in vitro drug release profile conformed to the Higuchi equation. To assess pain control efficacy when using the gel, we evaluated the mechanical paw withdrawal reflex threshold, thermal pain threshold and incision cumulative pain scores in a rat incisional model. The results showed that the anti-pain effect of a single injection of RP-loaded gel at the incision site lasted for 48 h, which is significantly longer than the effect produced by injection of RP solution alone. The use of RP-loaded thermosensitive gels could provide a promising method for managing postoperative pain.

Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer.

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

Ritonavir-induced hepatotoxicity and ultrastructural changes of hepatocytes.

To investigate the effect of ritonavir on hepatocyte proliferation, we detected the change of cleaved caspase-3 expression level in the hepatocytes. Furthermore, the morphological and ultrastructural changes of hepatocytes derived from RTV-treated mice have been observed. The results showed that ritonavir can evidently inhibit hepatocyte proliferation and increase cleaved caspase-3 expression level. Under the electron microscope, chromatin margination, mitochondrial cristae disappearance, karyopyknosis and cytoplasmic vacuolization can be observed in the hepatocytes of mice treated with ritonavir. In conclusion, the mechanism of ritonavir's hepatotoxicity is that it induces apoptosis of hepatocytes via the caspase-cascade system.

The protective effect of curcumin on hepatotoxicity and ultrastructural damage induced by cisplatin.

We investigate the protective effect of curcumin (CU) on the hepatic ultrastructural damage induced by cisplatin in mice. 18 adult Kunming mice were randomly divided into normal saline (NS) group, cisplatin treatment group (CP) and CU + CP group (n = 6 for each group). Mice in control group and CP group were administered with NS (20 mL/kg/day) and CU + CP group were i.p injected with CU (200 mg/kg/day) for 10 days. Then cisplatin (50 mg/kg/day) was injected in mice of CP group and CU + CP group, while those in control group were given the same volume of NS. Five days after injection all mice were killed and liver dissected. The hepatic morphological structures were observed under light microscope and transmission electron microscope. The results indicated that CU alleviated the hepatic histopathological damages induced by cisplatin, which included declined body weight, vacuolated cytoplasm and blurred liver trabecular structure. Moreover, no hepatic ultrastructural damages were observed in the CU protective group with condensed and marginated nuclear chromatin, bile canaliculi outstreched and bile deposited.

TNF-α mediated increase of HIF-1α inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI).

Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-α) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-α, 0.1 to 8 ng/mL TNF-α exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-α group (control group). However, 10 ng/mL and 100 ng/mL TNF-α dramatically inhibited the viability of A549 cells compared with the control group (*p<0.05). Monolayer cell permeability assay results indicated that A549 cells incubated with 10 ng/mL TNF-α for 24 hours displayed significantly increased cell permeability (*p<0.05). Moreover, the inhibition of VASP expression increased the cell permeability (*p<0.05). Pretreating A549 cells with cobalt chloride (to mimic a hypoxia environment) increased protein expression level of hypoxia inducible factor-1α (HIF-1α) (*p<0.05), whereas protein expression level of VASP decreased significantly (*p<0.05). In LPS-induced ALI mice, the concentrations of TNF-α in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1α protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**p<0.001), whereas the VASP protein expression level decreased significantly (**p<0.01). Taken together, our data demonstrate that HIF-1α acts downstream of TNF-α to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier.

The effects of X-ray irradiation on the proliferation and apoptosis of MCF-7 breast cancer cells.

To investigate the effects of X-ray irradiation on the proliferation and apoptosis of MCF-7 breast cancer cells; MCF-7 breast cancer cells were irradiated with X-ray. After irradiation, morphological changes and growth inhibition rate of the irradiated cells were observed under an inverted microscope. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the proliferation of the irradiated MCF-7 cells. Transmission electron microscope was used to observe the morphology and ultrastructure of the irradiated MCF-7 cells. Western blotting was used to analyze the expression level of apoptosis-related protein caspase-3. Our results showed, at 48 h after the irradiation (0 Gy and 8 Gy), cells oval in shape, cell shrinkage or swelling and partial formation of debris under inverted microscope; as well as cytoplasmic vacuolization or inspissation, increased electron density of cytoplasm, structural damage of organelles, blurred mitochondrial cristae and chromatin margination under transmission electron microscopy; the survival rate of MCF-7 cells in X-ray group was 17.3% lower than that in control group (0 Gy) (p < 0.001); while caspase-3 expression increased evidently in X-ray group compared with control group (0 Gy) (p < 0.05). In conclusion, X-ray irradiation can inhibit the proliferation of MCF-7 cells and induce apoptosis through increasing caspase-3 expression.