An Engineered Protein-Au Bioplaster for Efficient Skin Tumor Therapy.

Melanoma is the most lethal malignancy in skin cancer and may occur at any site and express melanocytes. Due to malignant melanoma's invasion and migration nature, conventional therapies make it challenging to remove the whole tumor tissue while undertaking the high risks of tumor recurrence. Regarding the emerging targeted therapies and immunotherapy, drug resistance and low immunotherapeutic activity remain significant challenges. It is thus becoming urgently important to develop alternative strategies for melanoma therapy. Herein, a novel bifunctional protein-based photothermal bioplaster (PPTB) is developed for non-invasive tumor therapy and skin tissue regeneration. The complexation of adhesive protein and gold nanorods (GNRs) endow the obtained PPTB with good biocompatibility, controllable near-infrared (NIR) light-mediated adhesion performance, and high photothermal performance. Therefore, the PPTB bioagent facilitates skin adhesion and effectively transfers heat from skin to tumor. This behavior endows PPTB capability to eradicate skin tumors conveniently. Thus, the assembly strategy enables this hybrid bioplaster to hold great potential for skin-related tumor treatment.

Trichostatin A regulates fibro/adipogenic progenitor adipogenesis epigenetically and reduces rotator cuff muscle fatty infiltration.

Rotator cuff (RC) muscle fatty infiltration (FI) is an important factor that determines the clinical outcome of patients with RC repair. There is no effective treatment for RC muscle FI at this time. The goal of this study is to define the role Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor in regulating muscle fibro/adipogenic progenitors (FAPs) adipogenesis and treating muscle fatty degeneration after massive RC tears in a mouse model. We hypothesize that TSA reduces muscle FI after massive RC tears. HDAC activity was measured in FAPs in RC muscle after tendon/nerve transection or sham surgery. FAPs were treated with TSA for 2 weeks and FAP adipogenesis was evaluated with perilipin and Oil Red O staining, as well as reverse transcript-polymerase chain reaction for adipogenesis-related genes. About 0.5 mg/kg TSA or dimethyl sulfoxide was administered to C57B/L6 mice with massive rotator cuff tears through daily intraperitoneal injection for 6 weeks. Supraspinatus muscles were harvested for biochemical and histology analysis. We found that FAPs showed significantly higher HDAC activity after RC tendon/nerve transection. TSA treatment significantly reduced HDAC activity and inhibited adipogenesis of FAPs. TSA also abolished the role of bone morphogenetic protein-7 in inducing FAP adipogenesis and promoted FAP brown/beige adipose tissue (BAT) differentiation. TSA injection significantly increased histone H3 acetylation and reduced FI of rotator cuff muscles after massive tendon tears. Results from this study showed that TSA can regulate FAP adipogenesis and promote FAP BAT differentiation epigenetically. HDAC inhibition may be a new treatment strategy to reduce muscle FI after RC tears and repair.

Dandelion Extract Alleviated Lipopolysaccharide-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells.

In practical dairy production, cows are frequently subjected to inflammatory diseases, such as high-grain diet-induced subacute ruminal acidosis (SARA) as well as mastitis and metritis. Under the circumstances, lipopolysaccharide (LPS) induces oxidative stress within the cow and in the mammary epithelial cells. It has implications in practical production to alleviate oxidative stress and to optimize the lactational function of the mammary epithelial cells. This study thus aimed to investigate the antioxidative effects of dandelion aqueous extract (DAE) on LPS-induced oxidative stress and the mechanism of DAE as an antioxidant to alleviate oxidative stress through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the bovine mammary epithelial cell line MAC-T cells. The cells were cultured for 48 h in six treatments including control (without LPS and DAE), LPS (100 ng/mL), DAE10 (100 ng/mL LPS and 10 µg/mL DAE), DAE50 (100 ng/mL LPS and 50 µg/mL DAE), DAE100 (100 ng/mL LPS and 100 µg/mL DAE), and DAE200 (100 ng/mL LPS and 200 µg/mL DAE), respectively. The results showed that cell viability was reduced by LPS, and the adverse effect of LPS was suppressed with the supplementation of DAE. Lipopolysaccharide-induced oxidative stress through enhancing reactive oxygen species (ROS) production, resulted in increases in oxidative damage marker concentrations, while 10 and 50 µg/mL DAE alleviated the LPS-induced oxidative stress via scavenging cellular ROS and improving antioxidant enzyme activity. The upregulation of antioxidative gene expression in DAE treatments was promoted through activating the Nrf2 signaling pathway, with DAE at a concentration of 50 µg/mL exhibiting the highest effect. Overall, DAE acted as an effective antioxidant to inhibit LPS-induced oxidative stress and as a potential inducer of the Nrf2 signaling pathway.

A study on the puncture method of extrapedicular infiltration anesthesia applied during lumbar percutaneous vertebroplasty or percutaneous kyphoplasty.

Extrapedicular infiltration anesthesia (EPIA) was reported for percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) and provided good local anesthetic effects. Because of differences in anatomical morphology at each lumbar level, the puncture method of EPIA is not uniform in each lumbar vertebrae. To accurately insert the anesthetic needle into the extrapedicular region, we researched the puncture method of EPIA at each lumbar level.We retrospectively analyzed computed tomography (CT) images in 230 patients with lumbar osteoporotic fractures, including 59 L1 fractures, 54 L2 fractures, 50 L3 fractures, 36 L4 fractures, and 31 L5 fractures. The puncture of EPIA was simulated in every fractured vertebrae through CT, and the skin puncture point, puncture direction, and puncture depth of the anesthetic needle were observed. These specific parameters were the distance from the skin puncture point to the superior border of the pedicle projection on the skin (distance AD), distance from the skin puncture point to the lateral border of the pedicle projection on the skin (distance BC), sagittal section angle (SSA), transverse section angle (TSA), and depth of EPIA.As the lumbar ordinal number increased, the SSA, distance AD, TSA, and distance BC for each lumbar level gradually increased, and the puncture depth gradually decreased, all these parameters showed significant differences among the 5 lumbar levels (P < .001). The recommended puncture methods for EPIA at each lumbar level, including distance AD, distance BC, SSA, and TSA, were as follows: in L1, 4 mm, 8 mm, 9° and 8°; in L2, 6 mm, 10 mm, 11° and 10°; in L3, 9 mm, 13 mm, 12° and 12°; in L4, 12 mm, 18 mm, 16° and 18°; and in L5, 20 mm, 26 mm, 24° and 24°. The depth of EPIA was 13 mm in L1-L3 and 11 mm in L4-L5.By confirming the skin puncture point and puncture direction of the anesthetic needle, from an anatomical perspective, EPIA is feasible for lumbar PVP (PKP).

Trillium tschonoskii maxim saponin mitigates D-galactose-induced brain aging of rats through rescuing dysfunctional autophagy mediated by Rheb-mTOR signal pathway.

During the expansion of aging population, the study correlated with brain aging is one of the important research topics. Developing novel and effective strategies for delaying brain aging is highly desired. Brain aging is characteristics of impaired cognitive capacity due to dysfunctional autophagy regulated by Rheb-mTOR signal pathway in hippocampal tissues. In the present study, we have established a rat model with brain aging through subcutaneous injection of D-galactose (D-gal). Upon the intervention of Trillium tschonoskii Maxim (TTM) saponin, one of bioactive components from local natural herbs in China, the learning and memory capacity of D-gal-induced aging rats was evaluated through Morris water maze test, and the regulation of Rheb-mTOR signal pathway and functional status of autophagy in hippocampal tissues of D-gal-induced aging rats was explored by Western blot. TTM saponin revealed an obvious function to improve learning and memory capacity of D-gal-induced aging rats through up-regulating Rheb and down-regulating mTOR, thereby rescuing dysfunctional autophagy to execute anti-aging role. Meanwhile, this study confirmed the function of TTM saponin for preventing and treating brain aging, and provided a reference for the development and utilization of natural products in health promotion and aging-associated disease treatment.