Is the Fractional Laser Still Effective in Assisting Cutaneous Macromolecule Delivery in Barrier-Deficient Skin? Psoriasis and Atopic Dermatitis as the Disease Models.

PURPOSE: Most of the investigations into laser-assisted skin permeation have used the intact skin as the permeation barrier. Whether the laser is effective in improving cutaneous delivery via barrier-defective skin is still unclear. METHODS: In this study, ablative (Er:YAG) and non-ablative (Er:glass) lasers were examined for the penetration of peptide and siRNA upon topical application on in vitro skin with a healthy or disrupted barrier. RESULTS: An enhanced peptide flux (6.9 fold) was detected after tape stripping of the pig stratum corneum (SC). A further increase of flux to 11.7 fold was obtained after Er:YAG laser irradiation of the SC-stripped skin. However, the application of Er:glass modality did not further raise the flux via the SC-stripped skin. A similar trend was observed in the case of psoriasiform skin. Conversely, the flux was enhanced 3.7 and 2.6 fold after treatment with the Er:YAG and the Er:glass laser on the atopic dermatitis (AD)-like skin. The 3-D skin structure captured by confocal microscopy proved the distribution of peptide and siRNA through the microchannels and into the surrounding tissue. CONCLUSIONS: The fractional laser was valid for ameliorating macromolecule permeation into barrier-disrupted skin although the enhancement level was lower than that of normal skin.

Biocompatible Fe3+-TA coordination complex with high photothermal conversion efficiency for ablation of cancer cells.

Near-infrared (NIR) light absorbing nanomaterials, which can convert light to heat energy, have great prospects in biomedical applications. In the current work, Fe3+-TA (Tannic Acid) coordination complex formed by simple mixing of tannic acid and FeCl3 solutions was explored as a novel photothermal agent. Due to the strong absorbance in the near-infrared region induced by the coordination effect between TA molecule and Fe3+ ion, the as-prepared Fe3+-TA complex exhibited excellent photothermal performance with high photothermal conversion efficiency of 77.3% and high photothermal stability. Upon the exposure to Fe3+-TA aqueous dispersions with a concentration of 0.125 mg/mL, the cell mortality of HeLa cells was more than 85% after being irradiated for 10 min under NIR light (808 nm, 6 W cm-2). Besides, the Fe3+-TA complex exhibited ultralow cytotoxicity since only biocompatible tannic acid and iron ions were used as raw materials. Therefore, the merits of simple and convenient fabrication method, high photothermal conversion efficiency and excellent biocompatibility endow the high potential of Fe3+-TA complex as a photothermal agent for biomedical applications.

Liquid Exfoliation of Colloidal Rhenium Disulfide Nanosheets as a Multifunctional Theranostic Agent for In Vivo Photoacoustic/CT Imaging and Photothermal Therapy.

Near-infrared light-mediated theranostic agents with superior tissue penetration and minimal invasion have captivated researchers in cancer research in the past decade. Herein, a probe sonication-assisted liquid exfoliation approach for scalable and continual synthesis of colloidal rhenium disulfide nanosheets, which is further explored as theranostic agents for cancer diagnosis and therapy, is reported. Due to high-Z element of Re (Z = 75) and significant photoacoustic effect, the obtained PVP-capped ReS2 nanosheets are evaluated as bimodality contrast agents for computed tomography and photoacoustic imaging. In addition, utilizing the strong near-infrared absorption and ultrahigh photothermal conversion efficiency (79.2%), ReS2 nanosheets could also serve as therapeutic agents for photothermal ablation of tumors with a tumor elimination rate up to 100%. Importantly, ReS2 nanosheets show no obvious toxicity based on the cytotoxicity assay, serum biochemistry, and histological analysis. This work highlights the potentials of ReS2 nanosheets as a single-component theranostic nanoplatform for bioimaging and antitumor therapy.

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas-Fas ligand and mitochondrial pathway.

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl-2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t-Bid. Osthole treatment also increased the expression of Fas, FADD, TNF-R1, TNF-R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas-Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC.

Natural Humic-Acid-Based Phototheranostic Agent.

Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light-induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near-infrared region. The purified colloidal sodium humate exhibits a high photothermal conversion efficiency up to 76.3%, much higher than that of the majority of state-of-the-art photothermal agents including gold nanorods, Cu9 S5 nanoparticles, antimonene quantum dots, and black phosphorus quantum dots, leading to obvious photoacoustic enhancement in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa tumor is achieved through intratumoral injection. Impressively, sodium humate reveals ultralow toxicity at the cellular and animal levels. This work promises the great potential of humic acids as light-mediated theranostic agents, thus expanding the application scope of traditional humic acids in biomedical field.

Successful treatment of Kasabach-Merritt syndrome with transarterial embolization and corticosteroids.

Kasabach-Merritt syndrome (KMS) refers to the combination of large neonatal vascular tumors and thrombocytopenic coagulopathy. However, a standard treatment regimen for KMS has not yet been established. We report a case of a 6-week-old male infant with life-threatening KMS who was successfully treated with transarterial embolization and corticosteroids. One week after initiating the corticosteroid treatment, his platelet counts recovered, and the lesion growth halted. The approach with corticosteroid therapy resulted in an excellent response that was maintained long enough for us to perform transarterial embolization therapy. The combination of transarterial embolization and corticosteroid therapy should be considered as an option for Kasabach-Merritt syndrome.

[Effects of simvastatin on lipopolysaccharide induced α-subunit epithelial sodium channel mRNA in rat lung alveolar type II epithelial cells].

OBJECTIVE: To study the impact of simvastatin on α-subunit epithelial sodium channel (α-ENaC) mRNA expression in primary culture alveolar typeII (ATII) epithelial cell of rats induced by lipopolysaccharide (LPS) in vitro. METHODS: ATII of primary generation were isolated from adult Sprague-Dawley (SD) rats. The cells were randomly divided into five groups: blank control group, LPS injured group (final concentration of LPS 1 mg/L), simvastatin low and high concentration groups (final concentration of simvastatin 20 µmol/L, 30 µmol/L, respectively), solution control group. Then, after being intervened for 1, 12 and 24 hours, the level of human tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were monitored by enzyme-linked immunosorbent assay (ELISA), and α-ENaC mRNA expression was tested by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After being intervened for 1, 12 and 24 hours, expressions of TNF-α and IL-1ß in LPS injured group were obviously higher than those in blank control group. Expressions of TNF-α and IL-1ß at 1, 12 and 24 hours in simvastatin low concentration group were significantly decreased compared with those in LPS injured group (TNF-α 1 hour: 1178.80±127.43 ng/L vs. 2336.00±170.04 ng/L, 12 hours: 1003.60±59.61 ng/L vs. 2479.80±210.41 ng/L, 24 hours: 695.80±25.24 ng/L vs. 1167.60±132.72 ng/L; IL-ß 1 hour: 285.00±42.60 ng/L vs. 429.60±27.39 ng/L, 12 hours: 238.60±24.12 ng/L vs. 822.20±12.74 ng/L, 24 hours: 213.40±17.87 ng/L vs. 637.60±22.96 ng/L, all P<0.05). Expressions of TNF-α and IL-1ß in high concentration group were decreased more obviously than those in low concentration group (TNF-α 1 hour: 965.60±24.45 ng/L vs. 1178.80±127.43 ng/L, 12 hours: 522.80±16.89 ng/L vs. 1003.60±59.61 ng/L, 24 hours: 252.40±17.64 ng/L vs. 695.80±25.24 ng/L; IL-1ß 1 hour: 225.60±34.44 ng/L vs. 285.00±42.60 ng/L, 12 hours: 190.60±17.64 ng/L vs. 238.60±24.12 ng/L, 24 hours: 152.80±14.70 ng/L vs. 213.40±17.87 ng/L, all P<0.05), but increased compared with those in blank control group. After being intervened for 1 hour, no evident changes were observed in expression of α-ENaC mRNA in all groups. After being intervened for 12 hours and 24 hours, evident decrease in expression of α-ENaC mRNA (A value) was observed in LPS injured group compared with blank control group (12 hours: 0.211±0.021 vs. 0.496±0.027, 24 hours: 0.253±0.030 vs. 0.482±0.030, both P<0.05). Expressions of α-ENaC mRNA in simvastatin low concentration group evidently increased compared with those in LPS injured group (12 hours: 0.363±0.030 vs. 0.211±0.021, 24 hours: 0.309±0.024 vs. 0.253±0.030, both P<0.05). Expressions of α-ENaC mRNA in simvastatin high concentration group increased more obviously compared with those in low concentration group (12 hours: 0.413±0.034 vs. 0.363±0.030, 24 hours: 0.346±0.024 vs. 0.309±0.024, both P<0.05), but decreased compared with blank control group. No evident difference in expressions of all indexes in solution control group was observed compared with those in blank control group. CONCLUSIONS: High dose simvastatin could improve α-ENaC mRNA expression in primary culture ATII epithelial cells of rats. This may act by modulation the level of TNF-α and IL-1ß.