The treatment of human immunodeficiency virus (HIV) infection is notoriously difficult due to the ability of this virus to remain latent in the host's CD4
T cells. Histone deacetylases (HDACs) ...interfere with DNA transcription in HIV-infected hosts, resulting in viral latency. Therefore, HDAC inhibitors can be used to activate viral transcription in latently infected cells, after which the virus can be eliminated through a shock-and-kill strategy. Here, a drug delivery system is developed to effectively deliver HDAC inhibitors to latent HIV-infected cells. Given that the efficacy of HDAC inhibitors is reduced under hypoxic conditions, oxygen-containing nanosomes are used as drug carriers. Oxygen-containing nanosomes can improve the efficiency of chemotherapy by delivering essential oxygen to cells. Additionally, their phospholipid bilayer structure makes them uniquely well-suited for drug delivery. In this study, a novel drug delivery system is developed by taking advantage of the oxygen carriers in these oxygen nanosomes, incorporating a multi-drug strategy consisting of HDAC inhibitors and PKA activators, and introducing CXCR4 binding peptides to specifically target CD4
T cells. Oxygen nanosomes with enhanced targeting capability through the introduction of the CXCR4 binding peptide mitigate drug toxicity and slow down drug release. The observed changes in the expression of p24, a capsid protein of HIV, indirectly confirm that the proposed drug delivery system can effectively induce transcriptional reactivation of HIV in latent HIV-infected cells.
•Hypericin and laser irradiation induced anaplastic thyroid cancer cell death.•Hypericin-mediated photodynamic therapy promoted ROS generation and mitochondrial damage in cells.•Hypericin with laser ...irradiation prevented anaplastic thyroid cancer growth in the mouse.
Hypericin (HYP) extracted from St. John’s wort (Hypericum perforatum L.) is a natural photosensitizer in clinical photodynamic therapy (PDT). PDT is one of the powerful methods for cancer treatments because of its excellent tumoritropic characteristics and photosensitizing properties. However, limited reports on the efficacy of PDT on anaplastic thyroid cancer (ATC) have been published. Especially HYP-associated PDT has not been investigated in vitro and in vivo. In this study, we evaluated the effect of HYP for PDT against FRO ATC cells.
The activities of HYP-assisted PDT were investigated in ATC cells. The ATC FRO cells were treated with a combination of HYP dose and laser power. The viability of FRO cells was measured by MTT assay, and Trypan blue staining was performed to monitor cell death. Detection reactive oxygen species (ROS) and mitochondrial membrane potential after HYP-assisted PDT were analyzed by confocal microscopy. For in vivo study, FRO cells were injected into nude mice. After intravenous injection of HYP, Laser was irradiated and nude mice were monitored in Day 4, 7, 14.
The rate of FRO cell death was increased by applying HYP dose and laser power dependent. Moreover, HYP and laser irradiation induced FRO cell death was mediated by the intracellular ROS generation and mitochondrial damage. Finally, the HYP-assisted PDT eliminated FRO cell tumor from the mouse in vivo. These data demonstrate that HYP could be an effective photosensitizer for human ATC therapy.
To minimize thermal injury, the current study evaluated the real-time temperature monitoring with a proportional-integrative-derivative (PID) controller during 980-nm photothermal treatment with a ...radially-diffusing applicator. Both simulations and experiments demonstrated comparable thermal behaviors in temperature distribution and the degree of irreversible tissue denaturation. The PID-controlled application constantly maintained the pre-determined temperature of 353 K (steady-state error = < 1 K). Due to constant energy delivery, coagulation volumes linearly increased up to 1.04 ± 0.02 cm(3) with irradiation time. Integration of temperature feedback with diffuser-assisted photothermal treatments can provide a feasible therapeutic modality to treat pancreatic tumors in an effective manner.
The present study proposes an innovative opto-chemical treatment using a basket-integrated optical device (BIOD) to disinfect mature bacterial biofilm on endoscope channels. A BIOD was designed to ...position an optical diffuser on the central axis of an endoscope channel and to distribute laser light concentrically to the bacterial biofilm on the channel surface. To apply thermal damage and oxidative stress to the bacterial biofilm, a low concentration of a crosslinking agent (glutaraldehyde ~0.5%) was combined with 808 nm infrared (IR) and 405 nm blue (BL) laser lights. The applied irradiances of IR and BL were 10 W/cm2 and 1.6 W/cm2 for Teflon channel model and 20 W/cm2 and 3.2 W/cm2 for a clinical model, respectively. Individual irradiation of either IR or BL for 180 s induced the maximum temperatures of 62 ± 2 °C and 53 ± 3 °C on the biofilm, respectively. The simultaneous opto-chemical treatment reduced a significant population of the bacterial biofilms (7.5-log10 for Staphylococcus aureus and 7.1-log10 for Pseudomonas aeruginosa), which were 2.9-fold and 3.9-fold higher than that of the standard treatment with 2% glutaraldehyde (GA) solution, respectively. The proposed opto-chemical disinfection method can help reduce multi-drug resistant bacteria and prevent cross-infection during the clinical usage of a flexible endoscope.
•A novel opto-chemical treatment can disinfect opportunistic respiratory pathogens in a clinical endoscope.•Glutaraldehyde, infrared, and blue lights were simultaneously combined for collective biofilm disinfection.•Laser lights were delivered concentrically and circumferentially into the endoscope.•Thermal denaturation and oxidative stress led to rapid and effective disinfection of biofilm in an endoscope.
This study aims to demonstrate the feasibility of cylindrical interstitial laser ablation (CILA) in porcine pancreatic tissue to develop a EUS-guided PC ablation technique with enhanced safety. A ...diffusing applicator created a uniformly symmetrical laser ablation in pancreatic tissue. Ex vivo tests presented that both ablation thickness and volume increased linearly with the applied power (R 2 = 0.96 and 0.90, respectively) without carbonization and fiber degradation. The numerical simulations matched well with the experimental results in terms of temperature development and thermal damage (deviation of ≤ 15%). In vivo tests with EUS confirmed easy insertion and high durability of the diffusing applicator. EUS-guided CILA warranted a feasible therapeutic capacity of ablating in vivo pancreatic tissue. The proposed EUS-guided CILA can be a feasible therapeutic approach to treat PC with predictable thermal ablation and enhanced safety.
The formation of a frustrated Lewis pair consisting of sodium hydride (Na+H−) and a framework‐bound hydroxy proton O(H+) is reported upon H2 treatment of zeolite NaY loaded with Pt nanoparticles ...(Ptx/NaY). Frustrated Lewis pair formation was confirmed using in situ neutron diffraction and spectroscopic measurements. The activity of the intrazeolite NaH as a size‐selective catalyst was verified by the efficient esterification of acetaldehyde (a small aldehyde) to form the corresponding ester ethyl acetate, whereas esterification of the larger molecule benzaldehyde was unsuccessful. The frustrated Lewis pair (consisting of Na+H− and O(H+)) generated within zeolite NaY may be a useful catalyst for various catalytic reactions which require both H− and H+ ions, such as catalytic hydrogenation or dehydrogenation of organic compounds and activation of small molecules.
In den Poren: Frustrierte Lewis‐Paare (FLPs) mit Natriumhydrid (Na+H−) und gerüstgebundenen Hydroxyprotonen O(H+) bilden sich im Inneren der Nanoporen von Platinnanopartikel‐beladenem Zeolith NaY nach Behandlung mit H2 bei ca. 400 K. FLP‐haltige Zeolithe könnten sich für größen‐ und formselektive ionische Hydrierungen eignen.
Primary hepatocellular carcinoma (HCC) and colon carcinoma are two of the most common clinical malignancies along with high morbidity and mortality. As low-power laser irradiation (LPLI) can induce ...cytotoxicity or cell apoptosis on several types of hyperplasia, LPLI may be a potential alternative treatment for gastroenterological cancers. The current in vitro study focused on LPLI-induced apoptosis and mechanism after 532-nm laser irradiation on two different carcinoma cells. Squamous cell carcinoma (VX2) and murine colon carcinoma (CT26) cells were cultured to test the feasibility of LPLI. The applied fluence varied from 0 to 600 J/cm
2
. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide analysis, fluorescence imaging, wound healing assay, and cell apoptosis tests were performed 24 h post-irradiation to monitor cellular responses. The current results demonstrated a dose-dependent stimulatory effect of LPLI on the cell viability, migration, and apoptosis of VX2 and CT26 cells. The therapeutic fluence of 600 J/cm
2
induced statistically significant inhibition in cell viability. Both the wound healing assay and the cell apoptosis tests confirmed that LPLI with high fluences could inhibit cell migration as well as induce cell apoptosis. The current findings demonstrate that LPLI might be a potential treatment for the carcinoma cells. Further studies will be performed to evaluate the feasibility of LPLI in in vivo tumor models.
Focused ion beam (FIB) systems are one of the most important pieces of equipment in nanoscale machining, and can etch material and deposit 3-D nanoscale structures with high aspect ratios. However, ...despite considerable research effort, a definitive method for evaluating the reliability of FIB systems had not been developed. In this paper, we propose a reliability assessment method that utilizes fabricated nanopatterns. Since the characteristics of a FIB system are included in the nanopatterns, these can be used to assess its reliability. We suggest items and nanopatterns that can be applied to the reliability assessment tests. To determine the suitability of the proposed method, we fabricated several nanopatterns using different FIB systems and measured them under a scanning electron microscope to compare the actual and designed dimensions. The results showed that the proposed method is suitable for assessing the reliability of FIB systems.
Pancreatic cancer (PC) is a leading cause of cancer death and its incidence and mortality have shown an increasing trend. Despite improvements in outcomes, another treatment option is required for ...PC. Laser ablation (LA) has been evaluated for the treatment of various types of cancer. The aim of this study was to assess the safety and feasibility of a novel cylindrical light diffuser in a xenograft model of PC. This study was performed using a customized high-power laser system. PANC-1 cells and BALB/c mice were used for experiments at a laser power of 5 W for 40 to 200 s at five different energy levels (
n
= 30). There was no acute bleeding or major complication. Using the cylindrical light diffuser, tumors were irradiated with similar size in each energy group. A correlation between laser dose and tumor necrosis was observed. Pearson’s correlation for the relation between the amount of necrosis area and laser ablation energy on day 3 was 0.78 (
p
< 0.01). No statistical difference of necrosis area was exhibited when the necrosis area of each harvested tumor analyzed by dividing into 5 specimens for each energy. The study demonstrates that LA treatment using a cylindrical light diffuser induced remarkable tumor necrosis at histopathologic examinations. Laser ablation dosage and tumor response were strongly correlated, and the ablation procedure resulted in homogeneous tissue necrosis. No adverse event was encountered. These findings suggest that the devised cylindrical light diffuser offers a safe and effective means of treating pancreatic cancer.
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