Investigations of Laser-Assisted Renal Denervation for Treatment of Resistant Hypertension.

BACKGROUND AND OBJECTIVES: Renal denervation (RDN) is an emerging surgical treatment for resistant hypertension. However, the current RDN using radiofrequency can cause undesirable thermal damage to the medial and luminal layers due to direct contact between the arterial lumen and energy source. The aim of this study is to evaluate the feasibility of the new laser-assisted RDN by exploring the potential treatment conditions. METHODS: For ex vivo testing, six different treatment conditions (10 and 20 W applied for delivery of 300, 450, and 600 J) were tested on the porcine liver and renal artery (RA) by using a continuous wave 1064 nm laser wavelength. The ablated area in the liver tissue was measured to estimate the extent of the coagulated area. Histological evaluation was performed on the treated RA tissues to confirm the extent of thermal nerve damage. RESULTS: The ablated depth, length, and area in the liver tissue increased with laser power and total energy. According to the histological results, 20 W groups yielded more significant damage to the RA nerves than 10 W groups at the total energy of 300 J (0.0 ± 0.0 mm for 10 W vs. 2.9 ± 1.0 mm for 20 W), 450 J (1.9 ± 0.6 mm for 10 W vs. 6.8 ± 1.5 mm for 20 W), and 600 J (2.9 ± 0.4 mm for 10 W vs. 7.3 ± 0.8 mm for 20 W). The treated RA exhibited insignificant medial injury in depth (medial thinning ≤ 25%), and no difference in the medial thinning was found among the six groups (p = 0.4). CONCLUSION: The current study demonstrated that the 1064 nm laser at 20 W with delivery of 450 J could effectively damage the RA nerves with no or minimal injury to the surrounding tissue. The proposed laser-assisted RDN may enhance physiological effects with insignificant complications in in vivo situations. Further in vivo studies will be conducted to validate the current findings by evaluating the extent of blood pressure reduction and norepinephrine changes after the laser-assisted RDN on a large animal model.

Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer.

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.

Photo-triggered caffeic acid delivery via psyllium polysaccharide- gellan gum-based injectable bionanogel for epidermoid carcinoma treatment.

Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm2 for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light.

Cellulose nanofibrils reinforced chitosan-gelatin based hydrogel loaded with nanoemulsion of oregano essential oil for diabetic wound healing assisted by low level laser therapy.

Diabetic foot ulcers are imperfections in the process of wound healing due to hyperglycemic conditions. Here, a nanoemulgel fabricated with oregano essential oil nanoemulsion, assisted by low-level laser therapy, was investigated for its efficacy in diabetic wound healing. A hydrogel- based healing patch, fabricated using biological polymers namely chitosan and gelatin and, polyvinyl pyrollidone. The hydrogel was reinforced with cellulose nanofibrils for enhanced stability and barrier properties. Nanoemulsion of oregano essential oil, with an average particle size of 293.7 ± 8.3 nm, was prepared via homogenization with chitosan as the coating agent. Nanoemulsion impregnated hydrogel, termed as the nanoemulgel, was assessed for its physio-mechanical properties and healing efficiency. The strong linkages in nanoemulgel demonstrated its large swelling capacity, high mechanical strength, and maximum thermal stability. The optimized conditions for low-level laser therapy using 808 nm were 1 W. cm-2 and 5 min. The optimized drug concentration of 128 µg. mL-1 exhibited viability of NIH/3 T3 fibroblasts as 75.5 ± 1.2 % after 24 h. Cell migration assay demonstrated that dual therapy facilitated wound healing, with a maximum closure rate of 100 % at 48 h. In vivo results revealed the rapid healing effects of the dual therapy in diabetic rat models with foot ulcers: a maximum healing rate of 97.5 %, minimum scar formation, increased granulation, enhanced reepithelialization, and a drastic decrease in inflammation and neutrophil infiltration within the treatment period compared to monotherapy and control. In summary, the combinatorial therapy of nanoemulgel and low-level laser therapy is a promising regimen for managing diabetic foot ulcers with a rapid healing effect.

Effect of dual-optical pulses with temporal energy distribution on laser ablation performance in in vivo zebrafish model.

A Q-switched laser system has been used in a single-pulse mode for skin melasma treatments because of instant heat deposition in the target. Despite the efficient ablation of the melanophores in the skin, the single, high-fluence pulse often causes undesirable damage to the surrounding tissue, leading to high recurrence rates. This study aims to investigate the feasibility of dual-optical pulses with a temporal energy distribution on the melasma treatment in in vivo zebrafish models in comparison to that of the single optical pulse. Based on the optical detection, the dual-optical pulses had a temporal energy distribution ratio of 4:1 and an interval of 61 µs between the two consecutive pulses. According to the histological analysis, the dual pulses removed melanophores and induced a few apoptotic nuclei with minimal recurrence. This study demonstrated that the feasibility of dual-optical pulses (energy ratio = 4:1) could enhance the laser ablation performance in vivo.

Combinatorial prophylactic effect of phlorotannins with photobiomodulation against tracheal stenosis.

Several conventional treatments are used to manage tracheal stenosis after intubation and surgical procedures; however, patients are at risk of restenosis because of the absence of effective preventative therapy. In this study, we evaluate the biomodulatory effect of PT-combined blue light (BL) PBM in tracheostomal stenosis-induced animal models. The PT-combined BL group showed a significant decrease in the fibrotic protein synthesis by downregulating the release of stenosis-triggering fibrotic signals, without cytotoxicity or thermal damage. Moreover, the combined treatment ameliorated excessive granulation and collagen formation, and consequently preserved the opening of the tracheostoma ten days after fenestration. The current study demonstrated the biomodulatory effect of PT-combined BL on human tracheal fibroblasts and tracheal fenestration rodent models. Hence, PT-combined BL has the potential to be an effective preventative treatment for tracheal stenosis but also as an alternative option for fibrotic disorders.