Dual tobramycin and docosahexaenoic acid loaded nanoemulsions combating Pseudomonas aeruginosa-induced pulmonary infection.

Pseudomonas aeruginosa (P. aeruginosa) typically forms biofilms in vivo, which exhibit high resistance and complicate eradication efforts. Additionally, persistent inflammation and excessive oxidative stress can lead to severe lung dysfunction, facilitating bacterial colonization and infection. Herein, we prepared oil-in-water (O/W) nanoemulsions (TD-αT NEs) by using PEG5k-block-PCL5k and α-tocopherol to encapsulate tobramycin (TOB). To enhance TOB's drug load, a hydrophobic ion pair (TDIP) composed of TOB and docosahexaenoic acid (DHA) was pre-prepared. TD-αT NEs was not only easily prepared and aerosolized, but stable in both physics and chemistry. The negatively charged TD-αT NEs facilitated penetration through mucus, reaching infection sites. Subsequently, TD-αT NEs permeated biofilms due to their small size and released drugs via lipase-triggered carrier dissociation, aiding in eradicating internal bacteria within biofilms (with a 16-fold reduction in CFU vs. free TOB group). TD-αT NEs simultaneously exerted superior anti-inflammatory effects, reducing levels of pro-inflammatory cytokines (NO, IL-6, IL-8, and TNF-α) while increasing the level of anti-inflammatory cytokine (IL-10). It was achieved through the upregulation of PPAR-γ and downregulation of NF-κB signaling, thus mitigating the lung damage. In addition, TD-αT NEs demonstrated strong antioxidant activity, alleviating the oxidative stress induced by P. aeruginosa. Notably, when administered via inhalation, TD-αT NEs significantly reduced the lung bacterial burden, lung inflammation, and oxidative stress in vivo compared to TOB solution. TD-αT NEs could prove beneficial in treating chronic pulmonary infections induced by P. aeruginosa through a comprehensive strategy, specifically enhancing biofilm eradication, reducing inflammation, and alleviating oxidative stress.

Fetal milieu-simulating hyaluronic acid-dopamine-chondroitin sulfate hydrogel promoting angiogenesis and hair regeneration for wound healing.

Wound regeneration with complete functions and skin appendages is still challenging in wound dressing application. Inspired by the efficient wound healing in the fetal environment, we developed a fetal milieu-mimicking hydrogel for accelerating wound healing simultaneously with hair follicle regeneration. To mimic the fetal extracellular matrix (ECM), which contains high content of glycosaminoglycans, hyaluronic acid (HA) and chondroitin sulfate (CS) were selected to fabricate hydrogels. Meanwhile, dopamine (DA) modification endowed hydrogels with satisfactory mechanical properties and multi-functions. The hydrogel encapsulated atorvastatin (ATV) and zinc citrate (ZnCit), namely HA-DA-CS/Zn-ATV, exhibited tissue adhesion, self-healing capacity, good biocompatibility, excellent anti-oxidant ability, high exudate absorption, and hemostasis property. In vitro results revealed that hydrogels exerted significant angiogenesis and hair follicle regeneration efficacy. In vivo results confirmed that hydrogels significantly promoted wound healing, and the closure ratio reached over 94 % after 14 days of hydrogels-treatment. The regenerated skin exhibited a complete epidermis, dense and ordered collagen. Furthermore, the number of neovessels and hair follicles in the HA-DA-CS/Zn-ATV group were 1.57- and 3.05-fold higher than those of the HA-DA-CS group. Thus, HA-DA-CS/Zn-ATV serves as multifunctional hydrogels for simulating the fetal milieu and achieving efficient skin reconstruction with hair follicle regrowth, exhibiting potential in clinical wound healing.

[Observation on the efficacy of post-stroke dysphagia treated with He's santong acupuncture therapy through surface electromyography: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect on post-stroke dysphagia treated with He's santong (triple promotion) acupuncture therapy through surface electromyography (sEMG). METHODS: A total of 60 patients with post-stroke dysphagia were divided into a routine treatment group and a He's santong acupuncture therapy group, using blocked randomization, 30 cases in each one. In the routine treatment group, the secondary prevention and swallowing rehabilitation training were adopted. In the He's santong acupuncture therapy group, on the base of the treatment as the routine treatment group, weitong (mild promotion, routine acupuncture at bilateral Fengchi ï¼»GB20ï¼½, Fengfu ï¼»GV16ï¼½, Yifeng ï¼»TE17ï¼½, Lianquan ï¼»CV23ï¼½, Jia-lianquan ï¼»Extraï¼½, Fenglong ï¼»ST40ï¼½ and Tongli ï¼»HT5ï¼½, needle retaining for 30 min, 5 treatments a week), wentong (warm promotion, pricking with fire needle at bilateral GB20 and CV23, twice a week) and qiangtong (strong promotion, blood-letting with three-edge needle at Jinjin ï¼»EX-HN12ï¼½, Yuye ï¼»EX-HN13ï¼½ and Yanhoubi ï¼»Extraï¼½, twice a week) treatment was added. The therapy was given consecutively for 4 weeks in each group. The score of fiberoptic endoscopic examination of swallowing (FEES) and Rosenbek-penetration-aspiration scale (PAS), the score of swallowing grading scale, the score of the modified Mann assessment of swallowing ability (MMASA) and the peak amplitude of sEMG were recorded before and after treatment in patients. RESULTS: Compared with before treatment, the score of FEES and PAS after treatment was decreased (P<0.05), the scores of swallowing grading scale and MMASA after treatment were increased in both routine treatment group and He's santong acupuncture therapy group (P<0.05), the peak amplitude of sEMG was increased (P<0.05) in the He's santong acupuncture therapy group and decreased (P<0.05) in the routine treatment group. Compared with the routine treatment group, the score of FEES and PAS was decreased (P<0.05), the scores of swallowing grading scale and peak amplitude of sEMG were increased in the He's santong acupuncture therapy group (P<0.05). CONCLUSION: He's santong acupuncture therapy is obviously effective on post-stroke dysphagia, which may be related to its effects in increasing the contraction of swallowing-related muscles and improving the peak amplitude of hyoid muscle group.