UV C Light from a Light-Emitting Diode at 275 Nanometers Shortens Wound Healing Time in Bacterium- and Fungus-Infected Skin in Mice.

Due to the changes in pathogenic species and the absence of research on topical skin antibiotics, the therapy of skin and soft tissue infections (SSTIs) is facing more and more severe challenges. It is particularly urgent to look for alternative therapies without induction of drug resistance. UV C (UVC) light within the range of 200 to 280 nm is one of the most common techniques used to kill and/or inactivate pathogenic microorganisms. However, the traditional most commonly used wavelength of 254 nm irradiated from a low-pressure mercury lamp is hazardous to human health, being both carcinogenic and damaging to eye tissues, which limits its applications in vivo. This research aimed to investigate the antimicrobial properties and influence of 275-nm UVC light from a light-emitting diode (UVC-LED light) on wound healing time. Five bacteria, three fungi, and scalded-mouse models combined with SSTIs were used to evaluate the antimicrobial effect in vitro and in vivo. 275-nm UVC-LED light inactivated both bacteria and fungi with a very short irradiation time in vitro and induced neither DNA damage nor epidermal lesions in the mice's skin. Furthermore, in mouse models of SSTIs induced by either methicillin-resistant Staphylococcus aureus (MRSA) or Candida albicans, the 275-nm UVC-LED light showed significant antimicrobial effects and shortened the wound healing time compared with that in the no-irradiation group. UVC-LED light at 275 nm has the potential to be a new form of physical therapy for SSTIs. IMPORTANCE As a common clinical problem, the therapy of SSTIs is facing growing challenges due to an increase in the number of drug-resistant bacteria and fungi. UV C (UVC) light sterilization has been widely used in all aspects of daily life, but there are very few reports about in vivo therapy using UVC light. It is well known that prolonged exposure to UVC light increases the possibility of skin cancer. In addition, it is also very harmful for eyes. UV irradiation with 254-nm UVC light can cause corneal damage, like thinning of the corneal epithelial layer, superficial punctate keratitis, corneal erosion, etc. In this study, we focused on looking for a more accessible light source and safer UVC wavelength, and 275-nm UVC LED light was chosen. We investigated its applicability for SSTIs therapy with relative skin safety and expected that it could be used as a new physical therapy method for SSTIs.

Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans.

The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.

Improved anti-hepatocellular carcinoma effect by enhanced Co-delivery of Tim-3 siRNA and sorafenib via multiple pH triggered drug-eluting nanoparticles.

Effective systemic treatment for hepatocellular carcinoma (HCC) remains urgently needed. Sorafenib is the first FDA-approved systemic treatment for HCC. However, individual HCC patents' response to sorafenib varies greatly. How to enhance the anti-HCC effect of sorafenib is still a significant challenge. T cell immunoglobulin mucin-3 (Tim-3) is a newly identified immune checkpoint molecule and a promising target for HCC treatment. Herein, we developed a novel pH-triggered drug-eluting nanoparticle (CC@SR&SF@PP) for simultaneously delivery of Tim-3 siRNA and sorafenib to HCC in situ. By a single emulsification method, a representative HCC targeted-therapeutic drug sorafenib (SF) was encapsulated into the pH-triggered positive-charged mPEG5K-PAE10K (PP) nanoparticles, followed by condensing of negative-charged Tim-3 siRNA. Then, carboxymethyl chitosan (CMCS), an amphoteric polysaccharide with negative charge in the physiological pH and positive charge in the acidic environment of the tumor, was eventually adsorbed onto the surface of nanoparticles. This co-delivery nanoparticle rapidly and specifically accumulated in the tumor site of the liver and enhanced the targeted, specific and multiple release of siRNA and sorafenib. Enhanced Tim-3 siRNA transfected into tumor cells can not only directly inhibit the growth of tumor cells by knock down the expression Tim-3, but also induce the immune response and enhance the recruitment of cytotoxic T cells to kill tumor cells. The following pH-triggered sorafenib release from SF@PP NPs greatly inhibited the tumor proliferation and angiogenesis, resulting in remarkable tumor growth inhibition in a mouse hepatoma 22 (H22) orthotopic tumor model. Thus, co-delivery of Tim-3 siRNA and sorafenib via this novel pH triggered drug-eluting nanoparticle enhances their anti-tumor efficacy. We expect that such combination treatment strategy will have great potential in future clinical applications.

Mucoadhesive nanoparticles-based oral drug delivery systems enhance ameliorative effects of low molecular weight heparin on experimental colitis.

Low molecular weight heparin (LMWH) is reported to have therapeutic action on ulcerative colitis (UC). To facilitate its oral administration and improve the colon-targeting property, LMWH-loaded nanoparticles (TMC-NPs and SA-TMC-NPs) are prepared and evaluated by a series of studies, including their stabilities, drug release profiles, mucosal permeation, mucoadhesion, cytotoxicities, cellular uptake profiles, anticoagulant and anti-inflammatory activities, mucosal healing properties, biosafety and ameliorative effects on experimental colitis. Consequently, oral administration of LMWH-loaded NPs for 5 days perform significant therapeutic effects on mice, which are manifested as improved body weight gains, colon length, DAI score, MPO activity and histological characteristics. Besides, SA-TMC-NPs show better colon-targeting property than TMC-NPs that is demonstrated by lower oral absorption (ATPP 38.95 s) and stronger mucoadhesion (kcps reduces 36.46 %) to inflamed colon tissues. Therefore, TMC-based NPs are proved to be as promising oral colon-targeting drug delivery systems of LMWH and has potential application in UC treatment.

Clinical application of the Innovance D-dimer assay in the diagnosis of acute pulmonary thromboembolism.

Patients with acute pulmonary thromboembolism (APTE) have a high short-term mortality rate. The current study aimed to investigate the use of D-dimer in the diagnosis of APTE in suspected APTE patients. All suspected APTE patients were classified into diagnosis or control groups according to the results of a computed tomography pulmonary angiogram. Mann-Whitney U and Kruskal-Wallis H tests were used to evaluate the association between D-dimer values and APTE. Area under the curve (AUC) values and the Youden Index were used to determine D-dimer cut-off levels for the prediction of APTE. The data of 112 suspected APTE patients (54.8% women; mean age, 70.5 years) were analyzed prospectively. There were no significant differences in age (74.5 vs. 73.5 years, P=0.538) or gender distribution (female ratio 56.5 vs. 53.0%, P=0.847) between the diagnosis and control groups. The incidence of symptoms including dyspnea (67.4 vs. 33.3%; P<0.01), chest distress (47.8 vs. 25.8%; P<0.05) and elevated D-dimer (8.49 vs. 0.97 mg/l; P<0.001) were significantly higher in patients with APTE compared with the control group. D-dimer values >3.32 mg/l fibrinogen equivalent units (FEU) were indicative of APTE and the Youden Index was 0.69. The maximum AUC was 0.87 (95% CI: 0.79-0.92), the sensitivity and specificity were 89.13 and 80.30%, respectively, the positive and negative likelihood ratios were 4.53 and 0.14, respectively, and the positive and negative predictive values were 75.90 and 91.40%, respectively. A D-dimer value <0.60 mg/l FEU was the optimal threshold for excluding APTE diagnosis, with a sensitivity of 100.0% and a specificity of 28.79%. The positive and negative likelihood ratios were 1.40 and 0.00, respectively, and the positive and negative predictive values were 49.50 and 100.00%, respectively. Thus, D-dimer levels, combined with clinical assessment, yield high sensitivity and specificity in diagnosing APTE.