Enhanced antimicrobial activity through the combination of antimicrobial photodynamic therapy and low-frequency ultrasonic irradiation.

The rapid increase of antibiotic resistance in pathogenic microorganisms has become one of the most severe threats to human health. Antimicrobial photodynamic therapy (aPDT), a light-based regimen, has offered a compelling nonpharmacological alternative to conventional antibiotics. The activity of aPDT is based on cytotoxic effect of reactive oxygen species (ROS), which are generated through the photosensitized reaction between photon, oxygen and photosensitizer. However, limited by the penetration of light and photosensitizers in human tissues and/or the infiltration of oxygen and photosensitizers in biofilms, the eradication of deeply located or biofilm-associated infections by aPDT remains challenging. Ultrasound irradiation bears a deeper penetration in human tissues than light and, sequentially, can promote drug delivery through cavitation effect. As such, the combination of ultrasound and aPDT represents a potent antimicrobial strategy. In this review, we summarized the recent progresses in the area of the combination therapy using ultrasound and aPDT, and discussed the potential mechanisms underlying enhanced antimicrobial effect by this combination therapy. The future research directions are also highlighted.

Light intensity alters the effects of light-induced circadian disruption on glucose and lipid metabolism in mice.

Circadian disruption induced by rotating light cycles has been linked to metabolic disorders. However, how the interaction of light intensity and light cycle affects metabolism under different diets remains to be explored. Eighty mice were first randomly stratified into the low-fat diet (LFD, n = 40) or high-fat diet (HFD, n = 40) groups. Each group was further randomly subdivided into four groups (n = 8-12 per group) in terms of different light intensities [lower (LI, 78 lx) or higher intensity (HI, 169 lx)] and light cycles [12-h light:12-h dark cycle or circadian-disrupting (CD) light cycle consisting of repeated 6-h light phase advancement]. Body weight was measured weekly. At the end of the 16-wk experiment, mice were euthanized for serum and pathological analysis. Glucose and insulin tolerance tests were performed during the last 2 wk. The CD cycle increased body weight gain, adipocyte area, glucose intolerance, and insulin resistance of LFD as well as HFD mice under HI but not LI condition. Moreover, the serum and hepatic triglyceride levels increased with LFD-HI treatment, regardless of light cycle. In addition, the CD cycle improved lipid and glucose metabolism under HFD-LI condition. In summary, the detrimental effects of the CD cycle on metabolism were alleviated under LI condition, especially in HFD mice. These results indicate that modulating light intensity is a potential strategy to prevent the negative metabolic consequences associated with jet lag or shift work.NEW & NOTEWORTHY Glucose and lipid homeostasis is altered by the CD cycles in a light-intensity-dependent manner. Lower-intensity light reverses the negative metabolic effects of the CD cycles, especially under HFD feeding. The interaction of light intensity and light cycle on metabolism is independent of energy intake and eating pattern. Glucose metabolic disorders caused by rotating light cycles occur along with compensatory ß-cell mass expansion.

Selective photodynamic inactivation of Helicobacter pylori by a cationic benzylidene cyclopentanone photosensitizer - an in vitro and ex vivo study.

The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm2 532 nm laser, Y1, P1 and P3 at 2.5 µM induced a 3-log10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 µM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 µM led to a complete eradication of H. pylori under the irradiation of 24 J/cm2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues.

Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in Beijing, China: analysis of results from China's top 3 hospital, 2009-2019.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China. METHODS: A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed. RESULTS: A total of 3134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17-79 years). The women aged 35-49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26 and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal. CONCLUSIONS: In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Penetration-enhanced optical coherence tomography angiography with optical clearing agent for clinical evaluation of human skin.

BACKGROUND: Optical coherence tomography angiography (OCTA) is an emerging imaging technique which shows its advantages over visualizing microcirculation with free label. However, its shortcomings in imaging depth limit its development in dermatological field. Nowadays, the newly optical clearing agent (OCA) designed for skin optical imaging demonstrates its potential. In our study, whether this OCA can improve the imaging ability of OCTA in healthy human skin and whether the combination of them is beneficial to compare the lesions and the contralateral normal skins in the patients with port wine stains (PWS) have been investigated. METHODS: Five healthy volunteers and 3 PWS patients were recruited in this study. In terms of healthy people, the opisthenar area which has same structure information as facial skin was taken for investigating the OCA's ability of enhancing OCTA imaging depth on healthy human skin, besides, in order to verifying whether the exists of skin corneum interfere OCA's function, we compared the effect of only using OCA with that of comprehensive using pre-processing skin and OCA. There are one physical removing corneum method by using medical tape to strip opisthenar skin for over 20-time and one chemical way through applying exfoliating cream. For PWS patient, the combining using OCA and OCTA was applied at the lesion area and the contralateral normal area for the purpose of verifying their ability to provide the information of vessels. RESULTS: This novel OCA had excellent efficacy to increase the penetration depth of human opisthenar skin for the OCTA imaging by approximately 0.16 ± 0.03 mm. Pre-processing of stratum corneum with an exfoliating cream or medical tape stripping did not further benefit the penetrating efficacy of the OCA. Moreover, according to a comprehensive analysis of the OCTA images enhanced by the OCA, the PWS lesions usually have larger density and diameter of the vessels which located in deep layers (beyond 0.21 mm) than the contralateral normal skin. CONCLUSIONS: The OCTA imaging depth and contrast were significantly improved by the OCA. The OCA application is a simple and efficient clinical procedure for OCTA enhancement. Moreover, it demonstrated great clinical value to compare the normal skin and the PWS lesions in the patients by the enhanced OCTA imaging.