Search

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar–alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar–alveolar hyperplasia progression, although bronchiolar–alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Humidifier disinfectants (HDs), including polyhexamethylene guanidine phosphate (PHMG-p), are commonly used in Korea to prevent microbial growth. Epidemiological studies show that PHMG-p causes severe lung injury, accompanied by pulmonary inflammation and fibrosis. Several studies have examined humidifier disinfectant-associated lung injuries, but few have examined potential carcinogenic activity of PHMG-p. Our previous studies have shown that PHMG-p can induce lung cancer. However, gene expression changes in squamous cell carcinoma (SCC) caused by PHMG-p have not yet been studied. Objectives: We aimed to determine the PHMG-p-induced changes in transcription levels of genes involved in SCC development and progression in primary bronchial/tracheal epithelial cells (PBTE cells). Results: Genetic alterations induced by PHMG-p were designated as fold change (FC) values of greater than 2 or less than 0.5. RNA sequencing analysis revealed that two genes were upregulated and sixteen genes were downregulated in the short-term PHMG-p exposure group. Fourteen genes were upregulated and 3 genes were downregulated in the long-term PHMG-p exposure group. Conclusion: Our data show that PHMG-p induces genetic changes associated with SCC progression in PBTE cells. [ABSTRACT FROM AUTHOR]

Background: We previously reported the increase in expression of metallothionein1 (MT1) B, MT1F, MT1G, and MT1H after exposure to polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, in human pulmonary alveolar epithelial cells (HPAEpiCs). However, to date, no study has reported the comparative expression of MT1B, MT1F, MT1G, and MT1H in pulmonary cells upon exposure to humidifier disinfectants such as 5-Chloro-2-methyl-3(2H)-isothiazolone with 2-methyl-3(2H)-isothiazolone (CMIT/MIT), oligo(2-(2-ethoxy)ethoxyethyl guanidine chloride) (PGH), benzalkonium chloride (BKC), and sodium dichloroisocyanurate (NaDCC). Objective: The present study aimed to evaluate the expression of MT1B, MT1F, MT1G, and MT1H in HPAEpiCs treated with PHMG-p, CMIT/MIT, PGH, BKC, and NaDCC. Results: Unlike CMIT/MIT, PGH, BKC, and NaDCC, PHMG-p-treated HPAEpiCs showed increased expression of MT1B, MT1F, MT1G, and MT1H. Similarly, exposure to PHMG and PHMG-HCl also induced the expression of MT1B, MT1F, MT1G, and MT1H. Moreover, polyhexamethylene biguanide hydrochloride, a guanidine structure-based chemical, induced the expression of MT1B, MT1F, MT1G, and MT1H. In contrast, polyhexamethylene diisocyanate hydrochloride and guanidine hydrochloride did not induce MT1B, MT1F, MT1G and MT1H. Conclusion: The upregulation of MT1B, MT1F, MT1G, and MT1H in HPAEpiCs is a PHMG-p-specific response in pulmonary cells, and is not induced by CMIT/MIT, PGH, BKC, and NaDCC exposure. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the irreversible ocular diseases that can cause vision loss in some serious cases. Although Triggerfish has been commercialized for monitoring intraocular pressure in glaucoma, there is no smart contact lens to monitor intraocular pressure and take appropriate drug treatment in response to the intraocular pressure levels. Here, we report a precisely integrated theranostic smart contact lens with a sensitive gold hollow nanowire based intraocular pressure sensor, a flexible drug delivery system, wireless power and communication systems and an application specific integrated circuit chip for both monitoring and control of intraocular pressure in glaucoma. The gold hollow nanowire based intraocular pressure sensor shows high ocular strain sensitivity, chemical stability and biocompatibility. Furthermore, the flexible drug delivery system can be used for on-demand delivery of timolol for intraocular pressure control. Taken together, the intraocular pressure levels can be successfully monitored and controlled by the theranostic smart contact lens in glaucoma induced rabbits. This theranostic smart contact lens would be harnessed as a futuristic personal healthcare platform for glaucoma and other ocular diseases. Glaucoma is an irreversible ocular disease that may lead to vision loss. Here the authors develop a theranostic smart contact lens with an intraocular pressure sensor, a flexible drug delivery system, wireless power and communication systems and an application specific integrated circuit chip for both monitoring and control of intraocular pressure in glaucoma induced rabbits. [ABSTRACT FROM AUTHOR]

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)–like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68+ AMφ-like cells were spatially organized on the luminal epithelial surface of alveolar hLOs. Bleomycin-treated alveolar hLOs showed upregulated expression of fibrosis-related markers and extracellular matrix deposits in the alveolar sacs. Alveolar hLOs also showed structural alterations such as excessive tissue fraction under bleomycin treatment. Therefore, we suggest that micro-CT analyzable PSC-derived alveolar hLOs are a promising in vitro model to predict lung toxicity manifestations, including fibrosis. [ABSTRACT FROM AUTHOR]

We aimed to investigate the effect of chronic particulate matter (PM) exposure on bleomycin-induced lung fibrosis in a rat model using chest CT, histopathologic evaluation, and RNA-sequencing. A bleomycin solution was intratracheally administrated to 20 male rats. For chronic PM exposure, after four weeks of bleomycin treatment to induce lung fibrosis, PM suspension (experimental group) or normal saline (control group) was intratracheally administrated for 10 weeks. Chest CT was carried out in all rats, and then both lungs were extracted for histopathologic evaluation. One lobe from three rats in each group underwent RNA sequencing, and one lobe from five rats in each group was evaluated by western blotting. Inflammation and fibrosis scores in both chest CT and pathologic analysis were significantly more aggravated in rats with chronic PM exposure than in the control group. Several genes associated with inflammation and immunity were also upregulated with chronic PM exposure. Our study revealed that chronic PM exposure in a bleomycin-induced lung fibrosis rat model aggravated pulmonary fibrosis and inflammation, proven by chest CT, pathologic analysis, and RNA sequencing. [ABSTRACT FROM AUTHOR]

Our aim was to correlate chest CT and pathologic findings of polyhexamethylene guanidine phosphate (PHMG)-induced lung injuries in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT. A PHMG solution was intratracheally administrated to 40 male rats. Chest CT was carried out in all rats and both lungs were collected for histopathologic evaluation. At 4- and 8-weeks post-instillation, one lobe of the right lung from 3 rats was subjected to RNA sequencing. At least one abnormal CT finding was found in all rats at all weeks. The major CT findings were inflammation, fibrosis, and tumors in the pathologic analysis, where significant changes were observed over time. The lung lesions remained persistent after 8 weeks of PHMG exposure. In the pathologic analysis, the extent/severity of inflammation did not show statistically significant changes over time, whereas the extent/severity of fibrosis increased continuously up to 6 weeks after PHMG exposure and then decreased significantly at 8 weeks. Bronchiolar-alveolar adenomas which have malignant potential were found in 50% of rats at 6 and 8 weeks after PHMG exposure. Also, several genes associated with lung cancer, acute lung injury, and pulmonary fibrosis were detected. Our study revealed that PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. In addition, we showed that PHMG exposure caused lung tumors and genetic alterations according to PHMG exposure under the guidance of CT. [ABSTRACT FROM AUTHOR]

α-SiAlON ceramics have been in use as engineering ceramics in the most arduous industrial environments such as molten metal handling, cutting tools, gas turbine engines, extrusion molds, thermocouple sheaths, protective cover for high-temperature sensors, etc., owing to their outstanding mechanical, thermal and chemical stability. Taking advantage of the intrinsic properties of α-SiAlONs, we investigate, in this paper, the possibility of using the Er-doped α-SiAlON (Er-α-SiAlON) ceramic as a high-temperature sensing material via its unique near-infrared to visible upconversion property. We first use neutron diffraction and density functional theory calculations to study the electronic structure and thermodynamic stability of Er-α-SiAlON. It is found that the interstitial doping of Er stabilizes the α-SiAlON structure via chemical bonds with O-atoms with N:O ratio of 5:2 in the seven-fold coordination sites of the Er3+ ion. Temperature-dependent upconversion emissions are then studied under 980 and 793 nm excitations over a temperature range of 298–1373 K and the fluorescence intensity ratio (FIR) technique has been employed to investigate the temperature sensing behavior. Temperature-dependent Raman behavior is also investigated. We demonstrate that using Er-α-SiAlON as a sensing material, the limit of temperature measurement via the FIR technique can be pushed well beyond 1200 K. [ABSTRACT FROM AUTHOR]

Backgrounds: Hydrofluoric acid (HF) is a highly corrosive acid. The conventional treatment for HF burn is topical application of calcium gluconate (CG). Our study aimed to assess the synergistic effects of natural extracts (Centella asiatica, Portulaca oleracea, and blueberry extracts) in combination with CG in healing HF induced burn wound.Methods: We investigated the effects of different topical CG formulations with natural extracts using cell proliferation assay, western blot, reverse transcription- polymerase chain reaction, human skin equivalent model (HSEM), and mouse model.Results: Topical CG formulations with natural extracts showed better recovery from HF burns shown by greater collagen expression in the dermal fibroblast model, HSEM and mouse model.Conclusion: Our study demonstrated that CG in combination with natural extracts show superior wound healing in treating HF burn compared to CG monotherapy. [ABSTRACT FROM AUTHOR]

In the last decade, the application of nanotechnology techniques has expanded within diverse areas such as pharmacology, medicine, and optical science. Despite such wide-ranging possibilities for implementation into practice, the mechanisms behind nanoparticle skin absorption remain unknown. Moreover, the main mode of investigation has been qualitative analysis. Using interactive segmentation, this study suggests a method of objectively and quantitatively analyzing the mechanisms underlying the skin absorption of nanoparticles. Silica nanoparticles (SNPs) were assessed using transmission electron microscopy and applied to the human skin equivalent model. Captured fluorescence images of this model were used to evaluate degrees of skin penetration. These images underwent interactive segmentation and image processing in addition to statistical quantitative analyses of calculated image parameters including the mean, integrated density, skewness, kurtosis, and area fraction. In images from both groups, the distribution area and intensity of fluorescent silica gradually increased in proportion to time. Since statistical significance was achieved after 2 days in the negative charge group and after 4 days in the positive charge group, there is a periodic difference. Furthermore, the quantity of silica per unit area showed a dramatic change after 6 days in the negative charge group. Although this quantitative result is identical to results obtained by qualitative assessment, it is meaningful in that it was proven by statistical analysis with quantitation by using image processing. The present study suggests that the surface charge of SNPs could play an important role in the percutaneous absorption of NPs. These findings can help achieve a better understanding of the percutaneous transport of NPs. In addition, these results provide important guidance for the design of NPs for biomedical applications. [ABSTRACT FROM AUTHOR]