Polyhexamethylene guanidine accelerates the macrophage foamy formation mediated pulmonary fibrosis.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

Pulmonary Surfactant Homeostasis Dysfunction Mediates Multiwalled Carbon Nanotubes Induced Lung Fibrosis via Elevating Surface Tension.

Multiwalled carbon nanotubes (MWCNTs) have been widely used in many disciplines and raised great concerns about their negative health impacts, especially environmental and occupational exposure. MWCNTs have been reported to induce fibrotic responses; however, the underlying mechanisms remain largely veiled. Here, we reported that MWCNTs inhalation induced lung fibrosis together with decreased lung compliance, increased elastance in the mice model, and elevated surface tension in vitro. Specifically, MWCNTs increased surface tension by impairing the function of the pulmonary surfactant. Mechanistically, MWCNTs induced lamellar body (LB) dysfunction through autophagy dysfunction, which then leads to surface tension elevated by pulmonary surfactant dysfunction in the context of lung fibrosis. This is a study to investigate the molecular mechanism of MWCNTs-induced lung fibrosis and focus on surface tension. A direct mechanistic link among impaired LBs, surface tension, and fibrosis has been established. This finding elucidates the detailed molecular mechanisms of lung fibrosis induced by MWCNTs. It also highlights that pulmonary surfactants are expected to be potential therapeutic targets for the prevention and treatment of lung fibrosis induced by MWCNTs.

Pulmonary Toxicity Assessment after a Single Intratracheal Inhalation of Chlorhexidine Aerosol in Mice.

Guanidine disinfectants are important chemical agents with a broad spectrum of activity that are effective against most microorganisms. Chlorhexidine, one of the most used guanidine disinfectants, is added to shampoo and mouthwash and applied in medical device sterilization. During the use of chlorhexidine, aerosols with micron particle size may be formed, which may cause inhalation toxicity. To assess the toxicity of inhaled chlorhexidine aerosol, mice underwent the intratracheal instillation of different concentrations of chlorhexidine (0, 0.125%, 0.25%, 0.5%, and 1%) using a MicroSprayer Aerosolizer. The mice were exposed for eight weeks and then sacrificed to obtain lung tissue for subsequent experiments. Histopathology staining revealed damaged lung tissues and increased collagen exudation. At the same time, pulmonary function tests showed that chlorhexidine exposure could cause restrictive ventilatory dysfunction, consistent with pulmonary fibrosis. The results of transcriptome analyses suggest that chlorhexidine may trigger an inflammatory response and promote the activation of pathways related to extracellular matrix deposition. Further, we identified that chlorhexidine exposure might enhance mucus secretion by up-regulating Muc5b and Muc5ac genes, thereby inducing fibrosis-like injury. These findings underscore the need for standardized use of disinfectants and the assessment of their inhalation toxicity.

[Study of interaction between sorbitol and bovine serum albumin by fluorescence spectrometry].

The interaction of sorbitol and bovine serum album (BSA) was studied by fluorescence and ultraviolet absorption spectra. As it is well known to us, the interactional analysis between small molecular drug and biology macromolecule (such as protein, DNA, etc) is one of the important interactional analyses, which can not only offer new biological view but also supply chance for chemist and biochemist to synthesize new drug capable of regulating the biology process effectively. In the present paper, fluorescence spectrophotometry was first employed to study the interaction between BSA and sorbitol. At the same time, the synchronous fluorescence spectroscopy was adopted to review the configuration of BSA influenced by sorbitol, which provides important significance for clinical medication. The results show that sorbitol has strongly quenched the fluorescence of bovine serum albumin in natural physiological condition, the quenching mechanism is a static quenching procedure at different temperatures and drug concentration, and the variational absorption spectra also proves this deduction. At the same time, this article has also examined the influences of sorbitol on the fluorescence quenching of bovine serum albumin at different temperatures and drug concentration. The binding constants and the number of binding sites between sorbitol and BSA were calculated at different temperatures. Furthermore, the enthalpy and entropy changes in the interaction of sorbitol and bovine serum album were also obtained by the equations of Stern-Volmer and Lineweaver-Burk. From the thermodynamic parameters, it can be judged that the primary binding power between sorbitol and BSA is electrostatic force. Moreover, the synchronous fluorescence spectroscopy was applied to examine the effect of sorbitol on the configuration of BSA. The alterative configuration of BSA may be induced by the hydrophobicity environment of tyrosine with the increase in drug concentration. In conclusion, the fluorescence method is highly sensitive and convenient in the study of intermolecular interaction. Further studies in this field will open up the way to applications of biology macromolecule in analytical chemistry and analytical biochemistry.

[Studies on the reaction of balofloxacin with bovine serum albumin].

In the present paper, a fluorescence method was used to study at different pH the fluorescence quenching of bovine serum albumin (BSA) by its interaction with balofloxacin (BLFX). The interaction association constants of BSA and BLFX were determined from a double reciprocal line Weaver-Burk plot. According to the Forster dipole-dipole energy transfer, the distance to be measured between the BLFX and tryptophane is 5.09 nm. From thermodynamical coordination it can be judged that the binding power between BLFX and BSA is electrostatic effect. The effect of BLFX on the conformation of BSA was also analyzed by using synchronous fluorescence spectroscopy.

[Effect of environmental supplementation of iodine on infant mortality and growth in children in Xinjiang, China].

OBJECTIVE: To study the effect of iodine supplementation on infant mortality and growth in Xinjiang. METHODS: Urine iodine, height and head circumference (HC) of children aged 5 years in two townships was measured before and yearly after iodine supplementation of irrigation water. Height and HC were expressed as Z scores (United States children used as the reference group). Neonatal and infant mortality rates were obtained from official records in three counties from 1988 to 1999, and analyzed by a logistic regression model. RESULTS: The odds ratio of infant mortality decreased 56.49% and neonatal mortality 65.71% respectively after iodination; there was no significant difference in the odds ratio of infant or neonatal mortality between experimental and control areas without iodination. In Langru township, the mean height of 5 year-old children increased from 95 cm in 1992 to 106.9 cm in 1998 - 1999, and HC from 48.4 cm to 50.5 cm. Median urine iodine increased from <10 to 176 micro g/L. In Bakechi township, mean height increased from 91 cm in 1993 to 106.5 cm in 1998 - 1999, HC from 48.7 to 49.6 cm, and median urine iodine from 39 to 138 micro g/L. CONCLUSION: In Xinjiang, adequate iodine treatment markedly decreased infant and neonatal mortality, and largely preventing stunting of height and HC in children.