Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

[Investigation on injury of liver and kidney among the workers exposed to terephthalic acid, ethylene glycol and(or) dowtherm A].

OBJECTIVE: To study injury of liver and kidney among the workers exposed to terephthalic acid(TPA), ethylene glycol(EG) and(or) dowtherm A(DOW), and research for early biological monitoring indexes. METHODS: By using the method of occupational epidemiology, an investigation of industrial hygiene in a chemical fibre corporation was carried out and the changes of the liver and kidney functions were analyzed among the workers who had been exposed to TPA, EG, DOW. RESULTS: The values of serum gamma-glutamyl traspetidase(GGT) and total bile acid(TBA) in TPA + EG + DOW group men were (35.45 +/- 16.09) U/L, (10.29 +/- 6.76) mumol/L respectively and the values of serum alanine transaminase(ALT) and TBA in TPA + EG + DOW group women were(30.68 +/- 8.58) U/L, (9.53 +/- 6.63) mumol/L respectively, significantly higher than those in TPA, DOW and control groups(P < 0.05, P < 0.01). Compared with TPA, DOW and control groups, the values of urine N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-2-microglobulim (beta 2-MG) in TPA + EG + DOW group of both men and women increased significantly(P < 0.05, P < 0.01), with(5.68 +/- 4.01) U/mmol Cr and (23.49 +/- 13.44) mg/mol Cr, and(6.68 +/- 4.68) U/mmol Cr and (22.80 +/- 13.00) mg/mol Cr, respectively. Analysis of regression indicated that both liver and renal injuries of the workers were evidently correlated with their exposure to TPA, EG and DOW after adjustment for the confounding factors such as sex, smoking, drinking, etc(P < 0.001). CONCLUSION: Based on available knowledge, it is reasonable to assume that the joint actions should be considered on the injury of liver and kidney caused by TPA, EG and(or) DOW among the workers. Serum ALT, GGT, TBA, urine NAG and beta 2-MG should be suggested as biomarkers for liver and kidney damage.

[Analysis on the components of rat urinary stone induced by terephthalic acid].

In order to analyze the components of rat urinary stone and to explore the possible mechanism of chemically induced bladder cancer, terephthalic acid (TPA) is orally administrated to rats at the doses of 5000 and 500 mg/kg/BW/everyday for consecutive 90 days and stones in bladder and kidney are collected. Inductive Coupled Plasma Quantomer (ICP), Element Analyzer (EA) and Fourier Transform Infared Spectrometer (FT-IR) are applied for the analysis on the components of stone in bladder and kidney. The results showed that the main components of the stone are calcium, carbon, nitrogen, hydrogen and phosphorus. The FT-IR showed that the stones both in bladder and kidney might contain nitrous, carbonate, ammonium salt, and para-position replaced benzene-ring compounds, but no original TPA is detected. The findings indicate that TPA might have a metabolic turnover inside the rat body, and, at least, might not be completely excreted in its original form.

[Study on the bladder calculi and bladder cancer induced by terephthalic acid in rats].

The carcinogenicity and calculogenesis of terephthalic acid on bladder was investigated. Terephthalic acid at doses of 5000, 500 and 50 mg/kg body weight/d were administrated to SD rats for 90 days consecutively. Control animals received normal feeds. Bladder calculi were induced in 5000 mg/kg (10/17) and 500 mg/kg (2/18) group. Calculi incidence of male rats was higher than that of female rats in 5000 mg/kg dose group. Bladder transitional cell cancer (4/17), atypical hyperplasia (5/17) and single hyperplasia (7/17) could be observed in 5000 mg/kg group. Atypical hyperplasia (10/18) and single hyperplasia (5/18) could be observed in 500 mg/kg group. Single hyperplasia (10/17) could be observed in 50 mg/kg group. The controls were normal except 1 case of single hyperplasia (1/18). There was a positive correlation between pathologic changes and dosage, but no significant correlation between pathologic changes and calculi incidence. Those rats without calculi produced some changes too, but no squamous metaplasia and carcinoma happened. The results suggested that under the study conditions, squamous cell carcinogenicity might be induced by terephthalic acid, and the calculi might not be the major factor inducing cancer.

[Study on the injury of liver induced by terephthalic acid ethylene glycol and/or dowtherm A in rats].

The joint injury actions and mechanisms of terephthalic acid (TPA), ethylene glycol (EG) and/or dowtherm A (DOW) on liver in rats were investigated. A subchronic toxicity study was designed by a 2(3) factorial method. Some enzymes, biochemical and morphologic indices reflecting the injury of liver were studied. The results showed that serum ALT and serum total bile acid (TBA) of rats in the combined intoxication groups were significantly higher than those in the groups with single toxic agent and control group. The results of factorial analysis showed that the joint action induced by TPA, EG and/or DOW were characterized as additive (TPA + EG), synergistic (EG + DOW), synergistic (TPA + DOW) and additive(TPA + EG + DOW) actions. The deduction was identified by morphologic observations.