A Mendelian randomization study on the causal relationship between smoking, alcohol consumption, and the development of myopia and astigmatism.

The influence of environmental factors like smoking and alcohol on myopia and astigmatism is controversial. However, due to ethical concerns, alternative study designs are urgently needed to assess causal inference, as mandatory exposure to cigarettes and alcohol is unethical. Following comprehensive screenings, 326 single nucleotide polymorphisms (SNPs) related to myopia and astigmatism were included in the dataset. To validate the causal association between exposures such as cigarette smoking, alcohol consumption, and coffee intake, and outcomes namely astigmatism and myopia, five regression models were employed. These models encompassed MR-Egger regression, random-effects inverse-variance weighted (IVW), weighted median estimator (WME), weighted model, and simple model. The instrumental variables utilized in these analyses were the aforementioned SNPs. Apply Cochran's Q test to determine heterogeneity of SNPs; if heterogeneity exists, focus on IVW model results. The IVW model showed a 1.379-fold increase in the risk of astigmatism (OR = 1.379, 95%CI 0.822~2.313, P = 0.224) and a 0.963-fold increase in the risk of myopia (OR = 0.963, 95%CI 0.666~1.393, P = 0.841) for each unit increase in smoking. For each unit increase in coffee intake, the risk of astigmatism increased 1.610-fold (OR = 1.610, 95%CI 0.444~5.835, P = 0.469) and the risk of myopia increased 0.788-fold (OR = 0.788, 95%CI 0.340~1.824, P = 0.578). For each additional unit of alcohol consumption, the risk of astigmatism increased by 0.763-fold (OR = 0.763, 95%CI 0.380~1.530, P = 0.446), and none of the differences were statistically significant. However, for each unit of alcohol consumption, the risk of myopia increased by 1.597 times, and the difference was statistically significant (OR = 1.597, 95%CI 1.023~2.493, P = 0.039). The findings indicate that alcohol consumption is a risk factor for myopia but smoking and coffee intake do not affect its development. Additionally, there is no association between smoking, alcohol consumption, coffee intake, and the risk of astigmatism.

Ketamine reverses the impaired fear memory extinction and accompanied depressive-like behaviors in adolescent mice.

Post-traumatic stress disorder (PTSD) is a chronic and disabling condition arising after exposure to a severe traumatic event, which affects approximately eight percent of the population. The underlying neurobiology of PTSD, however, has only been partially understood. The exploration of fear memory and its extinction has been the subject to increase our understanding of PTSD. Our previous studies have already found that adolescent mice exhibited impaired fear memory extinction with accompanied depressive-like behaviors. Considering the relationship between ketamine and its rapid antidepressant function, we hypothesis that ketamine can facilitate the fear memory extinction so as to exhibit an antidepressant effects. In this study, to evaluate our hypothesis, we intraperitoneal (i.p.) injection of ketamine in adolescent mice and found that ketamine exhibited a rapid antidepressant effect and facilitated the fear memory extinction. Moreover, ketamine can also reverse the accompanied depressive-like behaviors and restore long-term potentiation (LTP) induction in extinction process, which involved the presynaptic mechanism. Our results suggest that ketamine exhibited an antidepressant effect in FST and facilitated the fear memory extinction via presynaptic-mediated synaptic plasticity, which may provide new strategy for treatment of PTSD.

Properties of a Stable and Sustained-Release Formulation of Recombinant Human Parathyroid Hormone (rhPTH) with Chitosan and Silk Fibroin Microparticles.

BACKGROUND Parathyroid hormone (PTH) is required for the maintenance of normal bone physiology. This study describes the properties of a sustained-release formulation of recombinant human PTH (rhPTH) using chitosan and silk fibroin microparticles as carriers for drug delivery, developed using a spray-drying method. MATERIAL AND METHODS Chitosan, silk fibroin, and chitosan/silk fibroin microparticles loaded with rhPTH were studied with scanning electron microscopy (SEM) to estimate the particle size and surface morphology. The in vitro release of rhPTH was used to assess the developed formulation. The effect of the spray-drying process was assessed by powder X-ray diffraction (PXRD) of the microparticles. Quantification of the released rhPTH was performed by enzyme-linked immune sorbent assay (ELISA). Fourier-transform infrared spectroscopy (FTIR) was used to determine the differences in the absorption frequency of samples. RESULTS Surface morphology of the final formulation showed the absence of pure crystals of chitosan and silk fibroin in the final formulation and FTIR demonstrated electrostatic interactions between chitosan and silk fibroin, which was supported by PXRD. The chitosan/silk fibroin microparticles loaded with rhPTH showed an entrapment efficiency (EE) that ranged from 60.36-72.99% with a 50% rhPTH release profile at pH 7.5 in 24 hours. There was no particle aggregation in blood and little hemolysis, indicating stability of the rhPTH-loaded microparticles. CONCLUSIONS A silk fibroin/chitosan microparticle formulation loaded with rhPTH was shown to be stable and to provide sustained-release of rhPTH, supporting a potential role of this formulation in the treatment of bone diseases including osteoporosis and bone fracture.

Urinary S-phenylmercapturic acid as a key biomarker for measuring occupational exposure to low concentrations of benzene in Chinese workers: a pilot study.

OBJECTIVE: This study analyzed the level of urinary S-phenylmercapturic acid (U-SPMA) for low benzene exposure in a group of Chinese shoe-making workers. METHODS: Urinary samples from 55 workers exposed to benzene at levels lower than 10 parts per million (ppm) were collected at postshift. U-SPMA level was determined using high-performance liquid chromatography/mass spectrography (HPLC/MS) method. RESULTS: Good linearity of U-SPMA was observed within the range from 10 to 320 µg/L (r = 0.9994). Concentration of airborne benzene ranged from 0.71 to 32.17 mg/m³, and three segments were divided with different levels of exposure (≤6.0, 6.0 to 10.0, 10 to 32.5 mg/m³), the median U-SPMA concentrations were 49.55, 102.15, and 335.69 µg/g Cr, respectively. CONCLUSION: A good linear correlation was found between U-SPMA levels and airborne benzene concentrations. The selected method could be applied for detecting other working conditions in China.

[Inhibition of curcumin on histone deacetylase and expression promotion of P21 (WAF1/CIP1) in HepG2 cells].

OBJECTIVE: To investigate the effect of curcumin (Cur) on histone deacetylase (HDAC1) and P21(WAF1/CIP1), a cyclin dependent kinase inhibitor, in HepG2 cells for exploring the mechanism of Cur in anti-cancer. METHOD: The HDAC1, P21(WAF1/CIP1) proteins and P21(WAF1/CIP1) mRNA were extracted from human hepatoma cells treated with or without Cur of different concentrations at different time points. Western blot analysis was performed to determine the levels of HDAC1 and P21(WAF1/CIP1) proteins, respectively. RT-PCR was performed to detect the level of P21(WAF1/CIP1) mRNA. RESULT: The IC50 of concentration treated by Cur was 25 micromol x L(1) on HepG2 cell. The level of HDAC1 was obviously inhibited by Cur, and decreased at 4 hours at IC, and lasted for 48 h in a time-dependent manner. The inhibition of HDAC1 was significant at the Cur concentration of 12.5 micromol x L(-1) but there was no difference between 50 and 100 micromol x L(-1). The levels of P21(WAF1/CIP1) mRNA and protein were up-regulated by Cur in dose and time-dependent manner, and the change of mRNA and protein was detected at 8 hours and lasted for 48 hours. CONCLUSION: Cur can inhibit the level of HDAC1 and enhance the expression of P21(WAF1/CIP1) protein and mRNA, and the results suggest that inhibiting HDAC1 and increasing P21(WAF1/CIP1) may be one of the possible mechanisms of anti-cancer by Cur.