To study the potential relationship between melatonin and beta-amyloid (Abeta), we established a liquid chromatography-mass spectrometry (LC-MS) method to quantitatively analyze melatonin, deuterated isotopes (melatonin-D4), and internal standard 6-iodo-2-(4'-dimethylamino-) phenyl-imidazo(1,2) pyridine (IMPY) under positive (+) mode. The gradient elution was set to 6 min, and the corresponding peak time of melatonin and its isotope melatonin-D4 was 3.14 min, while the peak time for the internal standard IMPY was 3.24 min. Next, we established and optimized the molecule receptor saturation binding assay based on LC-MS to determine the melatonin affinity for beta-amyloid (Abeta). Melatonin showed a high and specific binding for Abeta. The corresponding equilibrium dissociation constant (Kd) of melatonin with Abeta 1-40 and Abeta 1-42 was 814.37 AE 36.62 and 628.33 AE 13.57 nmolÁL À1 ; besides, the Kd of melatonin with mixed plaques (1-40 and 1-42) was 461.13 AE 45.37 nmolÁL À1 . The results may suggest the potential mechanism of action of MT on Abeta and provide a theoretical basis for the improvement of MT treatment of Alzheimer's disease.
Background Human papillomavirus (HPV) infection rates in women vary regionally. This study analyzed HPV infection in women of different age groups in Hefei, China, performed follow-up on positive cases, and discussed infection prognoses. Methods Samples (7,222) of exfoliated cervical cells were collected in Hefei and tested with an HPV assay kit against 27 HPV genotypes. Statistical software was used to analyze the data. Results The total positive rate of infection was 17.13% (1,068 women), and the 51–60-year age group had the highest HPV infection rate (19.82%). There were statistically significant differences between rates in the 21–30 and 31–40 (P = 0.002), 21–30 and 41–50 (P = 0.0003), 21–30 and 51–60 (P = 0.00003), and 51–60 and >60 age groups (P = 0.046). High-risk infection (15.67%) and single infection (13.01%) were the main types of HPV infection. The dominant genotypes of high-risk infection were HPV 52 (2.42%), HPV 16 (2.01%), HPV 53 (1.43%), HPV 58 (1.32%) and HPV 66 (1.01%). We conducted follow-up on cases in 69 of 94 women who had a history of 1–4 years of positive infection, and in 18 (seven treated, 11 untreated) patients, infection status turned negative (26.09%). Seventeen of the fifty-one women whose infections did not turn negative received treatment. Persistent infection was predominantly observed in high-risk genotypes (56 of 69). Conclusions The results recommend that women in Hefei improve health awareness and receive a 9-valent vaccine. Additionally, women with persistent infections should consult a gynecologist to prevent cervical lesions.
Background: Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people. Objectives: By designing and synthesizing intracerebral imaging probes, we try to provide a new solution for early diagnosis of AD. Methods: We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments. Results: In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, Kd values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The LogP value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared with the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD50 was > 100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120 min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection. Conclusion: All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.
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