Quantum chemistry calculation-aided discovery of potent small-molecule mimics of glutathione peroxidases for the treatment of cisplatin-induced hearing loss.

Hearing loss (HL) is a health burden that seriously affects the quality of life of cancer patients receiving platinum-based chemotherapy, and few FDA-approved treatment specifically targets this condition. The main mechanisms that contribute to cisplatin-induced hearing loss are oxidative stress and subsequent cell death, including ferroptosis revealed by us as a new mechanism recently. In this study, we employed the frontier molecular orbital (FMO) theory approach as a convenient prediction method for the glutathione peroxidase (GPx)-like activity of isoselenazolones and discovered new isoselenazolones with great GPx-like activity. Notably, compound 19 exhibited significant protective effects against cisplatin-induced hair cell (HC) damage in vitro and in vivo and effectively reverses cisplatin-induced hearing loss through oral administration. Further investigations revealed that this compound effectively alleviated hair cell oxidative stress, apoptosis and ferroptosis. This research highlights the potential of GPx mimics as a therapeutic strategy against cisplatin-induced hearing loss. The application of quantum chemistry (QC) calculations in the study of GPx mimics sheds light on the development of new, innovative treatments for hearing loss.

Association between red blood cell distribution width-to-albumin ratio and diabetic retinopathy.

BACKGROUND: Diabetes mellitus (DM) has shown a trend of reaching pandemic levels in the world. Chronic inflammation is a key factor in the development of diabetic retinopathy (DR). Red blood cell distribution width-to-albumin ratio (RA) is used to assess immune status and the immune response. Our study was conducted to assess the association between DR and RA levels to determine the value of RA in predicting DR. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2006, The RA was calculated as the Red Blood Cell Distribution Width/Albumin Ratio. Multivariable logistic regression and propensity score-matched analysis were used to examine the association between RA and DR levels. RESULTS: The clinical and demographic features of the 1,751 patients with DM. The eligible participants included 874 females and 870 males with mean age 62.2 ± 14.0 years, and mean RA 3.2 ± 0.5. RA ≥ 2.9659 was a risk factor for DR (OR = 1.66 95% CI: 1.31-2.11, p < 0.0001). After adjusting for age, sex, race, education, marital status, ratio of family income to poverty, body mass index, fasting glucose, hypertension, and coronary heart disease, RA ≥ 2.9659 was an independent risk factor for DR (OR = 1.64, 95% CI: 1.23-2.19, p = 0.0008). The propensity score-matched analysis also showed that high RA was an independent risk factor for DR. CONCLUSIONS: Our study shows that RA is a risk factor for patients with DR. The findings of this study should be validated the role of RA in DR in diabetic patients.

Allisartan ameliorates vascular remodeling through regulation of voltage-gated potassium channels in hypertensive rats.

BACKGROUND: The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats. METHODS: The study included a total of 47 Sprague Dawley (SD) rats. The animals were randomized to sham operation (n = 14), untreated hypertensive control group (n = 18) and allisartan treatment group (n = 15). Using renal artery stenosis, hypertension was induced in animals. Single dose of allisartan was administered intra-gastrically to animals in the allisartan treatment group and match placebo in the other 2 groups. Wire myography was used to measure the muscle tension in isolated mesenteric arteries from the animals. Real-time polymerase chain reaction was used to quantify the expression of Kv7 channel mRNA subunits. RESULTS: After 4 weeks of treatment, a significant decrease in mean arterial, systolic and diastolic blood pressure (SBP and DBP) was observed in allisartan treatment group compared to hypertension control group. The median arterial wall thickness and area/diameter ratio reduced significantly in treatment group compared to untreated hypertension group (P < 0.05). Wire myography demonstrated increased relaxation of mesenteric artery with increase in concentration of ML213. A significant up-regulation in the expression of all Kv7 mRNA subunits was observed in allisartan group compared to untreated hypertension group. CONCLUSIONS: From the results, allisartan was found to lower BP and preserve vascular remodeling through Kv7 channels.

Optical Coherence Tomography Angiography in Pinguecula and Pterygium.

PURPOSE: To investigate the density of conjunctival blood vessels in normal eyes and in eyes with pinguecula or pterygium. METHODS: In this cross-sectional study, the conjunctival blood vessel density of 15 normal eyes, 15 pinguecula eyes, and 15 pterygium eyes of 43 healthy adults was assessed using optical coherence tomography angiography with an anterior segment lens adapter. The nasal surface of each eye (3 × 3 mm) was scanned 3 times to a depth of 800 µm. Conjunctival vessel density was defined as the percent of the scanned volume occupied by vessels in which blood flow was measured. RESULTS: The high reliability of data measurement was supported by good coefficients of repeatability (<10%) of the image quality score and high intraclass correlation coefficients (>0.9). The vessel density in normal conjunctivas, 52.2 ± 4.1%, was similar to that in pinguecula conjunctivas, 50.5 ± 4.7% (P = 0.3006). However, the vessel density in conjunctivas with pterygium, 63.6 ± 3.7%, was greater than that in either normal (P < 0.0001) or pinguecula (P < 0.0001) conjunctivas. CONCLUSIONS: Using optical coherence tomography angiography with an anterior segment lens adapter, the ocular surface blood vessel density was imaged and assessed with good repeatability and reliability. The blood vessel density of conjunctivas with pterygium was significantly greater than that in either normal or pinguecula conjunctivas. This suggests that, in contrast to pinguecula development, pterygium development includes angiogenesis and neovascularization.

Repeatability of ocular surface vessel density measurements with optical coherence tomography angiography.

BACKGROUND: To determine the repeatability of measurements of ocular surface vessel density in normal and diseased eyes using optical coherence tomography angiography (OCTA). METHODS: Ten normal eyes, 10 pinguecula eyes, and 10 pterygium eyes of 30 volunteers were subjected to OCTA (AngioVue Imaging System, Optovue, Inc.). For scanning, we used the corneal adapter module. Each eye was scanned three times in the nasal and temporal directions, separately. AngioVue software was used to generate the ocular surface vessel density. Ocular surface vessel density was defined as the proportion of vessel area with blood flow to the total measurement area (3 × 3 mm2). Intersession repeatability of the measurement was summarized as the coefficient of variation (CV), and intraclass correlation coefficients (ICC) were calculated by variance component models. RESULTS: The CVs were less than 5% in all subjects, and the ICCs exceeded 0.9; thus, all measurements showed good repeatability. The nasal vessels densities differed significantly between healthy eyes and eyes with pterygium (P < 0.05); however, there was no significant difference between healthy eyes and eyes with pinguecula (P = 0.466). CONCLUSIONS: These results suggest that measurement of ocular surface vessel density by OCTA in normal eyes and eyes with pterygium and pinguecula is repeatable. This preliminary research describes a quantitative and visual method for assessing vessel density of the ocular surface with a high level of consistency.

[The germinating characters of the transgenic rice seeds in the stress condition of antibiotic G418 and their application in crop breeding].

The seeds of transgenic rice line D2-1-2 and the receptor cultivar Zhonghua No.9 were germinated on the stress condition of the antibiotic G418. The number of taking root seed, the length of root and the length of shoot of two used materials were checked in different concentrations of the antibiotic G418, but the ratio of germinating seed was not affected. At the 100 mg/L level of G418, the transgenic line D2-1-2 could take longer root (mean 1.45 cm) but Zhonghua No.9 very short (mean 0.27 cm). 88.46% of the total long-root (<0.5 cm) seeds selected from the mixing population of D2-1-2 and Zhonghua No.9 at the 100 mg/L level of antibiotic G418 were real transgenic ones.