Clinical ocular surface characteristics and expression of MUC5AC in diabetics: a population-based study.

OBJECTIVES: To investigate the clinical characteristics and the expression of mucin 5AC (MUC5AC) in in diabetic and non-diabetic subjects with or without dry eye disease. METHODS: A total of 399 participants (796 eyes) aged 50-80 years were enrolled in this study. Participants were divided into 4 groups: non-diabetic without dry eye group (normal group), non-diabetic with dry eye group, diabetic without dry eye group and diabetic with dry eye group. Demographic information, fasting plasma glucose (FBG), and glycated haemoglobin A1C (HbA1C) data were collected. Additionally, ocular surface disease index (OSDI) questionnaire, signs of dry eye, tear osmolarity, and meibomian glands were evaluated. Tear MUC5AC expression and conjunctival goblet cells density (GCD) were tested. RESULTS: Compared with non-diabetic with dry eye group, diabetic with dry eye group showed significantly lower tear film osmolarity (TFO), but higher corneal fluorescein and conjunctival lissamine green staining scores. In comparison with diabetic without dry eye group, diabetic with dry eye group showed significantly higher TFO, corneal fluorescein and conjunctival lissamine green staining scorers. The MUC5AC concentration and GCD of diabetic with dry eye group was significantly lower than those of the non-diabetic with dry eye group. Diabetic subjects with higher HbA1c levels (≥7.8%) showed higher TFO and shorter fluorescein tear break time. CONCLUSION: Diabetics with dry eye exhibited notably higher corneal fluorescein and conjunctival lissamine green staining scores. Conjunctival goblet cells and MUC5AC were significantly reduced in diabetics. Higher TFO was associated with the duration of diabetes and HbA1c levels.

Identification of key genes modules linking diabetic retinopathy and circadian rhythm.

Background: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Recent studies highlighted the crucial impact of circadian rhythms (CR) on normal retinopathy in response to the external light cues. However, the role of circadian rhythms in DR pathogenesis and potential investigational drugs remains unclear. Methods: To investigate the weather CR affects DR, differential expression analysis was employed to identify differentially expressed genes (DEGs) from the GEO database (GSE160306). Functional enrichment analysis was conducted to identify relevant signaling pathways. LASSO regression was utilized to screen pivotal genes. Weighted gene co-expression network anlaysis (WGCNA) was applied to identify different modules. Additionally, we use the Comparative Toxicogenomics Database (CTD) database to search key genes related to drugs or molecular compounds. The diabetic mouse model received three consecutive intraperitoneal injections of streptozotocin (STZ) during 3 successive days. Results: We initially identified six key genes associated with circadian rhythm in DR, including COL6A3, IGFBP2, IGHG4, KLHDC7A, RPL26P30, and MYL6P4. Compared to normal tissue, the expression levels of COL6A3 and IGFB2 were significantly increased in DR model. Furthermore, we identified several signaling pathways, including death domain binding, insulin-like growth factor I binding, and proteasome binding. We also observed that COL6A3 was positively correlated with macrophages (cor=0.628296895, p=9.96E-08) and Th17 cells (cor=0.665120835, p=9.14E-09), while IGFBP2 showed a negatively correlated with Tgd (cor=-0.459953045, p=0.000247284) and Th2 cells (cor=-0.442269719, p=0.000452875). Finally, we identified four drugs associated with key genes: Resveratrol, Vitamin E, Streptozocin, and Sulindac. Conclusion: Our findings revealed several key genes related to circadian rhythms and several relevant drugs in DR, providing a novel insight into the mechanism of DR and potential implications for future DR treatment. This study contributes to a better understanding of CR in DR and its implications for future therapeutic interventions.

A combination of CMC and α-MSH inhibited ROS activated NLRP3 inflammasome in hyperosmolarity stressed HCECs and scopolamine-induced dry eye rats.

An important mechanism involved in dry eye (DE) is the association between tear hyperosmolarity and inflammation severity. Inflammation in DE might be mediated by the NLRP3 inflammasome, which activated by exposure to reactive oxygen species (ROS). A combination of carboxymethylcellulose (CMC) and α-melanocyte stimulating hormone (α-MSH) may influence DE through this mechanism, thus avoiding defects of signal drug. In this study, we assessed whether treatment comprising CMC combined with α-MSH could ameliorate ocular surface function; we found that it promoted tear secretion, reduced the density of fluorescein sodium staining, enhanced the number of conjunctival goblet cells, and reduced the number of corneal apoptotic cells. Investigation of the underlying mechanism suggested that the synergistic effect of combined treatment alleviated DE inflammation through reduction of ROS level and inhibition of the NLRP3 inflammasome in human corneal epithelial cells. These findings indicate that combined CMC + α-MSH treatment could ameliorate lesions and restore ocular surface function in patients with DE through reduction of ROS level and inhibition of NLRP3 signalling.

[Detection Method, Distribution, and Risk Assessment of Pharmaceuticals and Personal Care Products in the Yellow Sea and the East China Sea].

At present, research findings on pharmaceuticals and personal care products (PPCPs) in coastal areas are still unclear, and there is a need to develop a method to detect more PPCPs simultaneously in seawater. In this study, nine compounds of non-steroidal anti-inflammatory drugs, antibiotics, lipid regulators. and stimulants were selected as analytes. Solid phase extraction (SPE) was used to extract the compounds, which were then analyzed by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The optimum experimental conditions, such as the filler, eluent, pH, flow rate, and the reduction of matrix effect were optimized during the SPE. The results showed that the best extraction column was CNW HLB, the best eluent was methanol:acetonitrile (1:1, volume ratio), the best eluent volume was 6 mL, the best pH was 7, the best flow rate was 5 mL·min-1, the amount of EDTA-Na2 added was 1 g, and the best concentration multiple was 500. The linear regression equations of all PPCPs had good linearity. Correlation coefficients were>0.999, recovery rates were between 82%-106%, relative standard deviations were between 1.6%-14%, and detection limits were between 0.01-2 ng·L-1, thus satisfying the requirement of trace analysis in seawater. Distribution characteristics and sources of PPCPs were studied in the Yellow Sea and the East China Sea during summer 2018. All nine PPCPs were detected and the main pollutants were NAP, IBU, GEM, CAF, and ASA. High concentrations of PPCPs were generally detected in the nearshore area and displayed conspicuous decreasing tendencies from the inshore towards the offshore. The concentrations of PPCPs in the Yellow Sea were higher than of those in the East China Sea, and this was related to there being more sources of pollutions and poor water exchange capacity in the Yellow Sea. Principal component analysis showed that the main source of PPCPs was terrestrial input. The environmental risk assessment of PPCPs indicated that risk quotients (RQs) of IBU and NAP (0.1-1) posed a medium risk to the aquatic environment, while others posed low risk to organisms.

[Effect and Approach of Enteromorpha prolifera Biochar to Improve Coastal Saline Soil].

The use of biochar to improve adversity of soil has received increasing attention. Enteromorpha prolifera biochar is used to repair coastal saline-alkali soil, which can not only utilize Enteromorpha prolifera but can also increase the scale of the coastal land reserve. In this study, the method of soil culture experiments was used to explore the effect and pathway of 0%-3% addition of Enteromorpha prolifera on the improvement of saline-alkali soil. The results showed that the optimum preparation temperature of Enteromorpha prolifera biochar suitable for saline-alkali soil improvement was 400℃, and the optimum addition amount was 1.5%. At the optimum level, although the biochar had a negative effect, such as increasing soil salinity (0.12%) and pH (1.49%), it also produced positive effects, such as reducing soil Na+/K+ by 55.73%, increasing mineral content, and improving water conductivity. Enteromorpha prolifera biochar improved soil physicochemical and biological properties, increased nutrient content, enhanced microbial activity, improved soil nutrient availability, and produced positive effects. These positive effects were characterized by reducing soil bulk density by 11.35%, increasing organic matter by 42.64%, increasing the proportion of organic carbon in total carbon by 3.84 times, increasing the proportion of available phosphorus in total phosphorus by 4.15 times, and increasing soil invertase activity by 2.39 times, urease activity by 1.18 times, and catalase activity 1.50 times. Therefore, the positive effect of Enteromorpha prolifera biochar on saline-alkali soil is more than negative, and it can be used for the improvement of coastal saline-alkali soil. This study provides a new path for the resource utilization of Enteromorpha prolifera and the improvement of the ecological environment of coastal saline-alkali soil.

Carboxymethyl Cellulose-Coated Tacrolimus Nonspherical Microcrystals for Improved Therapeutic Efficacy of Dry Eye.

Dry eye (DE) is a highly prevalent ocular surface disease which affects the quality of life and results in low working efficiency. Frequent instillation is required due to low bioavailability of conventional eye drops. The aim of this study is to develop a novel formulation of tacrolimus (TAC), routinely prescribed for DE, by combination of the microcrystal technology and layer-by-layer assembly. First, nonspherical tacrolimus microcrystals (TAC MCs) are synthesized by antisolvent-induced precipitation. These TAC MCs are modified by alternate deposition of poly(allylamine hydrochloride) (PAH) and carboxymethyl cellulose (CMC) subsequently to obtain CMC-coated TAC MCs (TAC-(PAH/CMC)3 ). The resultant formulations are evaluated in vivo in a mouse DE model induced by an intelligently controlled environmental system. Compared with commercially available TAC eye drops and the TAC MCs counterpart, TAC-(PAH/CMC)3 exhibits superior therapeutic performance with reduced drug instillation frequency, which is attributed to the nonspherical geometry of MCs, the lubricant, mucoadhesive effect of CMC, and the anti-inflammatory function of TAC. Therefore, TAC-(PAH/CMC)3 represents a better option for the management of DE.