Research progress on animal models of corneal epithelial-stromal injury.

A corneal epithelial-stromal defect is recognized as a major contributor to corneal scarring. Given the rising prevalence of blindness caused by corneal scarring, increasing attention has been focused on corneal epithelial-stromal defects. Currently, the etiology and pathogenesis of these defects remain inadequately understood, necessitating further investigation through experimental research. Various modeling methods exist both domestically and internationally, each with distinct adaptive conditions, advantages, and disadvantages. This review primarily aims to summarize the techniques used to establish optimal animal models of corneal epithelial-stromal injury, including mechanical modeling, chemical alkali burns, post-refractive surgery infections, and genetic engineering. The intention is to provide valuable insights for studying the mechanisms underlying corneal epithelial-stromal injury and the development of corresponding therapeutic interventions.

Long-read assembled metagenomic approaches improve our understanding on metabolic potentials of microbial community in mangrove sediments.

BACKGROUND: Mangrove wetlands are coastal ecosystems with important ecological features and provide habitats for diverse microorganisms with key roles in nutrient and biogeochemical cycling. However, the overall metabolic potentials and ecological roles of microbial community in mangrove sediment are remained unanswered. In current study, the microbial and metabolic profiles of prokaryotic and fungal communities in mangrove sediments were investigated using metagenomic analysis based on PacBio single-molecule real time (SMRT) and Illumina sequencing techniques. RESULTS: Comparing to Illumina short reads, the incorporation of PacBio long reads significantly contributed to more contiguous assemblies, yielded more than doubled high-quality metagenome-assembled genomes (MAGs), and improved the novelty of the MAGs. Further metabolic reconstruction for recovered MAGs showed that prokaryotes potentially played an essential role in carbon cycling in mangrove sediment, displaying versatile metabolic potential for degrading organic carbons, fermentation, autotrophy, and carbon fixation. Mangrove fungi also functioned as a player in carbon cycling, potentially involved in the degradation of various carbohydrate and peptide substrates. Notably, a new candidate bacterial phylum named as Candidatus Cosmopoliota with a ubiquitous distribution is proposed. Genomic analysis revealed that this new phylum is capable of utilizing various types of organic substrates, anaerobic fermentation, and carbon fixation with the Wood-Ljungdahl (WL) pathway and the reverse tricarboxylic acid (rTCA) cycle. CONCLUSIONS: The study not only highlights the advantages of HiSeq-PacBio Hybrid assembly for a more complete profiling of environmental microbiomes but also expands our understanding of the microbial diversity and potential roles of distinct microbial groups in biogeochemical cycling in mangrove sediment. Video Abstract.

Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?

AIM: To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and if liver B-ultrasound can be used for its diagnosis. METHODS: We classified 861 obese children (6-16 years old) into three subgroups: group 0 (normal liver in ultrasound and normal transaminases); group 1 (fatty liver in ultrasound and normal transaminases); and group 2 (fatty liver in ultrasound and elevated transaminases). We measured the body mass index, waist and hip circumference, blood pressure, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), lipid profile and transaminases in all the participants. The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination. RESULTS: Among the 861 obese children, 587 (68.18%) were classified as having NAFLD, and 221 (25.67%) as having MS. The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587), which was much higher than that in non-NAFLD group (group 0, 12.04%) (P < 0.01). There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05). The incidence of NAFLD in MS patients was 84.61% (187/221), which was significantly higher than that of hypertension (57.46%, 127/221) and glucose metabolic anomalies (22.62%, 50/221), and almost equal to the prevalence of dyslipidemia (89.14%, 197/221). Based on the B-ultrasound scales, the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR): 2.18, 95% confidence interval (95% CI): 1.27-3.75], dyslipidemia (OR: 7.99, 95% CI: 4.34-14.73), impaired fasting glucose (OR: 3.65, 95% CI: 1.04-12.85), and whole MS (OR: 3.77; 95% CI: 1.90-7.47, P < 0.01). The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased. CONCLUSION: NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and liver B-ultrasound can be a useful tool for MS screening.

[Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes].

OBJECTIVE: To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet. METHOD: Male SD rats (n = 36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group I: ordinary diet, group II: high-fat diet, group III: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2 (sPLA2), lysophosphatidylcholine (LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). In addition, the histological changes of liver tissue were analyzed. RESULT: Compared to ordinary diet group, the rat's liver weight (g) (16.92 ± 2.49 vs. 12.16 ± 0.82), hepatic exponent (0.034 ± 0.004 vs. 0.026 ± 0.002), serum alanine aminotransferase (U/L) (45.43 ± 9.73 vs. 29.42 ± 6.73), triglyceride (mmol/L) (1.22 ± 0.24 vs. 0.85 ± 0.19), cholesterol (mmol/L) (2.00 ± 0.37 vs. 1.49 ± 0.33), lipoprotein(a) (mmol/L) (743.86 ± 32.19 vs. 648.42 ± 78.87), low-density lipoprotein (mmol/L) (1.31 ± 0.35 vs. 0.65 ± 0.22), insulin (mmol/L) (22.16 ± 5.16 vs. 16.86 ± 5.35), insulin resistance index(5.10 ± 1.45 vs. 3.59 ± 0.99), free fatty acid (mEq/L) (0.57 ± 0.10 vs. 0.35 ± 0.07), sPLA2 [µmol/(min·ml)] (0.130 ± 0.016 vs. 0.098 ± 0.024), lysophosphatidylcholine (µmol/L) (707.26 ± 92.48 vs. 508.87 ± 96.50), leptin (pg/ml (80.08 ± 17.73 vs. 65.11 ± 14.09), liver triglyceride (mg/g) (13.57 ± 0.65 vs. 12.03 ± 1.14), cholesterol (mg/g) (2.19 ± 0.15 vs. 1.94 ± 0.12) (P < 0.05) were significantly increased in high-fat diet group. Moreover, degree of hepatic steatosis was significantly higher and sPLA2 mRNA expression was also significantly increased. Secondly, in comparison with high-fat diet group, early metformin treatment significantly reduced the rat's body weight (g) (394.40 ± 33.10 vs. 491.86 ± 26.45), liver weight (g) (13.24 ± 1.16 vs. 16.92 ± 2.49), serum alanine aminotransferase (U/L) (30.40 ± 4.50 vs. 45.43 ± 9.73), triglyceride (mmol/L) (0.75 ± 0.19 vs. 1.22 ± 0.24), cholesterol (mmol/L) (1.61 ± 0.38 vs. 2.00 ± 0.37), insulin (mmol/L) (16.96 ± 5.60 vs. 22.16 ± 5.16), insulin resistance index (3.75 ± 1.41 vs. 5.10 ± 1.45), sPLA2 [µmol/(min·ml)] (0.101 ± 0.009 vs. 0.130 ± 0.016), lysophosphatidylcholine (µmol/L) (549.92 ± 90.78 vs. 707.26 ± 92.48), liver triglyceride (mg/g) (11.23 ± 1.70 vs. 13.57 ± 0.65), cholesterol (mg/g) (1.97 ± 0.20 vs. 2.19 ± 0.15) (P < 0.05). Moreover, degree of hepatic steatosis was significantly lower and sPLA2 mRNA expression was also significantly decreased by metformin. Thirdly, when compared to ordinary diet group, metformin could also significantly increase hepatic exponent (0.034 ± 0.004 vs. 0.026 ± 0.002) and low-density lipoprotein level (mmol/L) (0.96 ± 0.34 vs. 0.65 ± 0.22) (P < 0.05). However, it had no impact on hepatic steatosis and sPLA2 expression (P > 0.05). CONCLUSION: It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function.

[Relationship between nonalcoholic fatty liver disease and cardiovascular disease in children with obesity].

OBJECTIVE: To study the relationship between nonalcoholic fatty liver disease (NAFLD) and the development of cardiovascular disease (CVD) in children with obesity. METHODS: Two hundred and thirty-one obese children and 24 non-obese children as control were enrolled. Body mass index (BMI), serum triglyceride, blood pressure, liver function, and carotid artery intima-media thickness (IMT) were examined. The obese children were classified into two subgroups according to the diagnosis criteria: group 1 without liver disorder (OCWLD group, n=75) and group 2 with NAFLD (NAFLD group, n=156). The incidences of hyperlipidemia and hypertension, carotid artery intima-media thickness (IMT) and biochemical indicators were compared in the three groups. RESULTS: The NAFLD group showed significantly greater carotid IMT (0.066+/-0.021 cm) than the OCWLD (0.060+/-0.011 cm) and control groups (0.037+/-0.007 cm) (P<0.05). The OCWLD group had also thicker IMT than the control group (P<0.05). The incidences of hyperlipidemia and hypertension were 39.7% and 40.4%, respectively in the NAFLD group, which were significantly higher than those in the OCWLD (22.7% and 29.3% respectively)and control groups (4.2% and 12.6% respectively) (P<0.05). The liner stepwise regression analysis showed that the IMT was positively correlated with BMI, NAFLD and ALT (adjusted R2=0.316, P<0.01). CONCLUSIONS: NAFLD may be not only an early marker but also an early state of CVD in obese children. Early diagnosis and treatment of NAFLD is crucial for the prevention of the occurrence and development of CVD.