Identification of novel therapeutic targets for Fuchs' endothelial corneal dystrophy based on gene bioinformatics analysis.

Fuchs' endothelial corneal dystrophy (FECD) is a disease where progressive visual impairment occurs by the thickening of the Descemet's membrane and the gradual degeneration and loss of corneal endothelial cells. This study aimed to investigate the key changes in gene expression associated with FECD and explore potential biomarkers and new therapeutic strategies for FECD. To explore the potential therapeutic targets of FECD, we downloaded the gene expression dataset GSE171830 from the Gene Expression Omnibus (GEO) database. A total of 303 differentially expressed genes (DEGs) were identified by the limma package. The enriched Gene Ontology (GO) annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs mostly included the extracellular matrix organization, collagen-containing extracellular matrix, and the structural constituents of the extracellular matrix. Fifteen hub genes from the most significant module were ascertained by Cytoscape. Both collagen-containing extracellular matrix and extracellular matrix hit to ANXA1, VCAN, GPC3, TNC, IGFBP7, MATN3, and SPARCL1 genes in the GO cellular components. Among these genes, the expression of SPARCL1 was down-regulated in the FECD samples, whereas the expression of GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 was up-regulated in the FECD samples. Gene set enrichment analysis (GSEA) plots showed that among the 20,937 genes, SPARCL1 played an important role in three pathways, cytokine-cytokine receptor interaction, the TGF-beta signaling pathway, and antigen processing and presentation. The top three pathways enriched by the GPC3, MATN3, IGFBP7, TNC, VCAN, and ANXA1 genes were those for cytokine-cytokine receptor interaction, TGF-beta signaling, and RIG-I-like receptor signaling. In conclusion, the DEGs identified here might assist clinicians in understanding the pathogenesis of FECD. Furthermore, these identified biomarkers might serve as potential therapeutic targets for the treatment of FECD.

In vivo and in vitro metabolism study of traditional Chinese medicine formula Dingkun Dan in rats by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study.

Efficacy of intense pulsed light and meibomian gland expression treatments in meibomian gland dysfunction: A meta-analysis of randomized controlled trials.

PURPOSE: This review aimed to evaluate the efficacy and safety of intense pulsed light treatment combined with meibomian gland expression treatments in meibomian gland dysfunction. METHODS: We conducted a meta-analysis of randomized controlled trials that compared the efficacy of intense pulsed light treatment and meibomian gland expression treatments in the treatment of dry eye disease. The meibomian gland yielding secretion score was the primary outcome, whereas the secondary outcomes included the Meiboscore, tear breakup time in seconds, standard patient evaluation for eye dryness and corneal fluorescein staining. RESULTS: This study consisted of 6 trials with 326 patients. Significantly greater improvement was observed in meibomian gland yielding secretion score at 1 month [mean difference (MD): 13.69 (95% CI, 11.98, 15.40)] and at 3 months [MD: 11.03 (95% confidence interval (CI), 10.27, 11.80)], low meibomian gland yielding secretion score at 1 month [MD: 6.92 (95% CI, 5.49, 8.34)] and at 3 months [MD: 6.80 (95% CI, 5.01, 8.59)], up meibomian gland yielding secretion score at 1 month [MD: 6.41 (95% CI, 4.12, 8.70)] and at 3 months [MD: 8.06 (95% CI, 5.70, 10.42)] and tear breakup time at 1 month [MD: 2.38 (95% CI, 1.83, 2.92)] and at 3 months [MD: 1.82 (95% CI, 1.48, 2.19)] in the IPL-MGX group than in the MGX group. CONCLUSIONS: IPL-MGX is safer and more efficacious as compared to the MGX alone in the treatment of patients with meibomian gland dysfunction-related dry eye. We recommend discussing the decision with the ophthalmologist for an appropriate choice.

Efficacy, Safety, and Tolerability of a Novel Cyclosporine, a Formulation for Dry Eye Disease: A Multicenter Phase II Clinical Study.

PURPOSE: The purpose of this study was to explore the efficacy, safety, and tolerability of a novel cyclosporine formulation for dry eye disease (DED). METHODS: This is an exploratory, multicenter, single-blind, randomized, positive-controlled Phase II clinical trial between cyclosporine ophthalmic gel (CyclAGel) and an open-label comparator (Restasis, positive control). A total of 240 eligible patients with moderate to severe DED were randomized to 4 study groups: CyclAGel 0.05%/once daily (QD) (n = 59), CyclAGel 0.05%/BID (n = 60), CyclAGel 0.1%/QD (n = 60), and Restasis 0.05%/BID (n = 61). After receiving BID dosing of hypromellose eye drops during a 2-week run-in period, patients were randomized to the respective treatment group and dosed QD or BID for 12 weeks. Efficacy was assessed based on a number of sign and symptom end points, including eye dryness score (visual analog scale), 6 other parameters of symptoms for dryness (burning/stinging, itching, foreign body sensation, discomfort, sensitivity to light, and pain), and corneal fluorescein staining. The Schirmer test was used to assess dry eye symptoms (visual analog scale severity) at visit 3 (week 2), visit 4 (week 6), and visit 5 (week 12). FINDINGS: CyclAGel showed a consistent improvement in eye dryness score and the 6 other parameters of symptoms for dryness, corneal fluorescein staining, breakup time, and Schirmer test scores compared with Restasis over the 12-week treatment period. However, there were no statistically significant differences between CyclAGel and Restasis after baseline corrections were made, and the results of the full analysis set remained consistent with those of the per-protocol set (P > 0.05). Moreover, each CyclAGel-treated group (0.05%/QD, 0.05%/BID, and 0.1%/QD) exerted better effects than the Restasis group, and CyclAGel 0.05%/QD showed the most significant improvement. The number of ocular-related treatment-emergent adverse events was low in all treatment groups, with no serious drug-related treatment-emergent adverse events. IMPLICATIONS: CyclAGel showed excellent safety, tolerability, and comfort profiles at 2 concentrations and frequency in moderate to severe DED.

Identification of pathogenic genes of pterygium based on the Gene Expression Omnibus database.

AIM: To identify the pathogenic genes in pterygium. METHODS: We obtained mRNA expression profiles from the Gene Expression Omnibus database (GEO) to identify differentially expressed genes (DEGs) between pterygium tissues and normal conjunctiva tissues. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein-protein interaction (PPI) network and transcription factors (TFs)-target gene regulatory network was performed to understand the function of DEGs. The expression of selected DEGs were validated by the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 557 DEGs were identified between pterygium and normal individual. In PPI network, several genes were with high degrees such as FN1, KPNB1, DDB1, NF2 and BUB3. SSH1, PRSS23, LRP5L, MEOX1, RBM14, ABCA1, JOSD1, KRT6A and UPK1B were the most downstream genes regulated by TFs. qRT-PCR results showed that FN1, PRSS23, ABCA1, KRT6A, ECT2 and SPARC were significantly up-regulated in pterygium and MEOX1 and MMP3 were also up-regulated with no significance, which was consistent with the our integrated analysis. CONCLUSION: The deregulated genes might be involved in the pathology of pterygium and could be used as treatment targets for pterygium.

Paraburkholderia caffeinitolerans sp. nov., a caffeine degrading species isolated from a tea plantation soil sample.

A Gram-stain negative, facultatively anaerobic, non-sporulating, non-motile and rod-shaped bacterium, designated CF3T, was isolated from a tea plantation soil sample and its taxonomic position was determined using polyphasic taxonomy. Strain CF3T displayed optimum growth at 25 °C, pH 5.0 and in the presence of 0-1 % NaCl. Comparative phylogenetic analysis of the 16S rRNA, recA and gyrB gene sequences showed that the isolate belongs to the genus Paraburkholderia, showing high levels of similarity with respect to Paraburkholderia oxyphila OX-01T (98.3, 95 and 93 %, respectively) and Paraburkholderia sacchari IPT101T (98.2, 95 and 95 %, respectively). The predominant ubiquinone was determined to be Q-8, and the polar lipids are phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified amino-phospholipid, three unidentified amino-lipids and three unidentified polar lipids. The major fatty acids were found to be C16:0, C17:0 cyclo, summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The DNA G+C content was found to be 63.8 mol% and the DNA-DNA relatedness values between strain CF3T and its two close relatives P. oxyphila OX-01T and P. sacchari IPT101T was 41 and 40 %, respectively. Based on phylogenetic analysis, phenotypic and genotypic data, it is concluded that the isolate represents a novel species of the genus Paraburkholderia, for which the name Paraburkholderia caffeinitolerans sp. nov. is proposed. The type strain is CF3T (= LMG 28688T = CGMCC 1.15105T).

[Analysis of the meibomian glands condition in dry eye patients].

OBJECTIVE: To evaluate the condition of meibomian glands in dry eye patients. METHODS: Non interventional, observational study. 388 eyes from 194 patients which were diagnosed as dry eye during March to December 2010 were collected, 69 males (138 eyes), 125 females (250 eyes). Patients' age range 7-85 years, mean (44±18) years. Symptom score, Schirmer test Ia (SIaT), tear film break-up time (BUT) and superficial punctuated keratopathy were measured. The meibomian glands were observed using the noncontact meibography system. RESULTS: In all subjects, symptom score 5.47±2.14, SIaT (5.58±4.22) mm, BUT (3.09±2.34) s, superficial punctuated keratopathy score 4.10±3.79. Meibo-score: 1 point, 3.09% (12 eyes); 2 points, 9.28% (36 eyes); 3 points, 20.10% (78 eyes); 4 points, 26.03% (101 eyes); 5 points, 21.91% (85 eyes); 6 points, 19.59% (76 eyes). CONCLUSIONS: Abnormal meibomian glands occupied a extremely high proportion of dry eye which indicate that meibomian glands disorder plays important role in dry eye. Noncontact meibography system could show accurate structure of meibomian glands.