Hu-Zhang Qing-Mai Formulation anti-oxidative stress alleviates diabetic retinopathy: Network pharmacology analysis and in vitro experiment.

BACKGROUND: In this study, the potential mechanism of the Hu-Zhang Qing-Mai Formulation (HZQMF) on diabetic retinopathy (DR) in inhibiting oxidative stress was explored through network pharmacology analysis and in vitro experiments. METHODS: The Traditional Chinese Medicine Systematic Pharmacology Analysis Platform was used to retrieve the active pharmaceutical ingredients and targets of HZQMF. DR-related genes and oxidative stress-related genes were obtained from PharmGKB, TTD, OMIM, GeneCards, and Drugbank. STRING was used to construct a protein-protein interaction network to screen core targets. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed using R 4.0.3. Network topology analysis was carried out using Cytoscape 3.8.2. Finally, we looked into how well the main API protected human retinal pigment epithelial cells from damage brought on by hydrogen peroxide (H2O2). RESULTS: Quercetin (Que) was identified as the primary API of HZQMF through network pharmacology analysis, while JUN, MAPK1, and STAT3 were identified as the primary hub genes. Kyoto encyclopedia of genes and genomes enrichment analysis showed that the AGE-RAGE signaling pathway may be crucial to the therapeutic process. In vitro experiments confirmed that Que increased cell vitality and inhibited apoptosis. CONCLUSION: Que might significantly reduce H2O2-induced ARPE-19 cell injury by inhibiting apoptosis-related genes of the AGE-RAGE pathway (JUN, MAPK1, STAT3). This study lays the foundation for further research on HZQMF in treating DR.

Mechanisms of Qing-Gan Li-Shui Formulation in Ameliorating Primary Open Angle Glaucoma: An Analysis Based on Network Pharmacology.

Objective: In this study, we investigated the mechanism of Qing-Gan Li-Shui formulation (QGLSF) in treating primary open glaucoma (POAG) by network pharmacology and in vitro experiments. Methods: The active pharmaceutical ingredients (APIs) of GLQSF (prepared with Prunella vulgaris, Kudzu root, Plantago asiatica, and Lycium barbarum) were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Yet Another Traditional Chinese Medicine database (YATCM). The targets of POAG were screened out with GeneCards, OMIM, PharmGKB, Therapeutic Target Database (TTD), and DrugBank databases. The Venny platform was used to summarize the core targets. Topological analysis was performed using Cytoscape3.8.0. A protein-protein interaction network was plotted by STRING online. The key targets were subjected to GO and KEGG enrichment analyses. Finally, the effects of APIs were verified by a model of chloride hexahydrate (CoCl2)-induced retinal ganglion cells-5 (RGC-5). Results: The main APIs were selected as quercetin (Que) by network pharmacology. Nine clusters of QGLSF targets were obtained by the PPI network analysis, including AKT-1, TP53, and JUN. KEGG enrichment analysis showed that these targets were mainly involved in the AGE-RAGE signaling pathway. By in vitro experiments, Que promoted cell proliferation. The secretion of AKT-1, TP53, JUN, AGE, and RAGE in the cell culture supernatant decreased, as shown by ELISA. The mRNA levels of AKT-1, TP53, JUN, and RAGE decreased, as shown by RT-PCR. QGLSF may employ the AGE-RAGE signaling pathway to counter POAG. Conclusion: This study preliminarily elucidates the efficacy and mechanism of QGLSF in the treatment of POAG.

RNAi-mediated knock-down of the dopamine beta-hydroxylase gene changes growth of razor clams.

Dopamine beta-hydroxylase (DßH) plays an essential role in the synthesis of catecholamines (CA) in neuroendocrine networks. In the razor clam, Sinonovacula constricta a novel gene for DßH (ScDßH-α) was identified that belongs to the copper type II ascorbate-dependent monooxygenase family. Expression analysis revealed ScDßH-α gene transcripts were abundant in the liver and expressed throughout development. Knock-down of ScDßH-α in adult clams using siRNA caused a reduction in the growth rate compared to control clams. Reduced growth was associated with strong down-regulation of gene transcripts for the growth-related factors, platelet derived growth factors A (PDGF-A) (P < 0.001) 24 h after ScDßH-α knock-down, vascular endothelial growth factor (VEGF1) (P < 0.001) and platelet derived growth factor B (PDGF-B-2) (P < 0.001) 24 h and 48 h after ScDßH-α knock-down and transforming growth factor beta (TGF-ß1) (P < 0.001) 48 h and 72 h after ScDßH-α knock-down. Taken together the results suggest that the novel ScDßH-α gene through its role in CA synthesis is involved in growth regulation in the razor clam and possibly other bivalves.

Dopamine beta-hydroxylase and its role in regulating the growth and larval metamorphosis in Sinonovacula constricta.

Dopamine beta-hydroxylase (DßH) plays a key role in the synthesis of catecholamines (CAs) in the neuroendocrine regulatory network. The DßH gene was identified from the razor clam Sinonovacula constricta and referred to as ScDßH. The ScDßH gene is a copper type II ascorbate-dependent monooxygenase with a DOMON domain and two Cu2_monooxygen domains. ScDßH transcript expression was abundant in liver and hemolymph. During early development, ScDßH expression significantly increased at the umbo larval stage. Furthermore, the inhibitors and siRNA of DßH were screened. After challenge with DßH inhibitor, the larval metamorphosis and survival rates, and juvenile growth were obviously decreased. Under the siRNA stress, the larval metamorphosis and survival rates were also significantly decreased. Therefore, ScDßH may play an important regulating role in larval metamorphosis and juvenile growth.

Effect of the Meibomian Gland Squeezer for Treatment of Meibomian Gland Dysfunction.

PURPOSE: To investigate the effect of the meibomian gland squeezer for treatment of meibomian gland dysfunction (MGD). METHODS: Seventy patients (140 eyes) with MGD were randomly divided into 2 groups: 36 patients who were treated by the meibomian gland squeezer as the treatment group and 34 patients were selected as the control group. Patients were evaluated at baseline, and 2-week and 1-month visits for subjective symptoms, objective signs and pain assessments, including ocular symptom scores, Ocular Surface Disease Index, tear breakup time, corneal fluorescein staining, Schirmer scores with no anesthetic (Schirmer I test), meibum quality, meibum expressibility, and Numeric Rating Scale-11. RESULTS: Sixty-five patients were followed in the study, and mean (±SD) age was 57.0 (±12.6) years. Compared with baseline, the 2 groups had varying degrees of improvement in ocular symptom scores and Ocular Surface Disease Index at the 2-week and 1-month visits; there was a statistically significant difference between groups (P < 0.001). At the 1-month visit, the treatment group showed a greater improvement in the breakup time (3.8 ± 1.6 vs. 1.8 ± 1.0 seconds, P < 0.001), corneal fluorescein staining (-2.1 ± 2.13 vs. -0.9 ± 1.3, P = 0.03), Schirmer I test (5.3 ± 2.9 vs. 2.3 ± 2.8 mm, P < 0.001), meibum quality (-7.5 ± 2.9 vs. -5.3 ± 2.4, P = 0.004), and meibum expressibility (-1.2 ± 0.8 vs. -0.7 ± 0.4, P = 0.007). In the treatment group, the mean (±SD) of total pain scores was 2.4 ± 1.0, which indicated that mild pain was still predominant under topical anesthesia. CONCLUSIONS: The meibomian gland squeezer may be safe, effective, and helpful for treatment of MGD and may offer an attractive treatment option for some patients with MGD, although it can cause mild pain or discomfort.