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Biomed Chromatogr ; : e5235, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553391


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.

Clin Ther ; 43(3): 613-628, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546885


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.

Ciclosporina , Síndromes do Olho Seco , Ciclosporina/efeitos adversos , Método Duplo-Cego , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Soluções Oftálmicas , Método Simples-Cego , Resultado do Tratamento
Int J Ophthalmol ; 12(4): 529-535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024802


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.

Antonie Van Leeuwenhoek ; 109(11): 1475-1482, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27515400


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).

Burkholderiaceae/isolamento & purificação , Cafeína/metabolismo , Microbiologia do Solo , Agricultura , Composição de Bases , Burkholderiaceae/metabolismo , Camellia sinensis , DNA Bacteriano , Tipagem Molecular , Filogenia , RNA Bacteriano , RNA Ribossômico 16S/genética
Zhonghua Yan Ke Za Zhi ; 47(9): 834-6, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-22177132


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.

Síndromes do Olho Seco/diagnóstico , Glândulas Tarsais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Técnicas de Diagnóstico Oftalmológico , Síndromes do Olho Seco/diagnóstico por imagem , Feminino , Humanos , Raios Infravermelhos , Masculino , Glândulas Tarsais/diagnóstico por imagem , Pessoa de Meia-Idade , Radiografia , Adulto Jovem