Treatment of Netherton Syndrome With Abrocitinib.

This case report describes a 28-year-old woman with Netherton syndrome who had large erythematous migratory patches with serpiginous double-edged scales on her face, neck, trunk, and extremities.

Circ_0084043-miR-134-5p axis regulates PCDH9 to suppress melanoma.

The low survival rates, poor responses, and drug resistance of patients with melanoma make it urgent to find new therapeutic targets. This study investigated whether the circ_0084043-miR-134-5p axis regulates the antitumor effect of protocadherin 9 (PCDH9) in melanoma. Ectopic expression or knock down (KD) of PCDH9 with a lentivirus vector, we explored its effects on the proliferation, invasion, and apoptosis of melanoma and verified its regulatory effect on ras-related C3 botulinum toxin substrate 1 (RAC1), proline-rich tyrosine kinase 2 (Pyk2), Cyclin D1, matrix metalloproteinase 2 (MMP2), and MMP9. We further observed the effect of KD circ_0084043 on the malignant behavior of melanoma and studied whether circ_0084043 sponged miR-134-5p and regulated PCDH9. We found that circ_0084043 was overexpressed in melanoma and associated with the malignant phenotype. PCDH9 was poorly expressed in human melanoma tissues, and overexpression of PCDH9 inhibited melanoma progression. Quantitative real-time PCR and Western blotting results showed that overexpression of PCDH9 could downregulate RAC1, MMP2, and MMP9 and upregulate Pyk2 and Cyclin D1. Circ_0084043 KD inhibited invasion and promoted apoptosis in melanoma cells. Circ_0084043 could sponge miR-134-5p and thus indirectly regulate PCDH9. Furthermore, we discovered that inhibiting circ_0084043 had an anti-PD-Ll effect. In vivo, PCDH9 overexpression inhibited melanoma tumor growth, but PCDH9 KD promoted it. In conclusion, PCDH9, which is regulated by the circ 0084043-miR-134-5p axis, can suppress malignant biological behavior in melanoma and influence the expression levels of Pyk2, RAC1, Cyclin D1, MMP2, and MMP9.

The role of estrogen in circular RNA and metabonomics in a Neisseria gonorrhoeae infection model.

Background: Previous study shows that estrogen exerts both immunosuppressive and immunostimulative effects. Methods: In this study, estrogen was added to a Neisseria gonorrhoeae infection model, and transcriptome sequencing and metabolomics studies were performed to clarify the changes in circular RNA (circRNA) and metabolic pathways regulated by the addition of estrogen. Results: The results showed that following the addition of estrogen to the gonococcal infection model, the expression of circRNAs was up-regulated and the expression of circRNAs was down-regulated. In the metabolic group, it was found that after the addition of estrogen, the expression of nine metabolites was down-regulated and 61 metabolites were up-regulated. Furthermore, through network interaction analysis of differentially-expressed circRNAs and differentially-expressed metabolites, we found that the top 10 significantly related metabolites and circRNA were 2-Epoxybutane/novel_circ_0024520; 1,2-Epoxybutane/novel_circ_0061793; 2-Imino-4-methylpiperidine/novel_circ_0012178; 2-Imino-4-methylpiperidine/novel_circ_0056959; Acetone oxime/novel_circ_0012178; Adifoline/novel_circ_0012178; CARBETAPENTANE/novel_circ_0054387; CARBETAPENTANE/novel_circ_0056959; deoxy-PF1140/mmu_circ_0000397; and Methyl (2E,6Z)-dodecadienoate/novel_circ_0012178. Among these, CARBETAPENTANE/novel_circ_0054387 and CARBETAPENTANE/novel_circ_0056959 were positively correlated, while the remaining metabolites were negatively correlated. Conclusions: In this study, high-throughput sequencing and metabolomics mass spectrum were applied to screen the differentially-expressed circRNAs and metabolites regulated by estrogen, which will help to provide new research ideas and indicators for asymptomatic infections in women, and can be meaningful for the relevant study in the future.

Identification and functional annotation of differentially expressed long noncoding RNAs in retinoblastoma.

Retinoblastoma (RB), the most common intraocular malignancy, typically occurs in pediatric patients under the age of 6 years. The present study aimed to explore the long noncoding RNA (lncRNA) expression profile in RB and identify novel lncRNA biomarkers to facilitate the investigation of molecular mechanisms of RB and improve clinical therapy. Raw microarray data for the comparison of gene expression between three RB and three adjacent normal tissue samples were downloaded from Gene Expression Omnibus (dataset no. GSE111168). After identification of differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) in RB, functional enrichment analyses and a DEL-DEM weighted correlation network analysis were performed. A total of 3,915 DELs (1,774 upregulated and 2,141 downregulated) and 3,715 DEMs (1,492 upregulated and 2,223 downregulated) were identified in RB. The DEL-targeted DEMs were highly enriched by genes involved in hexose transport, muscle tissue morphogenesis, the stereocilium membrane, endothelin B receptor binding and γ-filamin/ABP-L, α-actinin and telethonin binding protein of the Z-disc binding. Furthermore, associations of the DELs and DEMs with several pathways were determined, including PI3K/AKT, Hippo and cancer signaling, as well as extracellular matrix-receptor interaction pathways. Coexpression network analysis revealed that the top three DELs, lnc-DAZ1-161, lnc-HDAC7-21 and lnc-OR52A1-55, formed coexpression modules with 181, 156 and 210 DEMs, respectively. In addition, the top three DEMs, namely EIF1AY, GSTM1 and NLRP11, formed coexpression modules with 33, 50 and 41 DELs, respectively. Validation using reverse transcription-quantitative PCR indicated that the expression of representative lncRNAs (lnc-DAZ1-161 and lnc-HDAC7-21) in RB cells in vitro was consistent with that in RB tissues in the database, while the expression of lnc-OR52A1-55 was not consistent with the database. These results suggested that the aberrant lncRNA expression profile in RB is related to the differential regulation of numerous physiological and pathological processes. The lncRNA and mRNA profiles in RB identified may provide novel targets for the investigation of its molecular mechanisms and thus lead to improvements in clinical therapy for RB.

Comparative study on optic disc features of premature infants and full-term newborns.

BACKGROUND: To study optic disc features of premature infants and compare to that of term infants to explore the pattern and features of newborn optic disc development and provide the basis for the diagnosis of newborn optic disc disease. METHODS: This was a prospective clinical research. Newborns underwent newborn fundus disease screening from January 1st, 2016 to October 31st, 2016 in the neonatal ward of Ruian City Maternal and Child Health Hospital were selected. RetCam 3 Version6.1.25.0 Wide-Field Digital Pediatric Retinal Imaging System developed by Clarity Medical Systems, Inc was adopted to conduct fundus examination on both eyes, 130 degree wide-angle lens was used to film the images centering optic disc. RESULTS: For both premature infants and full-term newborns, vertical diameter of the optic disc to lateral diameter of the optic disc ratio was > 1, and the shape of the optic disc was a vertical oval. The difference of each optic disc parameter between premature infants and full-term newborns was not statistically significant (P > 0.05). There's a difference of constitution of sclerotic ring type on optic disc between premature infants and full-term newborns. Among which, the proportion of single ring type and double ring type in premature infants was higher than that in full-term newborns (P < 0.05). The proportion of no ring type in full-term newborns was higher than that in premature infants (P < 0.05). The proportion of mixed type had no significant difference (P > 0.05) between premature infants and full-term newborns. CONCLUSIONS: We found that The proportion of mature types (single ring type and double ring type) in full-term newborns was higher than that in premature infants. While there's no statistical difference of the proportion of mixed types between premature infants and full-term newborns. Double ring type was a normal stage of the development of optic disc.

High-Performance Intraocular Biosensors from Chitosan-Functionalized Nitrogen-Containing Graphene for the Detection of Glucose.

The noninvasive and real-time detection of glucose sugar from tears is promising for the early diagnosis and treatment of chronic diseases such as diabetes. However, its realization is a big challenge. A suitable biosensor electrode that can closely fit the eye and be electrochemically sensitive is still unrealized. In this work, nitrogen-doped graphene (N-G) was used as an ophthalmic electrode in a high-performance intraocular biosensor. The use of N-G has been reported elsewhere before as it is highly electroactive and so has a particular use in biosensors. We hereby present a novel procedure for making carboxylated chitosan-functionalized nitrogen-containing graphene (GC-COOH) by using a one-step ball-milling process. This process does not use toxic chemicals, flammable gases, or a high temperature. It is thus particularly easy to perform. The fabricated nanomaterial had a high electroactivity and was easily assembled as a glucose biosensor by the immobilization of glucose oxidase. The thus constructed biosensor has a high sensitivity at 9.7 µA mM-1 cm-2, a broad linear range at 12 mM, and a good detection limit of 9.5 µM. It was able to maintain this activity after a month of storage. We also report the intraocular use of this constructed biosensor. The as-prepared GC-COOH was found to be highly biocompatible to ophthalmologic cells such as corneal epithelial and retinal pigment epithelium cells. No change in the intraocular pressure or the corneal structure was measured in a New Zealand white rabbit model. The as-assembled sensor was worn by the animals for more than 24 h without undue impact. This result confirmed the biosensor's potential for intraocular application in the clinic. Its assembly into a useful sensor shown here has great potential to provide real-time monitoring of glucose levels in tear fluids of patients with high sugar levels.

Characteristics of Neovascularization in Early Stages of Proliferative Diabetic Retinopathy by Optical Coherence Tomography Angiography.

PURPOSE: To classify retinal neovascularization in untreated early stages of proliferative diabetic retinopathy (PDR) based on optical coherence tomography angiography (OCTA). DESIGN: A cross-sectional study. METHODS: Thirty-five eyes were included. They underwent color fundus photography, fluorescein angiography (FA), and OCTA examinations. Neovascularizations elsewhere (NVEs), neovascularizations at the disc (NVDs), and intraretinal microvascular abnormalities (IRMAs) were scanned by OCTA. The origin and morphology of NVE/NVD/IRMA on OCTA were evaluated. Retinal nonperfusion areas (NPAs) were measured using ImageJ software. RESULTS: In 35 eyes successfully imaged, 75 NVEs, 35 NVDs, and 12 IRMAs were captured. Three proposed subtypes of NVE were identified based on the origins and morphologic features. Type 1 (32 of 75, 42.67%) originated from the venous side, in a tree-like shape. Type 2 (30 of 75, 40.00%) originated from capillary networks, with an octopus-like appearance. Type 3 (13 of 75, 17.33%) originated from the IRMAs, having a sea fan shape. NVD originated from the retinal artery, from the retinal vein, or from the choroid, and arose from the bending vessels near the rim of the optic disc. IRMA originated from and drained into retinal venules, extending into the retina. The initial layer and affiliated NPA were significantly different in the 3 subtypes of NVEs (all P < .01). CONCLUSIONS: OCTA allowed identification of the origins and morphologic patterns of neovascularization in PDR. The new classification of retinal neovascularization may be useful to better understand pathophysiological mechanisms and to guide efficient therapeutic strategies.

Cytotoxicity and genotoxicity of bacterial magnetosomes against human retinal pigment epithelium cells.

A variety of nanomaterials have been developed for ocular diseases. The ability of these nanomaterials to pass through the blood-ocular barrier and their biocompatibility are essential characteristics that must be considered. Bacterial magnetosomes (BMs) are a type of biogenic magnetic nanomaterials synthesized by magnetotactic bacteria. Due to their unique biomolecular membrane shell and narrow size distribution of approximately 30 nm, BMs can pass through the blood-brain barrier. The similarity of the blood-ocular barrier to the blood-brain barrier suggests that BMs have great potential as treatments for ocular diseases. In this work, BMs were isolated from magnetotactic bacteria and evaluated in various cytotoxicity and genotoxicity studies in human retinal pigment epithelium (ARPE-19) cells. The BMs entered ARPE-19 cells by endocytosis after a 6-h incubation and displayed much lower cytotoxicity than chemically synthesized magnetic nanoparticles (MNPs). MNPs exhibited significantly higher genotoxicity than BMs and promoted the expression of Bax (the programmed cell death acceleration protein) and the induction of greater cell necrosis. In BM-treated cells, apoptosis tended to be suppressed via increased expression of the Bcl-2 protein. In conclusion, BMs display excellent biocompatibility and potential for use in the treatment of ocular diseases.

Multifunctional glucose biosensors from Fe3O4 nanoparticles modified chitosan/graphene nanocomposites.

Novel water-dispersible and biocompatible chitosan-functionalized graphene (CG) has been prepared by a one-step ball milling of carboxylic chitosan and graphite. Presence of nitrogen (from chitosan) at the surface of graphene enables the CG to be an outstanding catalyst for the electrochemical biosensors. The resulting CG shows lower ID/IG ratio in the Raman spectrum than other nitrogen-containing graphene prepared using different techniques. Magnetic Fe3O4 nanoparticles (MNP) are further introduced into the as-synthesized CG for multifunctional applications beyond biosensors such as magnetic resonance imaging (MRI). Carboxyl groups from CG is used to directly immobilize glucose oxidase (GOx) via covalent linkage while incorporation of MNP further facilitated enzyme loading and other unique properties. The resulting biosensor exhibits a good glucose detection response with a detection limit of 16 µM, a sensitivity of 5.658 mA/cm(2)/M, and a linear detection range up to 26 mM glucose. Formation of the multifunctional MNP/CG nanocomposites provides additional advantages for applications in more clinical areas such as in vivo biosensors and MRI agents.

Ocular biocompatibility evaluation of hydroxyl-functionalized graphene.

We have presented our recent efforts on genotoxicity and intraocular biocompatibility of hydroxylated graphene (G-OH) prepared by ball milling. We have previously demonstrated that the as-synthesized G-OH could be considered as an excellent alternative for graphene oxide which had been applied widely. Following our last report on G-OH, we carried out detailed studies on genotoxicity and in vivo biocompatibility of G-OH in this work. Less than 5% enhanced caspase-3 level was observed for cells exposed to more than 50 µg/mL G-OH over 72 h, suggesting G-OH caused cell apoptosis was slight. The G-OH induced DNA damage was also found to be mild since expression of p53 and ROS regeneration level was quite low even at high concentration of G-OH over a long time. Cell viability was found to be higher than 90% with 50 µg/mL G-OH and 80% with 100 µg/mL G-OH using flow cytometry. Comet results suggested that less than 5% tail could be found with 100 µg/mL G-OH. TEM results confirmed that G-OH could penetrate into and out of the cytoplasm by means of endocytosis and exocytosis without causing damage on cell membranes. In vivo biocompatibility of G-OH was studied by intravitreal injection of G-OH into rabbits. The ocular fundus photography results showed that G-OH could be diffused in the vitreous body gradually without any damage caused. Injection of G-OH had caused few damages on eyesight related functions such as intraocular pressure, electroretinogram and histological structures of the retina.

[A design of refractometer based on blur circle].

OBJECTIVE: Design a convenient and stable eye refractometer based on the theory of blur circle. METHODS: Analyze the retinal blur circle in both Emsly reduced eye model and Liou & Brennan 1997 eye model by ZEMAX. Design the coefficients including PD (pupil diameter) and NO' (length between node point and fovea) with the purpose of improving the accuracy. At last, compare the clinical optometry data from this refractor with the data obtained from optometry hospital in Wenzhou. RESULTS: The blur circle diameters are nearly the same in both reduced eye model and the Liou & Brennan 1997 eye model. With the PD = 4 mm and NO' = 20 mm, the refractor shows a fine accuracy in optometry. The paired t test shows that the myopia group and the astigmatism axial direction group have no statistical difference between the data from the blur circle refractor and the hospital (P > 0.05), while the astigmatism degree group has the result of P = 0.41 which may be caused by the poor cooperation of pediatric patients. 80% of the astigmatism degree data differ from the data from the hospital in less than 0.75D. CONCLUSION: The blur circle refractor, with the features of convenience and fine accuracy, is promised to be a new style of refractometer in the future.