Characteristics of the Peripapillary Structure and Vasculature in Patients With Myopic Anisometropia.

Purpose: To evaluate the interocular differences of the peripapillary structural and vascular parameters and that of association with axial length (AL) in participants with myopic anisometropia using swept-source optical coherence tomography. Methods: This prospective cross-sectional study included 90 eyes of 45 participants. Each participant's eyes were divided into the more and less myopic eye respectively according to spherical equivalent. The ß- and γ-parapapillary atrophy (PPA) areas, Bruch's membrane opening distance, border length, and border tissue angle were measured manually. Peripapillary choroidal vascularity index and choroidal thickness (CT) values in superior, nasal, inferior, and temporal were calculated using a custom-built algorithm based on MATLAB. Results: The interocular difference in AL and spherical equivalent was 0.62 ± 0.26 mm and -1.50 (-2.13, -1.25) diopters (D), respectively. The interocular difference in spherical equivalent was highly correlated with that of the AL. The ß- and γ-PPA areas were significantly greater in more myopic eyes. The mean and inferior peripapillary choroidal vascularity index and all regions of peripapillary CT were significantly lower in the more myopic eyes. The interocular difference in AL was significantly positively correlated with the interocular differences in γ-PPA area and border length and negatively correlated with the interocular differences in temporal choroidal vascularity index and mean, inferior, and temporal peripapillary CT. There was an independent correlation between the interocular differences in AL and the interocular differences in γ-PPA area, inferior, and temporal peripapillary CT. Conclusions: Significant differences between both groups were detected in most peripapillary parameters, especially in peripapillary CT. The γ-PPA area, border length, and peripapillary CT were significantly correlated with the elongation of AL. Translational Relevance: The current study characterized and analyzed the peripapillary parameters in myopic anisometropia, which helped to monitor myopic progression.

Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a relatively common inflammatory disease that affects the synovial tissue, eventually results in joints destruction and even long-term disability. Although Janus kinase inhibitors (Jakinibs) show a rapid efficacy and are becoming the most successful agents in RA therapy, high dosing at frequent interval and severe toxicities cannot be avoided. Here, we developed a new type of fully compatible nanocarriers based on recombinant chimeric proteins with outstanding controlled release of upadacitinib. In addition, the fluorescent protein component of the nanocarriers enabled noninvasive fluorescence imaging of RA lesions, thus allowing real-time detection of RA therapy. Using rat models, the nanotherapeutic is shown to be superior to free upadacitinib, as indicated by extended circulation time and sustained bioefficacy. Strikingly, this nanosystem possesses an ultralong half-life of 45 h and a bioavailability of 4-times higher than pristine upadacitinib, thus extending the dosing interval from one day to 2 weeks. Side effects such as over-immunosuppression and leukocyte levels reduction were significantly mitigated. This smart strategy boosts efficacy, safety and visuality of Jakinibs in RA therapy, and potently enables customized designs of nanoplatforms for other therapeutics. Electronic Supplementary Material: Supplementary material (further details of DLS analysis, biocompatibility of PCP-UPA, CIA models construction, etc.) is available in the online version of this article at 10.1007/s12274-023-5838-0.

Short-term postoperative changes in the choroidal vascularity index in patients with a unilateral epiretinal membrane.

BACKGROUND: To investigate short-term choroidal structural and vascular changes after epiretinal membrane (ERM) surgery. METHODS: In this retrospective study, 65 patients with unilateral ERM underwent pars plana vitrectomy combined with cataract surgery and were examined one day before surgery and one week, one month, and three months after surgery. Choroidal thickness (CT) and choroidal vascular index (CVI) were evaluated using horizontal enhanced depth imaging optical coherence tomography (EDI-OCT) scans and were further calculated using semi-automatic algorithms using MATLAB R2017a. RESULTS: Preoperatively, CVI was higher in eyes with ERM (61.70 ± 5.17%) than in fellow eyes (59.99 ± 5.26%). CVI increased significantly at one week after surgery (62.14 ± 5.02%) and decreased at 1 and 3 months after surgery (60.76 ± 4.97% and 60.4 ± 4.83%, respectively). The change was pronounced in the nasal region (p < 0.001) and central region (p < 0.05). CT in the temporal macula increased at 1 week (239.65 ± 72.98 µm) after surgery and decreased at 1 and 3 months after surgery (222.15 ± 71.91 µm and 222.33 ± 65.72 µm, respectively; p < 0.01). CONCLUSIONS: Short-term postoperative variations in the choroid have been demonstrated in eyes with ERM. This may be related to the release of macular traction. CVI assessment using EDI-OCT may be a useful tool for investigating choroidal structural changes accompanying ERM and postoperative period.

Effects of Exercise on Optic Nerve and Macular Perfusion in Glaucoma and Normal Subjects.

PRCIS: Using optical coherence tomography angiography, we found an increase in the blood flow in regional macular without significant changes in the optic disk in patients with glaucoma after a moderate exercise regime. PURPOSE: To investigate the effect of moderate exercise on optic nerve and macular perfusion in glaucoma patients. METHODS: Overall, 25 eyes of 25 patients with primary open angle glaucoma and 22 eyes of 22 normal subjects were included in the glaucoma and control groups, respectively. Foveal avascular zone parameters, whole and regional vessel density (VD) in the superficial layer of macula, VDs in the radial peripapillary capillary layer of the optic nerve head, intraocular pressure, and cardiovascular parameters were measured using optical coherence tomography angiography before, immediately after, and 30 minutes after a 20-minute run at moderate speed. RESULTS: In the glaucoma group, macular superficial VD of the whole image, parafovea, and superior and nasal regions were higher after 30 minutes of rest (44.049±5.704, 47.238±5.741, 48.692±6.648, and 47.852±5.078) than immediately after exercise (43.229±5.867, 46.334±5.984, 47.840±6.895, 46.793±5.238, P <0.05). The VD in the temporal and nasal regions was higher 30 minutes after exercise (45.105±5.512 and 47.852±5.078) than before exercise (44.265±5.803 and 46.750±5.639, P <0.05). The intraocular pressure decreased immediately after exercise (14.20±2.51 and 14.51±2.96 mmHg for glaucoma and controls, respectively) but was restored after 30 minutes of rest (15.84±3.57 mmHg for glaucoma and 16.50±2.25 mmHg for controls) in both groups ( P <0.001). Cardiovascular parameters were similar in both groups. CONCLUSION: Moderate physical exercise for 20 minutes increased blood flow in the macula region without significant change to the optic nerve and lowered intraocular pressure in glaucoma and normal subjects. The benefit of these findings to glaucoma patients needs further study.

Characteristics of the Optic Nerve Head in Myopic Eyes Using Swept-Source Optical Coherence Tomography.

Purpose: To investigate the characteristics of the optic nerve head (ONH) in myopia using swept-source optical coherence tomography (SS-OCT). Methods: Participants were divided into three groups according to the axial length (AL). The optic disc morphology, retinal nerve fiber layer (RNFL) thickness, and radial peripapillary capillary (RPC) vessel density (VD), optic disc tilt, rotation, Bruch's membrane opening distance (BMOD), border length (BL), border tissue angle, focal lamina cribrosa (LC) defects, ß- and γ-zone peripapillary atrophy (PPA), microvasculature dropout (MvD), choroidal thickness (CT), and the choroidal vascularity index (CVI) were compared. Linear regression analysis evaluated relationships between spherical equivalent, AL, and ONH parameters. Results: One hundred five, 98, and 118 eyes were included in groups 1, 2, and 3, respectively. With AL increasing, the mean, superior and temporal CT, central mean and temporal, pericentral mean, inferior and nasal RPC VD, and temporal CVI decreased, whereas the mean and temporal RNFL thickness, optic disc, RIM and ß-PPA area, presence and area of γ-PPA, BMOD and BL increased. Compared to other groups, group 3 depicted a larger cup area, more focal LC defect and total and juxtapapillary MvD; a lower central superior, inferior and nasal, pericentral superior, and temporal RPC VD. Group 1 demonstrated more tilted disc, larger inferior and nasal CT, mean, superior, inferior, and nasal CVI. Conclusions: Myopia eyes have larger ONH changes, PPAs, regional RNFL, and MvD, but smaller regional CTs, RPC VD, and CVIs. SS-OCT may be useful in detecting ONH variations during myopia.

Choroidal Vascularity Index Changes After Exercise in Patients With Glaucoma.

Purpose: To investigate the changes in choroidal vascular structures after exercise in patients with glaucoma using an image binarisation algorithm with enhanced-depth imaging optical coherence tomography. Methods: Thirty-four eyes of 19 patients with primary open-angle glaucoma and 40 eyes of 20 normal subjects were included in the glaucoma and control groups, respectively. All subjects were evaluated before, immediately after, and 30 min after 20-min running at moderate speed. The subfoveal choroidal area was segmented into the luminal area (LA) and stromal area (SA), and the choroidal vascularity index (CVI) was measured by calculating the ratio of LA to the total choroidal area (TCA). The mean intraocular pressure (IOP), subfoveal choroidal thickness, CVI, SA, CA, and TCA were compared within and between both groups. The correlation between CVI, IOP, and other vascular indexes was investigated. Results: In the glaucoma group, a significantly lower CVI was found immediately after exercise and recovered 30 min after exercise. Higher TCA and LA levels were demonstrated 30 min after exercise compared to immediately after exercise. In both groups, IOP decreased immediately after exercise but was restored after a 30-min rest. In the glaucoma group, there was a higher correlation between CVI and other choroidal vascular parameters than in the control group. There was no difference in IOP or choroidal parameters between the groups at different time points. Conclusion: In patients with glaucoma, CVI decreased significantly immediately after exercise, indicating that the choroidal layer is affected by exercise and an unhealthy vascular regulatory mechanism.

Potential anti-neuroblastoma agents from Juniperus oblonga.

Neuroblastoma (NB) is a neuroendocrine tumor derived from neural crest cells. Approximately 90% of cases occur in children less than 5 years old. The amplification of MYCN correlates with high-risk neuroblastoma and patients with MYCN amplified showed poorer prognosis than those without MYCN amplification. In this study, three compounds isolated from Juniperus oblonga showed anti-proliferative activity against NB cell lines with and without tetracycline inducible MYCN over-expression which were identified as (-)-deoxypodophyllotoxin (1), (-)-matairesinol (2) and (+)-isocupressic acid (3). The effects of compounds 2 and 3 in NB cells included a decrease in NB cell viability and induction of apoptosis. Compound 1 was more effective in NB cells over-expressing MycN. Compound 1 also showed almost 2-fold induction of intracellular free calcium levels in M2(+) cells, which may indicate a different mechanism of action for this compound. Cytotoxicity studies against the human embryonic kidney cell (HEK-293) showed compounds 1, 2 and 3 were ineffective in the non-cancer cells at concentrations approximating their IC50 against the NB cell lines. These results may lead to safer and more effective treatment options for NB patients especially for those with high-risk NB.

Labdane and Abietane Diterpenoids from Juniperus oblonga and Their Cytotoxic Activity.

A phytochemical investigation of the whole plant of Juniperus oblonga led to the isolationof one previously undescribed labdane diterpenoid, (4R,5S,9S,10R)-13-des-ethyl-13-oxolabda-8(17),11E-dien-19-oic acid (1), together with nine known diterpenoids (2-3, 6-12), two lignans (4, 5),and a coumarin (13). The structures of all the compounds were elucidated on the basis ofspectrometric data, primarily one-dimensional (1D)- and two-dimensional (2D)-NMR and massspectrometry. Electronic circular dichroism (ECD) calculations determined the absoluteconfiguration of 1. In addition, the isolated compounds were evaluated for their cytotoxic activityagainst three human tumor cell lines (HepG2, MCF-7, and HeLa). 6,12-Dihydroxyabieta-5,8,11,13-tetraen-7-one (6) showed moderate cytotoxicity against all three cell lines with IC50 values rangingfrom 24.41 µM to 58.39 µM and trilobinone (10) showed weaker activity with IC50 values rangingfrom 56.93 µM to 79.98 µM. None of the isolated diterpenoids have been previously reported fromJuniperus oblonga, and five compounds are here reported from the genus Juniperus for the first time.

Dihydrophenanthrenes from Juncus effusus as Inhibitors of OAT1 and OAT3.

Organic anion transporters 1 (OAT1) and 3 (OAT3) play important roles in the renal elimination of a range of substrate molecules. Little is known about natural products that can modulate OAT1 and OAT3 activities. The medullae of Juncus effusus is often used for the treatment of dysuria in traditional Chinese medicine. To study the interactions of phytochemicals in J. effusus with human OAT1 and OAT3, a bioactivity guided phytochemical investigation led to seven new phenanthrenoids along with nine known compounds, including eight phenanthrenoids and a benzophenone from the dichloromethane soluble fraction of a methanol extract of the medullae of J. effusus. The structures were established by physical data analysis, including high-resolution electrospray ionization mass spectrometry and 1D and 2D NMR. The compounds were evaluated for inhibition of OAT1 and OAT3 in vitro. Compounds 10 and 16 were inhibitors for OAT1, and compounds 1-3, 10, and 16 were inhibitors for OAT3 with IC50 values less than 5.0 µM. Dihydrophenanthrene 1 markedly altered the pharmacokinetic parameters of the diuretic drug furosemide, a known substrate of both OAT1 and OAT3, in vivo.

Biflavonoids from Juniperus oblonga inhibit organic anion transporter 3.

Organic anion transporters (OATs in humans, Oats in rodents) play an important role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. Their ligand recognition is also important for drug therapy and development. In this study, the n-butanol and dichloromethane soluble fractions of Juniperus oblonga were found to inhibit OAT3 in vitro and three biflavonoids were found to be responsible for this activity. One of these compounds, amentoflavone exhibited stronger inhibition than probenecid, a known strong inhibitor of OAT3. Biological characterization of amentoflavone in vivo also showed inhibition of Oat3. Preliminary observations of structure-activity relationships suggest that the biflavonoids are more potent inhibitors of this transporter than their corresponding monomer, and that methylation of even a single hydroxyl group results in a substantial decrease in activity. This greater potency of the biflavonoids may indicate the need for a more in-depth investigation of the distribution of biflavonoids in plants used as foodstuffs and herbal medicines, due to their potential for causing interactions with OAT3 substrate drugs.

Interactions of 172 plant extracts with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8): a study on herb-drug interactions.

BACKGROUND: Herb-drug interactions (HDIs) resulting from concomitant use of herbal products with clinical drugs may cause adverse reactions. Organic anion transporter 1 (OAT1) and 3 (OAT3) are highly expressed in the kidney and play a key role in the renal elimination of substrate drugs. So far, little is known about the herbal extracts that could modulate OAT1 and OAT3 activities. METHODS: HEK293 cells stably expressing human OAT1 (HEK-OAT1) and OAT3 (HEK-OAT3) were established and characterized. One hundred seventy-two extracts from 37 medicinal and economic plants were prepared. An initial concentration of 5 µg/ml for each extract was used to evaluate their effects on 6-carboxylfluorescein (6-CF) uptake in HEK-OAT1 and HEK-OAT3 cells. Concentration-dependent inhibition studies were conducted for those extracts with more than 50% inhibition to OAT1 and OAT3. The extract of Juncus effusus, a well-known traditional Chinese medicine, was assessed for its effect on the in vivo pharmacokinetic parameters of furosemide, a diuretic drug which is a known substrate of both OAT1 and OAT3. RESULTS: More than 30% of the plant extracts at the concentration of 5 µg/ml showed strong inhibitory effect on the 6-CF uptake mediated by OAT1 (61 extracts) and OAT3 (55 extracts). Among them, three extracts for OAT1 and fourteen extracts for OAT3 were identified as strong inhibitors with IC50 values being <5 µg/ml. Juncus effusus showed a strong inhibition to OAT3 in vitro, and markedly altered the in vivo pharmacokinetic parameters of furosemide in rats. CONCLUSION: The present study identified the potential interactions of medicinal and economic plants with human OAT1 and OAT3, which is helpful to predict and to avoid potential OAT1- and OAT3-mediated HDIs.