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Introduction: Dry eye disease (DED) is a very frequently encountered ocular disease, making it a growing public health burden. However, current treatments for DED present unmet medical needs owing to their side effects or ineffectiveness. Therefore, an effective and safe therapeutic agent to manage DED is needed. Method and Analysis: We planned a phase 2, dose-finding, double-blind, randomized placebo-controlled trial to evaluate the efficacy and safety of two different doses of USL (Useul), the extract of Achyranthis Radix, compared with placebo, for DED. USL has been found to protect against DED by inducing tear secretion and improving corneal irregularity via anti-inflammatory effects, which will provide new therapeutic options. One hundred and twenty participants will be enrolled, after assessing the inclusion/exclusion criteria, at Daejeon University Daejeon Korean Medicine Hospital. Enrolled participants will be allocated to standard-dose USL, high-dose USL, or placebo groups in a 1:1:1 ratio and will be required to administer the trial medication twice a day for 12 weeks and visit the clinic five times. For efficacy outcomes, objective endpoints of fluorescein corneal staining score, tear break-up time, Schirmer's test, and meibomian test and subjective endpoints of Ocular Surface Disease Index, visual analog scale, Standard Patient Evaluation for Eye Dryness-II, and biomarkers will be assessed throughout the trial. Safety will be assessed based on adverse events, vital signs, laboratory tests, visual acuity, and intraocular pressure. Discussion: Our study results are expected to provide clinical evidence for the use of DED as an effective and safe agent for DED. [ABSTRACT FROM AUTHOR]

Age-related ocular diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy are major causes of irreversible vision impairment in the elderly. Conventional treatments focus on symptom relief and disease slowdown, often involving surgery, but fall short of providing a cure, leading to substantial vision loss. Regenerative medicine, particularly mesenchymal stem cells (MSCs), holds promise for ocular disease treatment. This study investigates the synergistic potential of combining placenta-derived MSCs (PD-MSCs) with Achyranthis radix extract (ARE) from Achyranthes japonica to enhance therapeutic outcomes. In a 24-h treatment, ARE significantly increased the proliferative capacity of PD-MSCs and delayed their senescence (* p < 0.05). ARE also enhanced antioxidant capabilities and increased the expression of regeneration-associated genes in an in vitro injured model using chemical damages on human retinal pigment epithelial cell line (ARPE-19) (* p < 0.05). These results suggest that ARE-primed PD-MSC have the capability to enhance the activation of genes associated with regeneration in the injured eye via increasing antioxidant properties. Taken together, these findings support the conclusion that ARE-primed PD-MSC may serve as an enhanced source for stem cell-based therapy in ocular diseases. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence supporting the clinical effectiveness of cooled radiofrequency ablation (RFA) therapy for genicular nerves in patients with chronic knee osteoarthritis (OA) exists. However, no study has been conducted to eliminate the potential influence of a placebo effect associated with this procedure. Therefore, we evaluated the efficacy of cooled RFA compared with a sham procedure in patients with painful knees due to OA. Methods: In this double-blind, randomized, controlled study, participants were randomly assigned to receive cooled RFA of the knee (cooled RFA group, n = 20) or a sham procedure (sham group, n = 20). The primary outcome was the proportion of successful responders at the three-month follow-up. The secondary outcomes were successful responders at one and six months; pain intensity of the knee; functional status; medication; and satisfaction at one, three, and six months after the procedures. Results: For the primary outcome, the successful responder rate was significantly higher in the cooled RFA group (76.5%) than in the sham group (33.3%) (p = 0.018). For the secondary outcome, more successful responders were observed in the cooled RFA group than in the sham group at one and six months after the procedure (p = 0.041 and 0.007, respectively). The decreased knee pain intensity was maintained throughout the six-month follow-up period in the cooled RFA group. No differences were observed in functional status, medication change, or satisfaction in both groups. Conclusions: The cooled RFA of genicular nerves offers significant pain relief and surpasses the effects attributable to a placebo. [ABSTRACT FROM AUTHOR]

Background: Cervical epidural steroid injection is associated with rare but potentially catastrophic complications. The contralateral oblique (CLO) view may be a safe and feasible alternative to the lateral (LAT) view for fluoroscopic-guided cervical epidural steroid injection. However, evidence for the clinical usefulness of the CLO view for cervical epidural steroid injection is lacking. We assessed the clinical usefulness of the CLO view for cervical epidural steroid injection in managing cervical herniated intervertebral discs.Methods: Patients were randomly assigned to receive fluoroscopic-guided cervical epidural steroid injection under LAT view or CLO view at 50±5° degrees groups. The primary outcome was the needling time comparison between the two groups. Secondary outcomes were comparison of first-attempt success rate, needle tip visualization and location, total number of needle passes, final success rate, crossover success rate and false-positive/negative loss of resistance. Complications and radiation dose were also compared.Results: The needling time significantly decreased in the CLO than in the LAT group. The first-attempt success rate was significantly higher in the CLO compared with the LAT group. The needle tip was clearly visualized (p<0.001) and located more often on (or just anterior to) the ventral interlaminar line (p<0.001) in the CLO than in the LAT group. There were significantly fewer needle passes (p=0.019) in the CLO than in the LAT group. There were no significant differences in the final success, crossover success, false-positive/negative loss of resistance or radiation dose between the groups. Two (5.9%) cases in the LAT group experienced complications.Conclusion: The CLO view may be recommended for fluoroscopic-guided cervical epidural steroid injection, considering its better clinical usefulness over the LAT view. [ABSTRACT FROM AUTHOR]

A new isocoumarin (1) named fraxicoumarin was isolated from the bark of Fraxinus chinensis subsp. rhynchophylla along with three known compounds (2–4). The structure of the new compound was established by extensive spectroscopic studies and chemical evidence. The anti-inflammatory effects of the isolated compounds (1–4) on lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells were evaluated in vitro. Of the compounds tested, compounds 1 and 3 inhibited LPS-induced nitric oxide (NO) production in RAW 264.7 cells. Consistent with these findings, they also suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level in RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

Screening drug candidates rapidly is the first step for developing new pharmaceutical drugs. One of the most promising ways to reduce the number of screening steps and cost is to directly use living cells for screening instead of using purified target proteins. Compounds screened using living cells will have increased biological activity compared to those screened with in vitro assays. Here, we report a robust method for screening drug candidates in living cells based on single‐protein imaging. We employed single‐protein tracking to observe the variation in the diffusion coefficient of membrane proteins treated with the candidate compounds. The diffusion coefficient shift was introduced as a criterion for selecting the potential candidate compounds. We tested three different membrane proteins, epidermal growth factor receptor, ErbB2, and ErbB3, and found effective natural compounds for each protein. The screening method we introduce will be widely used for screening potential drug candidates using living cells. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) is a type of air pollutant that poses a risk to human health. In the ocular system, PM causes or aggravates dry eye syndrome (DES) by damaging the corneal and conjunctival epithelia. Liriope platyphylla has been used traditionally as an expectorant, antitussive agent, and tonic in Korea. However, the effects of Liriope platyphylla extract (LPE) on PM-induced ocular damage have not been elucidated. In this study, we evaluated the in vivo protective effect of LPE against PM-induced DES in rats. Topical administration of LPE attenuated the PM-induced decrease in tear volume and reduced corneal epithelial irregularity and damage. LPE also protected against PM-induced disruption of the corneal mucin-4 layer and reduction in the conjunctival goblet cell density. These findings suggest that LPE has protective effects against PM-induced DES. [ABSTRACT FROM AUTHOR]

GS-E3D is an enzymatically modified ginseng extract by pectin lyase. In this study, we evaluated the preventive effects of GS-E3D on blood-retinal barrier (BRB) leakage in a rat model of diabetes. To produce diabetes, rats were injected with streptozotocin. GS-E3D was orally gavaged at 25, 50, and 100 mg/kg body weight for 6 weeks. We then compared the effect of GS-E3D with that of an unmodified ginseng extract (UGE) on retinal vascular leakage. The administration of GS-E3D significantly blocked diabetes-induced BRB breakdown. Immunofluorescence staining showed that GS-E3D reduced the loss of occludin in diabetic rats. In TUNEL staining, the number of apoptotic retinal microvascular cells was dose dependently decreased by GS-E3D treatment. GS-E3D decreased the accumulations of advanced glycation end products in the retinal vessels. In addition, the inhibition potential of GS-E3D on BRB breakage was stronger compared with UGE. These results indicate that GS-E3D could be a beneficial treatment option for preventing diabetes-induced retinal vascular injury. [ABSTRACT FROM AUTHOR]

The Aster koraiensis extract (ASKO) is a newly developed dietary herbal supplement. In this study, the potent blood glucose-lowering activity of ASKO in vitro and in vivo was investigated. In an in vitro glucose uptake assay, ASKO was found to enhance glucose transport in 3T3-L1 adipocytes. Oral administration of ASKO significantly reduced glucose levels in normoglycemic mice during oral glucose tolerance tests (OGTTs). In a long-term efficacy study, 4 weeks of oral ASKO treatment significantly attenuated blood glucose levels during OGTTs in diet-induced obese (DIO) mice. ASKO also enhanced plasma insulin levels after glucose loading, leading to a reduction in blood glucose levels. In addition, ASKO normalized glucose transporter-4 mRNA expression in the muscles of DIO mice. These results indicate that ASKO has postprandial glucose-lowering effects and could be beneficial in the management of prediabetes or type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Many dietary supplements have been sold through advertising their large number of beneficial effects. The aim of this study was to determine whether bilberries ( Vaccinium myrtillus) help to prevent diabetes-induced retinal vascular dysfunction in vivo. V. myrtillus extract (VME; 100 mg/kg) was orally administered to streptozotocin-induced diabetic rats for 6 weeks. All diabetic rats exhibited hyperglycemia, and VME did not affect the blood glucose levels and body weight during the experiments. In the fluorescein-dextran angiography, the fluorescein leakage was significantly reduced in diabetic rats treated with VME. VME treatment also decreased markers of diabetic retinopathy, such as retinal vascular endothelial growth factor (VEGF) expression and degradation of zonula occludens-1, occludin and claudin-5 in diabetic rats. In conclusion, VME may prevent or delay the onset of early diabetic retinopathy. These findings have important implications for prevention of diabetic retinopathy using a dietary bilberry supplement. [ABSTRACT FROM AUTHOR]

Background/Aims: The purpose of the experiment reported here was to assess the involvement of high-mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE) and nuclear factor (NF)-κB signaling pathway in the development of rat diabetic nephropathy. Methods: Diabetes was induced by intraperitoneal streptozotocin injection in 7-week-old male rats. At 20 weeks of age, renal expression of HMGB1 was detected by immunohistochemistry. The expression of RAGE and NF-κB activity was studied by Western blot and electrophoretic mobility shift assay in renal tissues of normoglycemic and diabetic rats, respectively. Results: HMGB1 was highly expressed in both the cytoplasmic and nuclear patterns in diabetic renal glomerular cells and tubular epithelial cells, although in normal rats, HMGB1 was expressed only in the cell nuclei. The expression of RAGE, a potential receptor for HMGB1, and NF-κB activity were also greater in diabetic than in normal rats. Moreover, diabetes increased the binding of NF-κB to the RAGE promoter. Conclusion: These findings suggest that hyperglycemia-induced HMGB1 release may induce the renal injury in diabetic rats, and that the pathogenic role of HMGB1 might be dependent on RAGE and through activation of NF-κB. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]