Clinical Usefulness of BACT Count and BACT-Info Flag of UF-5000 for Screening for Urinary Tract Infection and Prediction of Gram-Negative Bacteria.

BACKGROUND: A rapid and reliable screening test for urinary tract infection (UTI) is needed to reduce the turn-around time and to rule out negative results of urine culture. The aim of this study was to evaluate the performance of BACT count and BACT-Info flag of the UF-5000 for screening for UTI. METHODS: A total of 1,063 urine specimens from April to September 2019 were included in this study. We evaluated the diagnostic performance of white blood cell (WBC) count, BACT count, BACT-Info flag, and UTI flag in UF-5000 by comparing with the urine culture results. RESULTS: Of the urine specimens, 16.7% were culture-positive (≥ 105 CFU/mL) with 15 being yeast positive. A BACT count of > 685.3/µL showed the best diagnostic performance with 93.8% sensitivity and 90.2% specificity. We confirmed that the combination of BACT count (685.3/µL) and BACT-Info flag would be appropriate to use in a clinical laboratory (sensitivity 91.5%, specificity 90.5%). Based on this combination, the sensitivity and specificity of the Gram-negative flag were 95.5% and 94.8%. CONCLUSIONS: We recommend the use of a combination of BACT count (685.3/µL) and BACT-Info for UTI diagnosis. This combination is more appropriate for Gram-negative bacteria, and it would be useful for selecting empirical treatment.

Sulglycotide ameliorates inflammation in lipopolysaccharide-stimulated mouse macrophage cells by blocking the NF-κB signaling pathway.

Objective: Several studies demonstrated that sulglycotide has anti-inflammatory and anti-cancer effects. However, the effect of sulglycotide is limited to gastric mucosal tissues and cells and underlying molecular mechanisms are not clear. This study estimated the effect of sulglycotide on lipopolysaccharide (LPS)-induced inflammatory responses in the macrophage cell line, RAW 264.7 and elucidated the molecular mechanisms. Materials and methods: The inhibitory effect of sulglysotide on LPS-induced oxidative stress and inflammatory reactions were determined by Immunofluorescence staining, ELISA, Western blotting and RT-PCR. Results: Our results show that sulglycotide has the ability to inhibit inflammatory mediators and cytokine production as well as reactive oxygen species (ROS) generation. This effect can be the result from regulating the activation of nuclear factor-kappa B (NF-κB) through blocking mitogen-activated protein kinase (MAPK) intracellular signaling pathways. Conclusions: These results indicate that sulglycotide could be an anti-inflammatory and anti-oxidative compound that may be a useful candidate for treatment of inflammatory diseases.

Quercetin Mitigates Inflammatory Responses Induced by Vascular Endothelial Growth Factor in Mouse Retinal Photoreceptor Cells through Suppression of Nuclear Factor Kappa B.

Retinal vascular endothelial growth factor (VEGF) increased by neovascularization is well known as a pathogenic factor in ocular neovascular diseases. However, it is still unclear how retinal neurons are damaged by VEGF. The aims of this study are to demonstrate the inflammatory protein expression regulated by VEGF using mouse photoreceptor-derived cells and the protective effect of quercetin against VEGF-induced inflammatory response. Expression and phosphorylation of protein and expression of mRNA were detected by immunoblot and reverse transcriptase polymerase chain reaction. VEGF-induced degradation of limiting membrane and translocation of nuclear factor kappa B (NF-κB) were analyzed by immunocytochemistry. VEGF treatment activated angiogenic signaling pathway in photoreceptor cells. In addition, adhesion molecules and matrix metalloproteinases were increased in VEGF-treated photoreceptor cells. All these events were reversed by quercetin. Zona occludins-1 and ß-catenin decreased by VEGF were recovered by quercetin. NF-κB signaling pathway regulated by VEGF through phosphorylations of mitogen-activated protein kinases (MAPK) and protein kinase B (Akt) was suppressed by quercetin. These results suggest that quercetin suppressed VEGF-induced excessive inflammatory response in retinal photoreceptor cells by inactivation of NF-κB signals through inhibition of MAPKs and Akt. These data may provide a basic information for development of pharmaceuticals or nutraceuticals for treatment of retinal diseases caused by excessive VEGF.

Chondrocyte-derived extracellular matrix suppresses pathogenesis of human pterygium epithelial cells by blocking the NF-κB signaling pathways.

PURPOSE: We previously have reported that chondrocyte-derived extracellular matrix (CDECM) suppresses the growth of pterygium in athymic nude mice. The aim of this study is to demonstrate the effect of CDECM on the pterygium epithelial cells and molecular signaling pathways in human primary pterygium epithelial cells (hPECs). METHODS: Human conjunctival epithelial cells (hConECs) were used for identification of the effect of CDECM on normal conjunctiva. The effects of CDECM on proliferation were measured with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfenyl)-2H-tetrazolium (MTS) assay. Cell migration was evaluated according to the scratch wound closure assay and the Transwell invasion assay. Pterygium-related angiogenesis, inflammation, and extracellular matrix remodeling were analyzed with immunoblot and enzyme-linked immunosorbent assay (ELISA). The level of oxidative stress was detected with 2',7'-dichlorofluorescein diacetate (DCFH-DA). Protein kinase signaling was also analyzed with immunoblot. RESULTS: CDECM did not show cytotoxicity until 1 mg/ml in the hConECs and hPECs. Cell migration and invasion were markedly reduced by treatment of 1 mg/ml CDECM in the hPECs to 34% of the control, but not in the hConECs. CDECM significantly downregulated matrix metallopeptidase 9 (MMP-9) and fibronectin and upregulated tissue inhibitor of metalloprotease 1 (TIMP-1) and -2 in the hPECs. Angiogenic factors, such as vascular endothelial growth factor (VEGF), antivascular cellular adhesion molecule 1 (VCAM-1), and cluster of differentiation 31 (CD31), and proinflammatory factors, including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox2), interleukin 6 (IL-6), and prostaglandin E2 (PGE2), were dramatically reduced by CDECM in the hPECs. Furthermore, CDECM significantly inhibited the generation of intracellular reactive oxygen species and the expression of NADPH oxidase subunits, Nox2 and p47phox. CDECM induced nuclear factor erythroid-2 related factor 2 (Nrf2) mediated-antioxidant enzyme heme oxygenase-1 (HO-1). CDECM also suppressed nuclear factor-kappa B (NF-κB) activation and the phosphorylation of p38 mitogen-activated protein kinase (MAPK), protein kinase C alpha (PKCα), and PKCθ. CONCLUSIONS: CDECM was markedly effective in pathogenesis of hPECs. CDECM-suppressed migration of hPECs resulted from the inhibition of NF-κB activation and the improvement of Nrf2 induction by blocking the p38 MAPK and PKC signaling pathways.

Inhibitory effects of the platelet-activating factor receptor antagonists, CV-3988 and Ginkgolide B, on alkali burn-induced corneal neovascularization.

PURPOSE: Platelet-activating factor (PAF) has been found in various ocular tissues; the activity of PAF depends on the binding to its specific receptor, PAF-receptor. We investigated the therapeutic effects of PAF-receptor antagonists (CV-3988 and Ginkgolide B) on alkali burn-induced corneal neovascularization (CNV). METHODS: CNV was induced by applying a 0.2 N sodium hydroxide (3 µl, NaOH) solution directly on mice corneas. CV-3988 (1 mM/10 µl) and Ginkgolide B (1 mM/10 µl) were administered topically on the corneas three times daily for three consecutive days. CNV was evaluated under a slit-lamp microscope. Corneas were processed for histological, immunohistochemical and reverse transcription polymerase chain reaction analysis. Human umbilical vein endothelial cells were used for the migration and tube formation assay. RESULTS: Application of CV-3988 and Ginkgolide B inhibited CNV caused by alkali burn. CV-3988 and Ginkgolide B attenuated the expression of PAF-receptor mRNA. Alkali injury induced a massively increased intraocular mRNA expression of an angiogenic factor in cornea tissues, whereas these increments were attenuated by the application of CV-3988 and Ginkgolide B. CONCLUSIONS: CV-3988 and Ginkgolide B reversed opacity and neovascularization in alkali burn-induced corneas. Our findings suggest that CV-3988 and Ginkgolide B may be therapeutically useful in the treatment of CNV and inflammation.

Caffeic acid phenethyl ester inhibits the inflammatory effects of interleukin-1ß in human corneal fibroblasts.

CONTEXT: Expression of various inflammatory mediators in corneal fibroblasts contributes to corneal inflammation. OBJECTIVE: The purpose of this study was to assess the possible effects of caffeic acid phenethyl ester (CAPE) on the expression of inflammatory mediators during an inflammatory response in human corneal fibroblasts. MATERIALS AND METHODS: The levels of interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule-1 (ICAM-1) from IL-1ß-exposed human corneal fibroblasts were measured with enzyme-linked immunosorbent assays (ELISA). The regulatory mechanisms of CAPE on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. A functional validation was carried out by evaluating the inhibitory effects of CAPE on neutrophil and monocyte migration in vitro. RESULTS: CAPE inhibited the expression of IL-6, MCP-1 and ICAM-1 induced by the pro-inflammatory cytokine IL-1ß in corneal fibroblasts. The activation of AKT and NF-κB by IL-1ß was markedly inhibited by CAPE, whereas the activity of mitogen-activated protein kinases (MAPKs) was not affected. CAPE significantly suppressed the IL-1ß-induced migration of differentiated (d)HL-60 and THP-1 cells. DISCUSSION: These anti-inflammatory effects of CAPE may be expected to inhibit the infiltration of leukocytes into the corneal stroma in vivo.

Frozen Block Tissue Staining for Eye Structure of Zebrafish Embryo.

Histology is a technique used to study the morphology of cell structures by cutting samples into thin sections. Histological cross-section and staining are the techniques needed to visualize the morphology of cell tissues. A suitable tissue staining experiment was created to observe changes in the retinal layer in zebrafish embryos. Zebrafish have a human-like visual system, retina, and eye structures. Due to the small size of zebrafish and undeveloped bones in the embryonic stage, the resistance through cross-section is inevitably small. Here, we present optimized protocol changes in eye tissue of zebrafish using frozen blocks.

Comparison of experimental porous silicone implants and porous silicone implants.

BACKGROUND: To investigate the extent and pattern of fibrovascular ingrowth of porous silicone sphere implants compared to porous polyethylene implants. METHODS: Experimental porous silicone sphere implants and porous polyethylene implants were implanted in the left socket of 20 New Zealand white rabbits after enucleation. Fibrovascular ingrowth and maturation was evaluated at 4 weeks and 8 weeks after implantation by histopathologic examination and scanning electron microscope. RESULTS: At 4 weeks after surgery, porous polyethylene implants showed deeper fibrovascular ingrowth than porous silicone sphere implants; 42.4% versus 34.2% of radius of the implants respectively (p = 0.047). However there was no significant difference in the depth of fibrovascular ingrowth between the two groups at 8 weeks after implantation, although porous polyethylene implants showed deeper fibrovascular ingrowth than porous silicone sphere implants; 71.6% versus 63.6% (p = 0.102). CONCLUSIONS: Porous silicone orbital implants demonstrated a comparable extent of fibrovascular ingrowth to that for porous polyethylene implants. Therefore, this new porous silicone sphere implant may be a good candidate to substitute for current porous implants at a lower cost.

HL3501, a Novel Selective A3 Adenosine Receptor Antagonist, Lowers Intraocular Pressure (IOP) in Animal Glaucoma Models.

PURPOSE: The A3 adenosine receptor (A3AR) is a known therapeutic target for glaucoma treatment. In this study, we developed HL3501 and examined its selectivity profile and in vitro and in vivo effects. METHODS: For the rabbit model, intraocular pressure (IOP) was increased by laser photocoagulation of the trabecular meshwork (TM). The rabbits were then topically treated with HL3501, latanoprost, timolol, or vehicle for 3 weeks. For the mouse model, HL3501, latanoprost, or vehicle was administered following induced IOP elevation by dexamethasone (Dex). The IOP of all rabbits and mice was measured. Electroretinography was performed on both eyes of dark-adapted anesthetized mice on days 0 and 21. The mice's eyes were enucleated at the end of the treatment for immunofluorescence staining. RESULTS: HL3501 was highly specific to the A3AR and inhibitory of A3AR function. In the rabbit glaucoma model, HL3501 and latanoprost significantly decreased the IOP. In the Dex-treated mouse model, HL3501 and latanoprost significantly decreased the IOP and increased the b-wave amplitude as compared with the vehicle treatment. HL3501 and latanoprost also inhibited fibronectin and α-smooth muscle actin expression induced by Dex treatment. CONCLUSIONS: HL3501 had effects similar to those of latanoprost in reducing ocular hypertension in animal models. HL3501 could be used as a novel approach to treat glaucoma. TRANSLATIONAL RELEVANCE: HL3501 is a novel preclinical compound targeting the A3 adenosine receptor, which may also be a new treatment option to fill the unmet needs of many glaucoma patients.

The pharmacokinetics of enteric-coated mycophenolate sodium and its gastrointestinal side effects in de novo renal transplant recipients of Hispanic ethnicity.

OBJECTIVE: The aim of the study is to characterize the pharmacokinetics and the gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC-MPS) in de novo kidney transplant patients of Hispanic ethnicity. MATERIALS AND METHODS: The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney transplant patients of Hispanic ethnicity. Eight blood samples were obtained after EC-MPS was given at the steady state. Blood concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were measured. RESULTS: The mean age (± standard deviation) was 39.4 (± 12.3) years. The mean daily dose of EC-MPS at the time of the pharmacokinetic study was 1408 ± 108 mg. For MPA and MPAG, the time to peak concentration was 2.5 ± 1.3 hours and 4.6 ± 3.1 hours, respectively; the peak concentration (Cmax) was 19.3 ± 17.2 mg/L and 109.4 ± 49.2 mg/L; and the area under the curve from 6 to 12 hours (AUC6-12) was 32.2 ± 19.3 mg·hr/L and 373.7 ± 235.8 mg·hr/L, respectively, which represents 41.3% and 43.0% of AUC0-12. The AUC0-12 for MPA measured 77.8 ± 53.1 mg·hr/L and for MPAG 869.2 ± 388.8 mg·hr/L. Seven patients (64%) exhibited a second peak at approximately 8.3 hours after the dose at a mean concentration (± standard deviation) of 10.3 ± 7.6 mg/L. The Cmax or AUC of MPA does not correlate with overall Gastrointestinal Symptom Rating Scale scores or subscale scores, but the Cmax of MPAG correlates with indigestion subscale (P = 0.022), diarrhea (P = 0.032), and overall scores (P = 0.028). The AUC of MPAG also correlates with acid reflux (P = 0.024) and indigestion (P = 0.032). DISCUSSION AND CONCLUSION: The pharmacokinetics of EC-MPS has a high variability in de novo kidney transplant patients of the Hispanic ethnicity, which was similar to other ethnic groups. The MPA exposure expressed by the AUC appears to be higher in Hispanic patients than those reported in other ethnic groups, which may be the result of various factors such as difference of the uridine diphosphate glucuronosyltransferase enzyme genotypes, but gastrointestinal side effects were acceptable and the Cmax or AUC of MPAG showed correlations with gastrointestinal symptoms.

Development of a zebrafish screening model for diabetic retinopathy induced by hyperglycemia: Reproducibility verification in animal model.

This study aimed at creating a zebrafish screening model for diabetic retinopathy, and evaluated the effects of aflibercept, which is being used to treated diabetic retinopathy. A morphological change occurred at 160 mM of glucose. The survival and hatching rate decreased in a dose-dependent manner. In the 130 mM glucose group, the retinal vessel diameter was more than double that in the normal group. The zebrafish embryo morphology changed in 200 µg/mL and 400 µg/mL at aflibercept. The survival and hatching rate decrease at 400 µg/mL. Aflibercept 100 µg/mL was a nontoxic and effective dose for the zebrafish diabetic retinopathy model. The expression of diabetic retinopathy inflammatory markers was increased in hyperglycemia. But the inflammation was improved by aflibercept in the zebrafish eye. In a zebrafish diabetic retinopathy model, the diameters of retinal vessels were reduced after treatment with aflibercept, and molecular biological and histopathological efficacy was confirmed. This model can serve for screening of new drug candidates for treatment of in diabetic retinopathy.

Cevimeline-induced anti-inflammatory effect through upregulations of mucins in the ocular surface of a dry eye mouse model.

This study aimed to investigate the effects of various concentrations of cevimelines (CVMs) and compare them with commercial drugs in a murine model of dry eye. The experimental mouse model used male and female NOD.B10.H2b mice over 12 weeks of age. Desiccation stress was performed at 30-40% ambient humidity, and subcutaneous injection of 0.5 mg/0.2 mL scopolamine hydrobromide was performed four times a day for 10 days. The efficacy of various concentrations of CVMs (seven experimental groups) was first evaluated, and then 2% CVM was compared with commercial drugs, such as cyclosporine A (CsA), diquafosol (DQS), and rebamipide (REB) (seven experimental groups). The clinical changes, including tear production, corneal irregularity, and fluorescein staining, were measured after the instillation of various concentrations of CVMs and commercial drugs for 0, 3, 5, 7, and 10 days. Histological changes, such as corneal detachment, conjunctival goblet cell and mucin density staining, were assessed by staining the cornea or conjunctiva with hematoxylin-eosin, periodic acid-Schiff, and alcian blue. The expression of inflammatory markers and mucin factors was detected by immunohistochemistry and immunofluorescence in the lacrimal gland, cornea, and conjunctiva. Tear production was significantly increased in the 2% CVM group and was similar to that in the DQS and REB groups (P < 0.05). The corneal smoothness and fluorescein staining score were significantly improved in the 2% CVM group and were similar to those in the REB group (P < 0.05). Corneal epithelial cells were significantly decreased in the 2% CVM group, with similar observations made in the DQS and REB groups (P < 0.05). The conjunctival goblet cells and mucin density recovered in the 2% CVM group were similar to those in the CsA and REB groups (P < 0.05). The 2% CVM group showed suppressed expression of inflammatory factors in the lacrimal gland and was comparable to that seen in the CsA and REB groups. The expression of mucin factors was upregulated in the cornea and conjunctiva of the 2% CVM group and was similar to that of the CsA and REB groups. In conclusion, administration of CVM resulted in recovery or clinical and histological improvement of the murine dry eye model, and all the observed parameters were comparable to those with commercial drugs.

Effect of stem cells and fibrin concentration on the vascularization of the Medpor orbital implant.

BACKGROUND: To determine the effect of adipose-derived adult stem cells (ADASCs) and optimal concentration of fibrin on fibrovascular ingrowth into porous polyethylene orbital implants (Medpor). METHODS: Medpor sheet treated with O.25% fibrin only and ADASCs in mixtures containing fibrin (0.25%, 0.5% or 1.25%) were applied to a Medpor sheet and implanted in the back of each of 20 athymic nude mice. After 10 days, implants were removed and observed for fibrovascularization and stability. Haemoglobin, collagen and cellular DNA content were determined in quantitative assays. RESULTS: Haemoglobin, collagen and cellular DNA levels were significantly higher in ADASC group than in the cell-free implant (0.25% fibrin only) group (P < 0.01). The level of haemoglobin and collagen content was significantly higher in the ADASC + 0.5% fibrin group among the ADASC and fibrin mixtures (P < 0.01). CONCLUSION: ADASCs significantly improved fibrovascularization on Medpor compared with implants alone. Fibrin, used together with ADASCs to potentiate fibrovascularization, was most effective at concentrations of 0.5%.

Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides.

Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.

A New Ophthalmic Pharmaceutical Formulation, Topical Sulglycotide, Enhances the Ocular Mucin Secretion in Desiccation Stress-Mediated Dry Eye Disease.

Purpose: The aim of this study was the investigation of the effect of sulglycotide (SOS), a polysulfated glycopeptide derived from porcine duodenal mucin, for the treatment of dry eye disease. Methods: NOD.B10.H2b mice were exposed to an air draft for 10 days, and, simultaneously, scopolamine hydrobromide was injected subcutaneously. The mice were randomly divided into nine groups as follows: four kinds of SOS formulations and three kinds of commercial medicine. After 10 days of treatment, we estimated the effect of treatment on tear production, epithelium stabilization, mucin secretion, and inflammation. Results: The desiccation stress significantly decreased tear production and corneal epithelium stabilization, as well as markedly decreased the numbers of goblet cells and mucin-stained cells in conjunctiva. However, the topical 4% SOS eye drops markedly increased tear production and corneal stabilization, which recovered to baseline levels. In addition, topical 4% SOS significantly induced an increase in the numbers of goblet cells and the expression of membrane-associated mucins including MUC1, MUC4, and MUC16, as well as the gel-forming mucin, MUC5AC. Furthermore, SOS formulations provided anti-inflammatory improvement in a dose-dependent manner. Conclusions: In summary, we suggest that a new ophthalmic pharmaceutical formulation, topical sulglycotide, enhances the ocular mucin secretion in dry eye disease and can be used as a new ophthalmic pharmaceutical material to treat dry eye disease.

Potential Albumin-Based Antioxidant Nanoformulations for Ocular Protection against Oxidative Stress.

Amongst various drug administration methods, ophthalmic drug delivery has been a useful way for the treatment of eye-related diseases. However, therapeutic efficacy of ocular therapy for anterior or posterior eye segments through topical administration is considerably challenged by the number of anatomical and physiological barriers in the eyes affecting ocular bioavailability. In this respect, advanced biocompatible nanoformulations make it possible to improve drug delivery to the target sites and enhance ocular bioavailability of ophthalmic medicines. Various ocular diseases have been reported to be related to oxidative stresses in tissues, and polyphenolic compounds have been known for their antioxidant activities in various tissues, including the eyes. Despite drug efficacy, poor water solubility and intrinsic color of the compounds limit the drug's inclusion into the development of ocular medicine. In the present study, we investigated the antioxidant protectant efficacy of rosmarinic or ursolic acid in the retinal epithelial cells, as compared to those of curcumin, by forming nanospheres with bovine serum albumin. Our results demonstrate that antioxidant-containing nanoformulations provide a significantly higher drug solubility and decreased ROS (reactive oxygen species) production in the retinal epithelial cells. Finally, we also found that albumin-based nanoformulations could improve bioavailability and increase antioxidant activity of rosmarinic or ursolic acid in the retina to be applied as efficient ocular protectant.

Catechin solubilization by spontaneous hydrogen bonding with poly(ethylene glycol) for dry eye therapeutics.

Catechin exhibits various pharmacological effects, yet its poor aqueous solubility limits its clinical use. Here, we investigate a facile catechin solubilization method via spontaneous hydrogen bonding between catechin and poly(ethylene glycol) (PEG). The method is extremely simple in that mixing PEG with catechin followed by lyophilization completely converts insoluble catechin to soluble PEG/catechin nanoscale complexes. This solubilized catechin formulation is useful for preparing eyedrop medicine, and we demonstrate that the solubilized catechin exhibits therapeutic effect upon dry eye diseases.

Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery.

Ocular drug delivery has been a well-known route for the drug administration for the treatment of ocular diseases. However, numerous anatomical and physiological barriers prevailing in the eye itself create considerable challenges for achieving the necessitated therapeutic efficacy along with ocular bioavailability. However, recent advances in nanoengineered strategies hold definite promises in terms of devising improved ophthalmic medicines for the effective drug delivery to target the sites with enhanced ocular bioavailability. Curcumin, a hydrophobic polyphenol yellow colored compound, and its metabolic reduced product, tetrahydrocurcumin (THC), have been known for their beneficial pharmacological functions, such as anti-inflammatory or anti-oxidant activities at various tissue sites. However, the low aqueous solubility of these compounds results in their poor bioavailability, thereby limiting their widespread application. Therefore, in the present study, we investigated the changes in drug solubility by forming inclusion complexes with different derivatives of hydroxypropyl (HP)-cyclodextrins (CD). To this end, the spray drying technique was used for nanoengineering curcumin or THC-loaded formulations to improve the stability of formulations during the storage. The formulations were characterized in terms of physicochemical properties and cellular permeability. The results demonstrated that the encapsulation of curcumin (or THC) into the HP-CDs significantly increased the drug solubility and enhanced the corneal and retinal epithelial permeability. Curcumin or THC complexes in HP-CDs with improved bioavailability also induced anti-oxidant activity (SOD1, CAT1, and HMOX1) in higher levels in the ocular epithelial cells and showed oxidative protection effects in rabbit cornea tissues that will boost up their application in ocular medicine.

Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration.

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.

Inhibition of proliferation in colon cancer cell lines and harmful enzyme activity of colon bacteria by Bifidobacterium adolescentis SPM0212.

In this study, we assessed the anticancer activity and bacterial enzyme inhibition of Bifidobacterium adolescentis SPM0212. B. adolescentis SPM0212 inhibited the proliferation of three human colon cancer cell lines: HT-29, SW 480, and Caco-2. SPM0212 also dose-dependently inhibited TNF-á production and changes in cellular morphology. B. adolescentis SPM0212 inhibited harmful fecal enzymes, including â-glucuronidase, â-glucosidase, tryptophanase, and urease. Thus, B. adolescentis SPM0212 exerts an anticancer effect and inhibits harmful fecal enzymes.