Development of an implantable collamer lens sizing model: a retrospective study using ANTERION swept-source optical coherence tomography and a literature review.

BACKGROUND: Optimal sizing for phakic intraocular lens (EVO-ICL with KS-AquaPort) implantation plays an important role in preventing postoperative complications. We aimed to formulate optimal lens sizing using ocular biometric parameters measured with a Heidelberg anterior segment optical coherence tomography (AS-OCT) device. METHODS: We retrospectively analyzed 892 eyes of 471 healthy subjects treated with an intraocular collamer lens (ICL) and assigned them to either the development (80%) or validation (20%) set. We built vault prediction models using the development set via classic linear regression methods as well as partial least squares and least absolute shrinkage and selection operator (LASSO) regression techniques. We evaluated prediction abilities based on the Bayesian information criterion (BIC) to select the best prediction model. The performance was measured using Pearson's correlation coefficient and the mean squared error (MAE) between the achieved and predicted results. RESULTS: Measurements of aqueous depth (AQD), anterior chamber volume, anterior chamber angle (ACA) distance, spur-to-spur distance, crystalline lens thickness (LT), and white-to-white distance from ANTERION were highly associated with the ICL vault. The LASSO model using the AQD, ACA distance, and LT showed the best BIC results for postoperative ICL vault prediction. In the validation dataset, the LASSO model showed the strongest correlation (r = 0.582, P < 0.001) and the lowest MAE (104.7 µm). CONCLUSION: This is the first study to develop a postoperative ICL vault prediction and lens-sizing model based on the ANTERION. As the measurements from ANTERION and other AS-OCT devices are not interchangeable, ANTERION may be used for optimal ICL sizing using our formula. Because our model was developed based on the East Asian population, further studies are needed to explore the role of this prediction model in different populations.

Predicting Postoperative Anterior Chamber Angle for Phakic Intraocular Lens Implantation Using Preoperative Anterior Segment Metrics.

Purpose: The anterior chamber angle (ACA) is a critical factor in posterior chamber phakic intraocular lens (EVO Implantable Collamer Lens [ICL]) implantation. Herein, we predicted postoperative ACAs to select the optimal ICL size to reduce narrow ACA-related complications. Methods: Regression models were constructed using pre-operative anterior segment optical coherence tomography metrics to predict postoperative ACAs, including trabecular-iris angles (TIAs) and scleral-spur angles (SSAs) at 500 µm and 750 µm from the scleral spur (TIA500, TIA750, SSA500, and SSA750). Data from three expert surgeons were assigned to the development (N = 430 eyes) and internal validation (N = 108 eyes) datasets. Additionally, data from a novice surgeon (N = 42 eyes) were used for external validation. Results: Postoperative ACAs were highly predictable using the machine-learning (ML) technique (extreme gradient boosting regression [XGBoost]), with mean absolute errors (MAEs) of 4.42 degrees, 3.77 degrees, 5.25 degrees, and 4.30 degrees for TIA500, TIA750, SSA500, and SSA750, respectively, in internal validation. External validation also showed MAEs of 3.93 degrees, 3.86 degrees, 5.02 degrees, and 4.74 degrees for TIA500, TIA750, SSA500, and SSA750, respectively. Linear regression using the pre-operative anterior chamber depth, anterior chamber width, crystalline lens rise, TIA, and ICL size also exhibited good performance, with no significant difference compared with XGBoost in the validation sets. Conclusions: We developed linear regression and ML models to predict postoperative ACAs for ICL surgery anterior segment metrics. These will prevent surgeons from overlooking the risks associated with the narrowing of the ACA. Translational Relevance: Using the proposed algorithms, surgeons can consider the postoperative ACAs to increase surgical accuracy and safety.

Indigo Pulverata Levis (Chung-Dae, Persicaria tinctoria) Alleviates Atopic Dermatitis-like Inflammatory Responses In Vivo and In Vitro.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with a type 2 T helper cell (Th2) immune response. The IndigoPulverata Levis extract (CHD) is used in traditional Southeast Asian medicine; however, its beneficial effects on AD remain uninvestigated. Therefore, we investigated the therapeutic effects of CHD in 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mice and tumor necrosis factor (TNF)-α- and interferon gamma (IFN)-γ-stimulated HaCaT cells. We evaluated immune cell infiltration, skin thickness, and the serum IgE and TNF-α levels in DNCB-induced AD mice. Moreover, we measured the expression levels of pro-inflammatory cytokines, mitogen-activated protein kinase (MAPK), and the nuclear factor-kappa B (NF-κB) in the mice dorsal skin. We also studied the effect of CHD on the translocation of NF-κB p65 and inflammatory chemokines in HaCaT cells. Our in vivo results revealed that CHD reduced the dermis and epidermis thicknesses and inhibited immune cell infiltration. Furthermore, it suppressed the proinflammatory cytokine expression and MAPK and NF-κB phosphorylations in the skin tissue and decreased serum IgE and TNF-α levels. In vitro results indicated that CHD downregulated inflammatory chemokines and blocked NF-κB p65 translocation. Thus, we deduced that CHD is a potential drug candidate for AD treatment.

Improved Biological Responses of Titanium Coating Using Laser-Aided Direct Metal Fabrication on SUS316L Stainless Steel.

Direct metal fabrication (DMF) coatings have the advantage of a more uniform porous structure and superior mechanical properties compared to coatings provided by other methods. We applied pure titanium metal powders to SUS316L stainless steel using laser-aided DMF coating technology with 3D printing. The purpose of this study was to determine the efficacy of this surface modification of stainless steel. The capacity of cells to adhere to DMF-coated SUS316L stainless steel was compared with machined SUS316L stainless steel in vitro and in vivo. Morphological in vitro response to human osteoblast cell lines was evaluated using scanning electron microscopy. Separate specimens were inserted into the medulla of distal femurs of rabbits for in vivo study. The distal femurs were harvested after 3 months, and were then subjected to push-out test and histomorphometrical analyses. The DMF group exhibited a distinct surface chemical composition, showing higher peaks of titanium compared to the machined stainless steel. The surface of the DMF group had a more distinct porous structure, which showed more extensive coverage with lamellipodia from osteoblasts than the machined surface. In the in vivo test, the DMF group showed better results than the machined group in the push-out test (3.39 vs. 1.35 MPa, respectively, p = 0.001). In the histomorphometric analyses, the mean bone-to-implant contact percentage of the DMF group was about 1.5 times greater than that of the machined group (65.4 ± 7.1% vs. 41.9 ± 5.6%, respectively; p < 0.001). The porous titanium coating on SUS316L stainless steel produced using DMF with 3D printing showed better surface characteristics and biomechanical properties than the machined SUS316L.

Sequential biowashing-biopile processes for remediation of crude oil contaminated soil in Kuwait.

The application of biological processes for remediation of the aged crude oil-contaminated soil of Kuwait can be an inefficient way, thus, this study developed 20 d-sequential biowashing and biopile processes where the biowashing step uses an enrichment culture of the indigenous soil bacterial community and the biopile step includes hemoglobin-catalyzed oxidation (HCO). The residual total petroleum hydrocarbons (TPH) concentrations and CO2 generation were measured to determine the removal efficiency, and the bacterial community changes were studied to investigate the effect of the sequential processes on the soil indigenous bacterial community. The enrichment culture grown on hemoglobin showed an increased surface activity, and this promoted desorption and emulsification of crude oil from the soil sample in the biowashing step resulting in 75% TPH removal. Potential surfactant-producing bacterial species were observed in the soil sample after biowashing. The HCO in the beginning of the biopile step removed 21% of the residual TPH, and further TPH removal was observed with a longer biopile period. Overall, the sequential biowashing and biopile processes removed 86% TPH. The results show that the developed sequential biowashing and biopile processes can be used to efficiently remediate the aged crude oil-contaminated soil of Kuwait.

DNA Topoisomerase Inhibitory Activity of Constituents from the Flowers of Inula japonica.

Fourteen compounds were isolated from the flowers of Inula japonica THUNB. (Asteraceae), including two new compounds, (1S,2S,4S,5S,8S,10R)-2-acetoxy-4,3-dihydroxy-pseudoguai-7(11)-en-12,8-olide (1) and (1S,2S,4S,5S,8S,10R)-2,4,13-trihydroxy-pseudoguai-7(11)-en-12,8-olide (2), and twelve known compounds, budlein B (3), 6ß-hydroxytomentosin (4), 6-deacetoxybritanin (5), 4-epipulchellin (6), britanin (7), tomentosin (8), (+)-dihydroquercetin (9), (-)-syringaresinol (10), quercetagetin 3,4'-dimethyl ether (11), luteolin (12), britanin G (13) and inuchinenolide C (14). Structures of 1 and 2 were determined based on one and two dimensional (1D)- and (2D)-NMR data and Mosher's esterification method. Compounds 9 and 12 showed inhibitory activities toward DNA topoisomerase I with IC50 values of 55.7 and 37.0 µM, respectively, compared to camptothecin (CPT) with an IC50 of 24.5 µM. Compounds 7-9 and 11-14 exhibited more potent inhibitory activity against topoisomerases II with IC50 values of 6.9, 3.8, 3.0, 6.9, 10.0, 14.7 and 13.8 µM, respectively, than that of etoposide (VP-16) with an IC50 of 26.9 µM. Compounds 4-7 and 10-14 exhibited weak cytotoxicities to the selected cancer cell lines.

meso-Dihydroguaiaretic acid attenuates airway inflammation and mucus hypersecretion in an ovalbumin-induced murine model of asthma.

meso-Dihydroguaiaretic acid (MDGA), which is a dibenzylbutane lignin isolated from the ethyl acetate fraction of Saururus chinensis, has various biological activities, including anti-oxidative, anti-inflammatory, anti-bacterial, and neuroprotective effects. However, no report has examined the potential anti-asthmatic activity of MDGA. In this study, we evaluated the protective effects of MDGA on asthmatic responses, particularly airway inflammation and mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. Intragastric administration of MDGA significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, tumor necrosis-α (TNF-α), eotaxin, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that MDGA inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. Moreover, MDGA markedly attenuated the OVA-induced activations of nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinases 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Together, these results suggest that MDGA effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of T helper 2 (Th2) cytokines, chemokines, and adhesion molecules, and inhibiting the activations of NF-κB and MAPKs.

Protective Effects of Manassantin A against Ethanol-Induced Gastric Injury in Rats.

Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

Quality evaluation of Carthami Flos by HPLC-UV.

A HPLC-DAD method was developed for simultaneous determination of four marker compounds, kaempferol-3-O-rutinoside, safflomin A, safflomin B and bidenoside C, in the extract of the flowers of Carthamus tinctorius Linne. Natural samples were extracted in 50% aqueous methanol by ultra-sonication for 60 min. Marker compounds were separated on a C18 column by two-step gradient elution of mobile phase (acetonitrile/water) at a flow rate of 0.75 mL/min and detected at 210 nm. The retention times of safflomin A and safflomin B were shifted according to the pH of the mobile phase. The optimized analytical method was validated to confirm linearity, precision, accuracy and stability of marker compounds. The method was successfully employed to analyze 17 natural samples from different regions, and the data matrix was monitored and visualized by principal component analysis. The assay method could be applied for quality control of the flowers of C. tinctorius Linne.

Inducing rigid local structure around the zinc-binding region by hydrophobic interactions enhances the homotrimerization and apoptotic activity of zinc-free TRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), existing as homotrimer in solution, contains a unique zinc-binding site coordinated by three Cys230 residues at the tip of trimeric interface. TRAIL mutant with replacements of Cys230 with Ala (TRAIL(C230A)) negligibly formed trimeric structure and showed no apoptotic activity. Here, to elucidate the relationship between the trimeric stability and the apoptotic activity of TRAIL(C230A), we rationally designed mutations to induce homotrimerization of TRAIL(C230A) by substituting for the three residues involved in hydrogen bonding (Tyr183 and Tyr243) and putative repulsive electrostatic (Arg227) interactions at the buried trimeric interface into hydrophobic residues, like Y183F, Y243F, and R227I. The TRAIL(C230A)-derived mutants exhibited enhanced homotrimerization, but only the mutants containing R227I exhibited significant apoptosis-inducing activity in cancer cells. These results, together with the induction of rigid local structure around the zinc-binding region by R227I in TRAIL(C230A), suggest that ordered, rigid structure around the zinc-binding region is critical for the homotrimerization and apoptotic activity of TRAIL.

A human scFv antibody against TRAIL receptor 2 induces autophagic cell death in both TRAIL-sensitive and TRAIL-resistant cancer cells.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death in a variety of tumor cells without significant cytotoxicity on normal cells. However, many cancer cells with apoptotic defects are resistant to treatment with TRAIL alone, limiting its potential as an anticancer therapeutic. Here, we report on the tumoricidal activity of a human single-chain fragment variable, HW1, which specifically binds to TRAIL receptor 2 (TR2) without competing with TRAIL for the binding. HW1 treatment as a single agent induces autophagic cell death in a variety of both TRAIL-sensitive and TRAIL-resistant cancer cells, but exhibits much less cytotoxicity on normal cells. The HW1-induced autophagic cell death was inhibited by an autophagy inhibitor, 3-methyladenine, or by RNA interference knockdown of Beclin-1 and Atg7. We also show that the HW1-mediated autophagic cell death occurs predominantly via the c-Jun NH(2)-terminal kinase pathway in a caspase-independent manner. Analysis of the death-inducing signaling complex induced by HW1 binding to TR2 exhibits the recruitment of TNF receptor-associated death domain and TNF receptor-associated factor 2, but not Fas-associated death domain, caspase-8, or receptor-interacting protein, which is distinct from that induced by TRAIL. Our results reveal a novel TR2-mediated signaling pathway triggering autophagic cell death and provides a new strategy for the elimination of cancer cells, including TRAIL-resistant tumors, through nonapoptotic cell death.