Salmonellosis outbreaks linked to eggs at 2 gimbap restaurants in the Republic of Korea.

Objectives: Salmonellosis outbreaks occurred at 2 restaurants 2 days apart, and an epidemiological investigation was conducted to determine whether the outbreaks were connected. Methods: Case studies were conducted for both outbreaks. Stool samples were collected from individuals, and food samples were collected from the restaurants. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing analyses were performed on outbreak-related Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) isolates. Traceback investigations were also conducted for the ingredients from gimbap restaurants A and B. Results: In total, 106 people from gimbap restaurant A and 5 from gimbap restaurant B met the case definition. Salmonella Enteritidis was detected in samples from 2 food handlers, 22 patients, and 1 food (iceberg lettuce) at gimbap restaurant A and from 1 patient at gimbap restaurant B. According to PFGE, all isolates were identified as SEGX01.089. The molecular typing of all isolates showed the same pattern, and the genetic distance was close according to phylogenetic analysis. Eggs were the only food ingredient that was supplied to both gimbap restaurants. Conclusion: The outbreaks were caused by Salmonella Enteritidis, and the source of infections was suspected to be contaminated eggs. To prevent foodborne outbreaks of Salmonella, restaurants should heat eggs sufficiently, and egg farms need to establish management systems that prevent Salmonella infections.

Model Informed Development of SIM0295 in Patients with Gout and Hyperuricemia and Healthy Volunteers Using a Population Pharmacokinetics/ Pharmacodynamics Approach.

BACKGROUND: SIM0295, a novel inhibitor of human uric acid transporter 1 (hURAT1), is used to treat patients with gout and hyperuricemia. This study aimed to develop population pharmacokinetics and pharmacodynamics (popPK/PD) models of SIM0295 and explore potential covariates to inform clinical drug development. RESEARCH DESIGN AND METHODS: Data were obtained from four phase I studies conducted in healthy Korean and Chinese subjects and two phase II studies conducted in Korean patients with gout and hyperuricemia. The popPK/PD model of SIM0295 was developed using nonlinear mixed effects modeling. RESULTS: SIM0295 pharmacokinetics was described using a two-compartment model with the absorption of four transit compartments and first-order elimination. PK parameters were normalized to weight via allometric scaling. Food was identified as a factor significantly affecting the absorption rate, with no clinical relevance. The sigmoid Emax model with a semi-mechanism of inhibition of serum uric acid (sUA) reabsorption was used to describe the exposure-response relationship. Additionally, Monte Carlo simulations demonstrated that approimately 9 mg/day of SIM0295 for 7 days could achieve the maximum decrease in sUA. CONCLUSION: The established popPK/PD model characterized the dose-exposure-response relationship for SIM0295 in healthy subjects and patients with gout and hyperuricemia and could be used to inform the drug development.

Status of the Newborn Hearing Screening in the 4-Months Age National Infant Health Checkup in Korea: A Nationwide Population-Based Study.

BACKGROUND: The aims of this study are to review data on 4-months age National Health Screening Program for Infants and Children (NHSPIC) using a National Health Insurance Service (NHIS) database, and to analyze the newborn hearing screening (NHS) results and related characteristics of the 4-months NHSPIC for 7 years in South Korea. METHODS: We analyzed a NHIS database of infants who had participated in the 4-month age NHSPIC from 2010 to 2016. According to the results of hearing questionnaires and physical examination, we analyzed the outcomes of NHS and related infantile and socioeconomic factors. RESULTS: Among 3,128,924 of total eligible infants in Korea between the year 2010 and 2016, 69.2% (2,164,621 infants) conducted 4-months age NHSPIC, and 94.4% (2,042,577 infants) of which performed hearing questionnaires regarding NHS. Among the total hearing examinees, premature infants accounted for 3.6%, infants who were hospitalized in the neonatal intensive care unit (NICU) for more than 5 days accounted for 5.6%, and infants with head and neck abnormalities were 0.6%. The NHS performing rate was 79.1% for total hearing examinees in 2010, but gradually increased to 88.9% in 2016. The NHS performing rate in 2016 was 93.4% for premature infants, 91.7% for NICU hospitalized babies. The mean referral rate was 0.6% for total hearing examinees, 1.4% for premature infants, and 2.3% for NICU hospitalized babies. When we analyzed the NHS performing rate and the referral rate according to the household income level, the NHS performing rate of infants in Medical Aid programs was the lowest as 65.6%, and the NHS performing rates in other five levels of NHIS was higher ranging between 85.1% to 86.0%. The referral rate of infants in the Medical Aid program (3.8%) was significantly higher than those of infants in other classes (1.10-1.25%). CONCLUSION: The estimated overall NHS performing rate in Korea gradually increased and was 88.9% in 2016. The overall referral rate was low as 0.6%, and it was significantly different depending on the infant's health condition and household income levels. We assume that our finding would help to establish policies managing hearing impaired children, and to develop the customized hearing care service programs considering the household economic levels.

Evaluation of a Rapid and Simple Method for Assessing Retinal Vessel Structures in Adult Zebrafish.

The evaluation of retinal vascular structures is important for analyzing various ophthalmic diseases. Conventional trypsin digestion was used for separating retinal vasculatures in mouse, rat, and other animal models; however, the trypsin method alone is technically difficult to perform and has not been reported in zebrafish to date. In this study, we introduced a rapid and convenient method that allows the investigation of fine vessel structures at a cellular level in the relatively intact retinal vasculature of adult zebrafish. Using an anti-ZO-1 antibody, tight junction structures in retinal vessels were examined in detail and several different cell types constituting blood vessels in arterial and capillary areas were identified. In addition, using cell type-specific antibodies, we identified smooth muscle cells, blood cells, and endothelial cells in the retinal vasculature. Finally, using the hyperglycemic model, we observed the dilation of retinal vessels, the downregulation of tight junction proteins, and the reduction in smooth muscle cells. Based on these results, we provide a rapid and convenient method for the study of retinal vasculature disease in the zebrafish animal model.

dTMP imbalance through thymidylate 5'-phosphohydrolase activity induces apoptosis in triple-negative breast cancers.

Immunotherapy has a number of advantages over traditional anti-tumor therapy but can cause severe adverse reactions due to an overactive immune system. In contrast, a novel metabolic treatment approach can induce metabolic vulnerability through multiple cancer cell targets. Here, we show a therapeutic effect by inducing nucleotide imbalance and apoptosis in triple negative breast cancer cells (TNBC), by treating with cytosolic thymidylate 5'-phosphohydrolase (CT). We show that a sustained consumption of dTMP by CT could induce dNTP imbalance, leading to apoptosis as tricarboxylic acid cycle intermediates were depleted to mitigate this imbalance. These cytotoxic effects appeared to be different, depending on substrate specificity of the 5' nucleotide or metabolic dependency of the cancer cell lines. Using representative TNBC cell lines, we reveal how the TNBC cells were affected by CT-transfection through extracellular acidification rate (ECAR)/oxygen consumption rate (OCR) analysis and differential transcription/expression levels. We suggest a novel approach for treating refractory TNBC by an mRNA drug that can exploit metabolic dependencies to exacerbate cell metabolic vulnerability.

[The Development of a Tool for Assessment of Spiritual Distress in Cancer Patients].

PURPOSE: This study was conducted to develop a scale to measure spiritual distress in cancer patients. METHODS: A total of 69 preliminary items for the spiritual distress assessment tool (SDAT) were compiled, based on a literature review, selection of empirically relevant items through concept analysis of hybrid models, confirmation of content validity by experts, cognitive interviews, and a pretest. Self-administered questionnaires were collected between April 1 and July 31, 2018, from 225 cancer patients at four medical institutions and one nursing home. The data were analyzed using item analysis, exploratory factor analysis, convergent and discriminant validity, and Pearson correlation for criterion validity. Reliability was tested by Cronbash's α coefficient. RESULTS: The final version of the SDAT consisted of 20 items. Five-factors, loss of peace, burden of family, avoidance of confronting death, guilt and remorse, regret for not being able to apololgize and forgive were extracted, and showed 62.8% of total variance. The factors were confirmed through convergent and discriminant validity. Criterion validity was confirmed by functional assessment chronic illness therapy spiritual well-being scale 12 (FACIT-Sp12). The overall Cronbach's α was .91, and the coefficients of each subscale ranged from .78~.83. CONCLUSION: The SDAT for cancer patients is valid and reliable. It is suggested that the tool can be used to measure spiritual distress in cancer patients.

Extract of Moutan radicis cortex and Cinnamomi ramulus ameliorates laser-induced choroidal neovascularization in Brown-Norway rats.

BACKGROUND: Moutan radicis cortex (MRC) and Cinnamomi ramulus (CR) are commonly used in eastern Asian traditional medicine to treat various diseases including cerebrovascular and cardiovascular, and have wide spectrum of pharmacological activities. However, the effect against laser-induced choroidal neovascularization (CNV) of extract of MRC and CR (1:1) (MRCCR) has not yet been studied. PURPOSE: Our aim was to investigate the inhibitory effect of MRCCR on pathological CNV in laser-treated Brown-Norway (BN) rats. METHODS: MRCCR (60, 90 mg/kg) was orally administered twice per day for 15 days from the day of CNV formation in laser-treated BN rats. Effects of MRCCR or its constituents on cell migration, tube formation, hyperpermeability and phosphorylation of FAK/p38 MAPK were confirmed in humane retinal microvascular endothelial cells or human retinal pigment epithelial cells. RESULTS: MRCCR significantly reduced the CNV lesions areas and the extent of fluorescein leakage. MRCCR and its constituents such as ellagic acid, paeonol or gallic acid decreased cell migration, tube formation or hyperpermeability. MRCCR inhibited the phosphorylation of FAK and p38 MAPK. CONCLUSION: Combining the oral MRCCR and intravitreal injection of anti-VEGF medicine may result in a more potent therapeutic effect and consequently bring the reduction in eye injection numbers for patients with wet AMD.

POCU1b, the n-Butanol Soluble Fraction of Polygoni Cuspidati Rhizoma et Radix, Attenuates Obesity, Non-Alcoholic Fatty Liver, and Insulin Resistance via Inhibitions of Pancreatic Lipase, cAMP-Dependent PDE Activity, AMPK Activation, and SOCS-3 Suppression.

This study investigated the effects of the n-BuOH soluble fraction of Polygoni Cuspidati 80% ethanol extract (POCU1b) on high-fat diet (HFD)-induced obesity, non-alcoholic fatty liver (NAFL), and insulin resistance (IR) to find a safe and more effective agent. HPLC profiling of POCU1b identified seven marker compounds. POCU1b increased glycerol release, cyclic adenosine monophosphate (cAMP) level, and inhibited phosphodiesterase (PDE) activity. Seven weeks of POCU1b treatment decreased body weight gain, weight and adipocyte size in fat tissues, serum lipids, and triglyceride and lipid droplets in the livers of HFD-fed rats. POCU1b improved blood glucose, insulin sensitivity, and impaired insulin secretion in the pancreas. Further, POCU1b ameliorated adiponectin, leptin, IL-6 and TNF-α levels, increased AMPK and p-ACC expression, activated CPT-1 activity, and suppressed FAS mRNA, SOCS-3 protein expression, and NF-κB DNA-binding activity. When compared with the Xenical®-treated group, a positive group, the action of POCU1b on body weight was more effective than that of Xenical. POCU1b did not show side effects, such as oily spotting and loss of appetite. These results suggest that POCU1b possesses therapeutic or preventive potential for obesity, NAFL and IR via inhibitions of pancreatic lipase and cAMP-dependent PDE activity, AMPK activation, and SOCS-3 suppression, without oily spotting and loss of appetite.

Status of early hearing detection and intervention in South Korea: a nationwide population-based study of national infant health checkup.

The aim of this study was to evaluate the status of early hearing detection and intervention after newborn hearing screening (NHS) in South Korea. A retrospective review of Korean national health insurance service data of all infants receiving the 4-month old national infant health checkup between 2010 and 2016 from a nationwide population-based database was conducted. Based on the results of the NHS-administered hearing questionnaires as part of the national infant health checkup, individuals were classified into "pass" (1,730,615 infants) or "refer" (10,941 infants) groups. Next, an analysis was conducted of age and the frequencies of tracking audiologic tests and surgeries of the middle ear (ME) and cochlear implants (CI). Diagnostic auditory brainstem response and audiometry, and surgeries of ME and CI were significantly performed more and earlier in the refer group compared with the pass group. For infants in the pass group who were presumed to have delayed or acquired hearing loss, the time of the first audiology tests and CI surgery was significantly delayed compared to those in the refer group; the average ages for first CI were 37 and 52 months in the refer group and pass group, respectively. Therefore, for early detection of delayed-onset hearing loss, regular hearing screening programs should be considered throughout the preschool ages.

Synthesis and Cytotoxicity Studies of Bioactive Benzofurans from Lavandula agustifolia and Modified Synthesis of Ailanthoidol, Homoegonol, and Egonol.

2-Aryl/alkylbenzofurans, which constitute an important subclass of naturally occurring lignans and neolignans, have attracted extensive synthetic efforts due to their useful biological activities and significant pharmacological potential. Herein, we report a general and efficient approach to divergent 2-arylbenzofurans through a one-pot synthesis of versatile 2-bromobenzofurans as key intermediates. Using this approach, the first total synthesis of a series of trisubstituted and tetrasubstituted benzofurans bearing the hydroxyethyl unit, including the natural compounds isolated from Lavandula agustifolia (1-3) and their non-natural derivatives (4-8), was accomplished. We also report a modified synthesis of ailanthoidol, homoegonol, and egonol that enables the divergent synthesis of their derivatives for future exploration. Among these, the representative phenolic natural compound 2 and its derivatives 7 and 5 induced apoptotic cell death related poly(ADP-ribose) polymerase (PARP) cleavage in MCF74, A549, PC3, HepG2, and Hep3B cancer cell lines. Additionally, the tumor suppressor protein p53 was also induced in p53 wild type cancer cells.

The Herbal Combination CPA4-1 Inhibits Changes in Retinal Capillaries and Reduction of Retinal Occludin in db/db Mice.

Increased formation of advanced glycation end products (AGEs) plays an important role in the development of diabetic retinopathy (DR) via blood-retinal barrier (BRB) dysfunction, and reduction of AGEs has been suggested as a therapeutic target for DR. In this study, we examined whether CPA4-1, a herbal combination of Cinnamomi Ramulus and Paeoniae Radix, inhibits AGE formation. CPA4-1 and fenofibrate were tested to ameliorate changes in retinal capillaries and retinal occludin expression in db/db mice, a mouse model of obesity-induced type 2 diabetes. CPA4-1 (100 mg/kg) or fenofibrate (100 mg/kg) were orally administered once a day for 12 weeks. CPA4-1 (the half maximal inhibitory concentration, IC50 = 6.84 ± 0.08 µg/mL) showed approximately 11.44-fold higher inhibitory effect on AGE formation than that of aminoguanidine (AG, the inhibitor of AGEs, IC50 = 78.28 ± 4.24 µg/mL), as well as breaking effect on AGE-bovine serum albumin crosslinking with collagen (IC50 = 1.30 ± 0.37 µg/mL). CPA4-1 treatment ameliorated BRB leakage and tended to increase retinal occludin expression in db/db mice. CPA4-1 or fenofibrate treatment significantly reduced retinal acellular capillary formation in db/db mice. These findings suggested the potential of CPA4-1 as a therapeutic supplement for protection against retinal vascular permeability diseases.

Osteomeles schwerinae Extract and Its Major Compounds Inhibit Methylglyoxal-Induced Apoptosis in Human Retinal Pigment Epithelial Cells.

The accumulation and formation of advanced glycation end products (AGEs) are related to diabetes and age-related disease. Osteomeles schwerinae C. K. Schneid. (Rosaceae, OSSC) is used traditionally for the treatment of various diseases in Asia. Previous studies have shown that OSSC elicits preventive effects in an in vivo model of diabetes. This study was to evaluate the antiapoptotic effects of dried leaves and twigs of OSSC extract and its major compounds in ARPE-19 cells-spontaneously arising human retinal pigment epithelial cells-under diabetic conditions. To examine the effects of an OSSC extract and its active compounds (acetylvitexin, hyperoside and quercitrin) on apoptosis in methylglyoxal (MG, the active precursor in the formation of AGEs)-treated ARPE-19 cells and the mechanism by which these effects occur, apoptosis was measured using flow cytometry analysis. Protein expression levels of phospho-p53 (p-p53), Bax and Bcl-2 were determined by western blot analyses. The OSSC extract inhibited apoptosis in MG-treated ARPE-19 cells in a dose-dependent manner. The major compounds also reduced the rate of apoptosis. Both the extract and major compounds also inhibited the expression of p-p53 and Bax and increased the levels of Bcl-2 that had been previously reduced by MG treatment. The OSSC extract (0.1 µg/mL) and its major compounds (0.01 µM) attenuated apoptosis in ARPE-19 cells under toxic diabetic conditions by downregulating of expression of p-p53 and Bax. OSSC may serve as an alternative therapy to retard the development of diabetic retinopathy.

[Development and Validation of the New Version of Spirituality Assessment Scale].

PURPOSE: The purpose of this study was to develop a new version of Spirituality Assessment Scale (N-SAS) and verify its reliability and validity. METHODS: The total of 59 preliminary items for the N-SAS were selected through a literature review, two rounds of experts' content validation, cognitive interviews, and pre-tests. Verification of its reliability and validity was divided into two phases. In Phase I, questionnaires were collected from 219 adults. Reliability was tested using Cronbach's alpha, validity with item analysis, and exploratory factor analysis. In Phase II, questionnaires developed based on the results of Phase I were collected from 225 adults. Reliability was tested using Cronbach's alpha, validity with confirmatory factor analysis, and criterion validity. RESULTS: The final version of the N-SAS comprised two dimensions (vertical and horizontal), four domains (relationship with God; meaning of life and self-integration; self-transcendence; and relationship with others, neighborhoods, and nature), and 44 items were identified. Total Cronbach's α was .97; those of each subscale ranged from .79 to .98. N-SAS scores were positively correlated with the scores of Howden's Spiritual Assessment Scale (r=.81, p<.001). CONCLUSION: Findings suggest that the N-SAS can be used to measure spirituality in adults. The use of N-SAS is expected to facilitate perceiving patient's spiritual needs and providing spiritual care.

Anti-angiogenic effect of EGHB010, a standardized herbal formula of Paeoniae radix and Glycyrrhizae radix.

EGHB010 is a standardized herbal formula of the rhizome mixture of Paeonia lactiflora Pallas and Glycyrrhiza uralensis Fisch. Neovascularization in the retina is a common pathophysiology of diabetic retinal microvasculopathy and exudative macular degeneration. In this study, we evaluated the inhibitory effects of EGHB010 on abnormal retinal angiogenesis in a hyperoxia-induced neovascular retinopathy model. Vascular endothelial growth factor (VEGF)-mediated vascular tube formation was assayed in human umbilical vascular endothelial cells (HUVECs). Experimental angiogenesis in the retinas was induced by exposing C57BL/6 pups to hyperoxic environment (75% oxygen) on postnatal day 7 (P7) and then returning them to normal oxygen pressure on P12. EGHB010 (50 and 100 mg/kg/day) was administered intraperitoneally for 5 days (P12 - P16). Retinal flat mounts were prepared to measure the extent of retinal neovascularization on P17. The incubation of HUVECs with EGHB010 (1-25 µg/mL) resulted in the inhibition of VEGF-mediated tube formation in a dose-dependent manner. EGHB010 at doses of 50 and 100 mg/kg/day inhibited the formation of retinal neovascular tufts by 31.15±2.28% and 59.83±2.92%, respectively. Together, our results indicate that EGHB010 is a potent anti-angiogenic agent and may have potential for the control of abnormal retinal vessel growth in patients with ischemic retinopathy.

Polydatin Inhibits NLRP3 Inflammasome in Dry Eye Disease by Attenuating Oxidative Stress and Inhibiting the NF-κB Pathway.

Polydatin (also named pieceid, (E)-piceid, (E)-polydatin, trans-polydatin, or 3,5,4'-trihydroxystilbene-3-b-D-glucoside) is a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae). A previous study showed that polydatin has antioxidant and anti-inflammatory effects. However, the effect of polydatin in dry eye disease (DED) has not been elucidated. DED rat models were induced by exorbital lacrimal gland-excision. In vivo, the present study showed that the excision of lacrimal glands induced changes such as reduced tear fluid, severe corneal irregularity, damage, tear film break, and goblet cell loss as well as increased inflammation cytokine and NLRP3 expression in conjunctival tissue. However, these changes were restored by polydatin eye dropping. In vitro, polydatin inhibited hyperosmolar stress-induced inflammation through attenuation of the translocation of NF-κB to the nucleus and the mRNA expression of TNF-α, IL-6, IL-1ß, and MMP9. In addition, the hyperosmolar stress-induced NLRP3 inflammasome pathway and ROS production were inhibited by polydatin. Our findings provided insight into the effect of polydatin as a candidate reagent for the treatment of DED.

Pueraria lobata Extract Protects Hydrogen Peroxide-Induced Human Retinal Pigment Epithelial Cells Death and Membrane Permeability.

BACKGROUND: Pueraria lobata is used in traditional Asian medicine to treat cardiovascular diseases, diarrhea, diabetes mellitus, and diabetic complications such as diabetic retinopathy. Oxidative stress in retinal pigment epithelial cells is implicated in the pathogenesis of retinopathy and age-related macular degeneration (AMD). Here, we evaluated whether the P. lobata extract can prevent cell death and decrease membrane permeability in oxidative stress-induced human retinal pigment epithelial cells. METHODS: The effects of P. lobata extract on hydrogen peroxide- (H2O2-) induced oxidative stress were investigated using 2',7'-dichlorofluorescin diacetate, western blotting, and immunohistochemistry in human retinal pigment epithelial cells. The effects of puerarin, daidzein, and daidzin isolated from P. lobata extract were also studied by determining cell death, reactive oxygen species (ROS) generation, and p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation. RESULTS: Our results showed that the P. lobata extract inhibited ROS generation, suppressed the disruption of zonula occludens-1 (ZO-1), and reduced membrane permeability in H2O2-induced human retinal pigment epithelial cells. Additionally, the P. lobata extract prevented the inhibition of p38 MAPK and JNK phosphorylation. CONCLUSION: Our findings suggest that the P. lobata extract has the potential to prevent AMD development by inhibiting the mechanism underlying oxidative stress-mediated ocular disorders.

Aster koraiensis extract lowers postprandial glucose in normoglycemic and high-fat-diet-induced obese mice.

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.

Improvement in Diabetic Retinopathy through Protection against Retinal Apoptosis in Spontaneously Diabetic Torii Rats Mediated by Ethanol Extract of Osteomeles schwerinae C.K. Schneid.

Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end product (AGE) accumulation, oxidative stress, and mitochondrial function via the inhibition of NF-κB activity, in turn, through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2″-O-acetylvitexin (8-C-(2″-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in the development or disease improvement in patients of DR.

Apricot Kernel Extract and Amygdalin Inhibit Urban Particulate Matter-Induced Keratoconjunctivitis Sicca.

Exposure to particulate matter is a risk factor for various ocular surface diseases, including keratoconjunctivitis sicca (KCS). In this study, we investigated the protective effects of apricot kernel extract (AKE) and its bioactive compound, amygdalin, on KCS induced by exposure to urban particulate matter (UPM). In the in vivo experiments, eye drops containing 0.5 mg/mL AKE (AKE-0.5) or 1 mg/mL AKE (AKE-1) were administered directly into the eyes of female rats after UPM exposure. Additionally, the effect of AKE and amygdalin on matrix metalloproteinases (MMPs) activity and the expressions of inflammatory factors, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, was investigated in conjunctival epithelial cells in vitro. Topical administration of AKE-1 attenuated UPM exposure-induced reduction of tear secretion. Both AKE-0.5 and AKE-1 inhibited UPM exposure-induced corneal epithelial damage and irregularity. AKE also protected against UPM exposure-induced disruption of the mucin-4 layer on the ocular surface. In addition, AKE and amygdalin prevented UPM-induced activation of MMPs and upregulation of TNF-α and IL-6 in conjunctival epithelial cells. Therefore, AKE may have protective effects against UPM exposure-induced KCS via the inhibition of MMPs and inflammation. The pharmacological activities of AKE may be in part due to its bioactive compound, amygdalin.

Stem Cell Markers Predict the Response to Sorafenib in Patients with Hepatocellular Carcinoma.

Background/Aims: Sorafenib remains the only approved molecular targeted agent for hepatocellular carcinoma (HCC); however, reliable biomarkers that predict its efficacy are still lacking. The aim of this study was to explore whether cancer stem cell (CSC) markers have a predictive role with regard to the sorafenib response in HCC patients. Methods: We enrolled 47 patients with HCC for whom tumor samples obtained before starting sorafenib treatment were available. RNA was extracted from formalin-fixed, paraffin-embedded samples, and real-time polymerase chain reaction was used to quantify mRNA expression of the CSC genes EpCAM, CD13, CK8, CD24, CD44, CD90, CD133, SALL4, ALDH1A1, ALB, and AFP . Results: Of 47 patients, 14.9% and 74.5% had vascular invasion and extrahepatic spread, respectively. Patients with low CD133 expression tended to have longer progression-free survival (PFS) than those with high CD133 expression (5.5 months vs 4.0 months), although without statistical significance. The expression levels of other markers were not associated with PFS. When examining markers in combination, patients with high CD133 and CD90 expression had shorter PFS rates than those with low expression (2.7 months vs 5.5 months; p=0.04). Patients with low CD133 and EpCAM expression demonstrated better PFS than those with high expression (7.0 months vs 4.2 months; p=0.04). Multivariable analysis indicated that an Eastern Cooperative Oncology Group performance status score of 1 and high CD133/CD90 expression were significantly associated with shorter PFS. Conclusions: Overexpression of the CSC markers CD133 and CD90 in HCC was associated with poorer response to sorafenib. These two genes may serve as predictive biomarkers for sorafenib therapy.