Publications by authors named "Jin Sook Kim"

227 Publications

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.

Nutrients 2020 Nov 24;12(12). Epub 2020 Nov 24.

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

This study investigated the effects of the -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 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.
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http://dx.doi.org/10.3390/nu12123612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759958PMC
November 2020

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

J Nat Prod 2020 11 19;83(11):3354-3362. Epub 2020 Oct 19.

College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea.

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 (-) and their non-natural derivatives (-), 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 and its derivatives and 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.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00697DOI Listing
November 2020

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

Sci Rep 2020 10 8;10(1):16838. Epub 2020 Oct 8.

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Hanyang University, 222, Wangsimni-ro,Seongdong-gu, Seoul, 04763, Republic of Korea.

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.
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http://dx.doi.org/10.1038/s41598-020-73904-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545194PMC
October 2020

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

Antioxidants (Basel) 2020 Jul 16;9(7). Epub 2020 Jul 16.

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

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, IC = 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, IC = 78.28 ± 4.24 μg/mL), as well as breaking effect on AGE-bovine serum albumin crosslinking with collagen (IC = 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.
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http://dx.doi.org/10.3390/antiox9070627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402168PMC
July 2020

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

Molecules 2020 Jun 3;25(11). Epub 2020 Jun 3.

Herbal Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon 34054, Korea.

The accumulation and formation of advanced glycation end products (AGEs) are related to diabetes and age-related disease. 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.
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http://dx.doi.org/10.3390/molecules25112605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321095PMC
June 2020

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

J Korean Acad Nurs 2020 Feb;50(1):132-146

Department of Nursing, Woosong University, Daejeon, Korea.

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, <.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.
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http://dx.doi.org/10.4040/jkan.2020.50.1.132DOI Listing
February 2020

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

Pak J Pharm Sci 2020 Jan;33(1):129-134

Department of Oral Pathology, School of Dentistry, Chonbuk National University, Jeonju, South Korea/ Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.

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.
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January 2020

Polygonum cuspidatum stem extract (PSE) ameliorates dry eye disease by inhibiting inflammation and apoptosis.

J Exerc Nutrition Biochem 2019 Dec;23(4):14-22

Purpose: Here, we aimed to determine the effect of Polygonum cuspidatum stem extract (PSE) on exorbital lacrimal gland-excised rat models and hyperosmotic stress-stimulated human conjunctival cells (HCCs).

Methods: Seven week old male Wistar rats were divided into six groups. Only the rats in the control group (NOR, n=5) did not undergo surgery. Three days after the surgery, the exorbital lacrimal gland-excised rats were randomly allocated to five groups: (1) vehicle-treated dry-eyed rats (DED, n=5); (2) PSE (10 mg/kg) treated DED rats (PSE-10, n=5); (3) PSE (100 mg/kg) treated DED rats (PSE-100, n=5); and (4) PSE (250 mg/kg) treated DED rats (PSE-250, n=5). In addition, the HCC line was co-treated with hyperosmolar media (528 mOsm) and PSE (1-100 μg/ml).

Results: PSE treatment restored the tear volume and goblet cell density by inhibiting severe corneal irregularities and damage. The treatment with PSE significantly attenuated the hyperosmolar stress-induced inflammation and cell death through the suppression of mRNA expression levels of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interferon-γ (IFN-γ), and the expression of Bcl-2-associated X protein (Bax) as well as the activation of caspase-3 in vitro.

Conclusion: The inhibitory effects of PSE treatment on dry eye disease indicate the potential of nutritional intervention by PES against inflammatory diseases without adverse effects.
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http://dx.doi.org/10.20463/jenb.2019.0026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004570PMC
December 2019

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

Nutrients 2019 Nov 15;11(11). Epub 2019 Nov 15.

Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

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 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-1β, 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.
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http://dx.doi.org/10.3390/nu11112792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893769PMC
November 2019

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

Evid Based Complement Alternat Med 2019 27;2019:5710289. Epub 2019 Aug 27.

Herbal Medicine Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea.

Background: Pueraria 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 extract can prevent cell death and decrease membrane permeability in oxidative stress-induced human retinal pigment epithelial cells.

Methods: The effects of extract on hydrogen peroxide- (HO-) 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 extract were also studied by determining cell death, reactive oxygen species (ROS) generation, and p38 mitogen-activated protein kinase (MAPK) and c-Jun -terminal kinase (JNK) phosphorylation.

Results: Our results showed that the extract inhibited ROS generation, suppressed the disruption of zonula occludens-1 (ZO-1), and reduced membrane permeability in HO-induced human retinal pigment epithelial cells. Additionally, the extract prevented the inhibition of p38 MAPK and JNK phosphorylation.

Conclusion: Our findings suggest that the extract has the potential to prevent AMD development by inhibiting the mechanism underlying oxidative stress-mediated ocular disorders.
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http://dx.doi.org/10.1155/2019/5710289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732599PMC
August 2019

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

Food Sci Biotechnol 2019 Apr 23;28(2):563-568. Epub 2018 Oct 23.

1Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yusengdae-ro, Daejeon, 34054 Republic of Korea.

The 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.
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http://dx.doi.org/10.1007/s10068-018-0497-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431321PMC
April 2019

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

Nutrients 2019 Mar 4;11(3). Epub 2019 Mar 4.

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

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 (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.
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http://dx.doi.org/10.3390/nu11030546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470872PMC
March 2019

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

Molecules 2019 Feb 12;24(3). Epub 2019 Feb 12.

Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

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.
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http://dx.doi.org/10.3390/molecules24030650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384987PMC
February 2019

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

Gut Liver 2019 05;13(3):342-348

Center for Liver Cancer,Division of Clinical Research, Research Institute, National Cancer Center, Goyang, Korea.

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 , and .

Results: Of 47 patients, 14.9% and 74.5% had vascular invasion and extrahepatic spread, respectively. Patients with low expression tended to have longer progression-free survival (PFS) than those with high 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 and expression had shorter PFS rates than those with low expression (2.7 months vs 5.5 months; p=0.04). Patients with low and 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 expression were significantly associated with shorter PFS.

Conclusions: Overexpression of the CSC markers and in HCC was associated with poorer response to sorafenib. These two genes may serve as predictive biomarkers for sorafenib therapy.
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http://dx.doi.org/10.5009/gnl18345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529171PMC
May 2019

extract improves impaired skin wound healing during hyperglycemia.

Integr Med Res 2018 Dec 22;7(4):351-357. Epub 2018 Sep 22.

Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Korea.

Background: Diabetes mellitus (DM) is one of the most common diseases found across the world. extract (AKE) has a protective effect on diabetic complications such as diabetic retinopathy. However, the effects of AKE on hyperglycemia-linked impairment of wound healing during DM have not been elucidated. In this study, we investigated the effects of AKE on delayed wound healing induced by DM.

Methods: DM was induced by intraperitoneal administration of streptozotocin (STZ; 75 mg/kg) to Sprague Dawley (SD) rats. Next, a wound was induced on the back of rats after administration of STZ. Further, AKE was prepared using an alcoholic extraction of and orally administered daily for 18 days. Wound healing was evaluated using an i migration assay and measuring the wound area . Skin tissue thickness was evaluated using hematoxylin and eosin staining. Matrix metalloprotease (MMP) activity and expression were detected using zymography and immunohistochemistry.

Results: AKE administration improved the delayed migration of keratinocytes in hyperglycemic animals. It also attenuated an increase in keratinocyte MMP-2/9 activity induced by hyperglycemia. AKE protected against DM-induced impaired wound healing in rats and prevented the degradation of skin tissue induced by DM. In addition, AKE attenuated DM-induced increase in MMP-2/9 expression in skin tissue.

Conclusions: In conclusion, AKE may promote wound healing by re-epithelization via promotion of keratinocyte migration and by attenuating the disruption of the skin tissue layer via MMP-2/9 inhibition during hyperglycemia.
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http://dx.doi.org/10.1016/j.imr.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303526PMC
December 2018

Acupuncture on the Stress-Related Drug Relapse to Seeking.

Evid Based Complement Alternat Med 2018 17;2018:5367864. Epub 2018 Oct 17.

Addiction Research Center and Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Republic of Korea.

Drug addiction is a chronic relapsing disease, which causes serious social and economic problems. The most important trial for the successful treatment of drug addiction is to prevent the high rate of relapse to drug-seeking behaviors. Opponent process as a motivational theory with excessive drug seeking in the negative reinforcement of drug dependence reflects both loss of brain reward system and recruitment of brain stress system. The negative emotional state produced by brain stress system during drug withdrawal might contribute to the intense drug craving and drive drug-seeking behaviors via negative reinforcement mechanisms. Decrease in dopamine neurotransmission in the nucleus accumbens and recruitment of corticotropin-releasing factor in the extended amygdala are hypothesized to be implicated in mediating this motivated behavior. Also, a brain stress response system is hypothesized to increase drug craving and contribute to relapse to drug-seeking behavior during the preoccupation and anticipation stage of dependence caused by the exposure to stress characterized as the nonspecific responses to any demands on the body. Acupuncture has proven to be effective for reducing drug addiction and stress-related psychiatric disorders, such as anxiety and depression. Furthermore, acupuncture has been shown to correct reversible brain malfunctions by regulating drug addiction and stress-related neurotransmitters. Accordingly, it seems reasonable to propose that acupuncture attenuates relapse to drug-seeking behavior through inhibition of stress response. In this review, a brief description of stress in relapse to drug-seeking behavior and the effects of acupuncture were presented.
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http://dx.doi.org/10.1155/2018/5367864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207895PMC
October 2018

The Protective Effect of (PCE) Aqueous Extract in a Dry Eye Model.

Nutrients 2018 Oct 19;10(10). Epub 2018 Oct 19.

Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

Dry eyes are caused by highly increased osmolarity of tear film, inflammation, and apoptosis of the ocular surface. In this study, we investigated the effect of (PCE) aqueous extract in in vivo and in vitro dry eye models. Dry eye was induced by excision of the lacrimal gland and hyperosmotic media. In vivo, oral administration of PCE in exorbital lacrimal gland-excised rats recovered tear volume and Mucin4 (MUC4) expression by inhibiting corneal irregularity and expression of inflammatory cytokines. In vitro, hyperosmotic media induced human corneal epithelial cell (HCEC) cytotoxicity though increased inflammation, apoptosis, and oxidative stress. PCE treatment significantly inhibited expression of cyclooxygenase-2 and inflammatory cytokines (interleukin-6 and tumor necrosis factor-α), and activation of NF-κB p65 in hyperosmolar stress-induced HCECs. Hyperosmolarity-induced increase in Bcl-2-associated X protein (BAX) expression and activation of cleaved poly (ADP-ribose) polymerase and caspase 3 were attenuated in a concentration-dependent manner by PCE. PCE treatment restored anti-oxidative proteins such as heme oxygenase-1 (HO-1), superoxide dismutase-1 (SOD-1), and glutathione peroxidase (GPx) in hyperosmolar stress-induced HCECs. These data demonstrate that PCE prevents adverse changes in the ocular surface and tear fluid through inhibition of hyperosmolar stress-induced inflammation, apoptosis, and oxidation, suggesting that PCE may have the potential to preserve eye health.
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http://dx.doi.org/10.3390/nu10101550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212923PMC
October 2018

Efficient recovery of recombinant CRM197 expressed as inclusion bodies in E.coli.

PLoS One 2018 18;13(7):e0201060. Epub 2018 Jul 18.

ForBioKorea Co., Ltd., Seoul, Republic of Korea.

CRM197, which retains the same inflammatory and immune-stimulant properties as diphtheria toxin but with reduced toxicity, has been used as a safe carrier in conjugated vaccines. Expression of recombinant CRM197 in E. coli is limited due to formation of inclusion bodies. Soluble expression attempts in Bacillus subtilis, P. fluorescens, Pichia pastoris, and E. coli were partially unsuccessful or did not generate yields sufficient for industrial scale production. Multiple approaches have been attempted to produce CRM197 in E. coli, which has attractive features such as high yield, simplicity, fast growth, etc., including expression of oxidative host, concurrent expression of chaperones, or periplasmic export. Recently, alternative methods for recovery of insoluble proteins expressed in E. coli were reported. Compared to traditional denaturation/refolding, these methods used the non-denaturing solubilization agent, N-lauroylsarkosine to obtain higher recovery yields of native proteins. Based on this work, here, we focused on solubilization of CRM197 from E. coli inclusion bodies. First, CRM197 was expressed as inclusion bodies by high-level expression of recombinant CRM197 in E. coli (126.8 mg/g dcw). Then bioactive CRM197 was isolated from these inclusion bodies with high yield (108.1 mg/g dcw) through solubilization with N-lauroylsarkosine including Triton X-100 and CHAPS, and purified by Ni-affinity chromatography and size-exclusion chromatography. In this study, we present a cost-effective alternative for the production of bioactive CRM197 and compare our recovery yield with yields in other production processes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201060PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051658PMC
January 2019

Prevalence of severe-profound hearing loss in South Korea: a nationwide population-based study to analyse a 10-year trend (2006-2015).

Sci Rep 2018 07 2;8(1):9940. Epub 2018 Jul 2.

Department of Otolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

To estimate prevalence of severe-profound hearing loss (HL) in South Korea, and analyse a 10-year trend of HL according to age, sex, and region by using a nationwide population-based database. Retrospective review from Korean National Health Insurance Service from 2006 to 2015. The degree of severe-profound HL was classified into six grades, based mostly on HL worse than 60 dB HL for both ears. Absolute number of HL was the highest in 2011 (0.25 million; males, 0.14 million; females, 0.11 million); it decreased gradually until 2015. Total HL prevalence was the highest in 2010 (0.5%; 251,954), and decreased annually to 2015 (0.46%; 237,272). The trend of HL prevalence showed a gradual decrease from 2010 to 2015. Prevalence of severe-profound HL was always higher in the male population (1.19 times higher than female in 2015). Prevalence of HL was higher in rural areas than in urban areas (1.4 times higher in 2015). Number of severe-profound HL in South Korea decreased gradually in all age groups annually, even though some older age groups had the highest peak in 2010-2011. Prevalence of severe-profound HL decreases gradually in all age groups annually in South Korea, although the absolute number of HL cases increases rapidly among those aged over 80 years.
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http://dx.doi.org/10.1038/s41598-018-28279-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028585PMC
July 2018

Extract Prevents Diabetes-Induced Renal Injury in Spontaneously Diabetic Torii Rats.

Evid Based Complement Alternat Med 2018 24;2018:6824215. Epub 2018 Apr 24.

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.

Mesangial cell proliferation contributes to the development of glomerulosclerosis in diabetic nephropathy. This study was aimed at determining whether (OSSC) extract can ameliorate renal damage in Spontaneously Diabetic Torii (SDT) rats. OSSC extract (100 and 250 mg/kg/day) was administered to the SDT rats through oral gavage for 17 weeks. At the end of the experiment, glucose, HbA1c, and albuminuria were measured. In addition, the levels of mesangial proliferation-related proteins were determined by western blotting and immunohistochemistry. Our results show that albuminuria, accumulation of the extracellular matrix (ECM), and renal expansion were markedly restored by OSSC extract administration. The OSSC treatment also inhibited -smooth muscle actin and transforming growth factor-1 protein expression. In addition, OSSC and its bioactive compounds hyperoside and quercitrin inhibited the platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor-B receptor (PDGFR-) ligand binding in an assay. Taken together, these results indicate that OSSC inhibits ECM accumulation and mesangial proliferation of the glomeruli in SDT rats through inhibition of the interaction between PDGF-BB and PDGFR-. OSSC has ameliorating effects on the initiation and progression of diabetes complications and can be used for the treatment of early diabetic renal dysfunction.
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http://dx.doi.org/10.1155/2018/6824215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941800PMC
April 2018

Extract and Chlorogenic Acid Inhibit Retinal Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy.

Evid Based Complement Alternat Med 2018 22;2018:6402650. Epub 2018 Apr 22.

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.

extract (AKE) is a standard dietary herbal supplement. Chlorogenic acid (CA) is the major compound present in AKE. Retinal neovascularization is a common pathophysiology of retinopathy of prematurity, diabetic retinopathy, and wet form age-related macular degeneration. In this study, we aimed to evaluate the effects of AKE and CA on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Vascular endothelial growth factor- (VEGF-) induced tube formation was assayed in human vascular endothelial cells. Experimental retinal neovascularization was induced by exposing C57BL/6 mice to 75% oxygen on postnatal day 7 (P7) and then returning them to normal oxygen pressure on P12. AKE (25 and 50 mg/kg/day) and CA (25 and 50 mg/kg/day) were administered intraperitoneally for 5 days (P12-P16). Retinal flat mounts were prepared to measure the extent of retinal neovascularization at P17. The incubation of human vascular endothelial cells with AKE and CA (1-10 g/mL) resulted in the inhibition of VEGF-mediated tube formation in a dose-dependent manner. The neovascular area was significantly smaller in AKE or CA-treated mice than in the vehicle-treated mice. These results suggest that AKE is a potent antiangiogenic agent and that its antiangiogenic activity may, in part, be attributable to the bioactive component CA.
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http://dx.doi.org/10.1155/2018/6402650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937502PMC
April 2018

Changes in microbial growth, carotenoids, and water-soluble tannin content of ripe persimmon beverage after ultra-high pressure treatment.

Food Sci Technol Int 2018 Jun 16;24(4):351-360. Epub 2018 Jan 16.

Department of Agrofood Resources, National Academy of Agricultural Science, Rural Development Administration, Iseo-myeon, Republic of Korea.

To avoid the loss of carotenoids and increasing the tannin content associated with pasteurization, we tested ultra-high pressure treatment of ripe persimmon beverage. We compared microbial counts (aerobic bacteria, coliforms, and mould), carotenoid contents, and water-soluble tannin contents between heat- and ultra-high pressure-treated beverages. No microbial contamination was detected after pasteurization or ultra-high pressure treatment at 400 MPa for more than 5 min. Ultra-high pressure treatment significantly prevented the reduction in carotenoids (lutein, zeaxanthin, β-cryptoxanthin, β-carotene, lycopene), with losses of 3.9-28.7%, as compared to the 65% loss after pasteurization. Moreover, ultra-high pressure did not induce an increase in water-soluble tannin, which causes astringent taste, whereas water-soluble tannins were increased three times by heat treatment. In conclusion, ultra-high pressure showed the same microbial control effect as pasteurization, while it did not cause carotenoid degeneration and increased tannin and thus, it better maintained the quality of ripe persimmon beverage.
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http://dx.doi.org/10.1177/1082013218754456DOI Listing
June 2018

EGHB010, a Standardized Extract of Paeoniae Radix and Glycyrrhizae Radix, Inhibits VEGF-Induced Tube Formation In Vitro and Retinal Vascular Leakage and Choroidal Neovascularization In Vivo.

Evid Based Complement Alternat Med 2017 4;2017:1568702. Epub 2017 Oct 4.

Department of Oral Pathology, School of Dentistry, Chonbuk National University, Jeonju 54896, Republic of Korea.

EGHB010 is a hot water extract of the rhizome mixture of Pallas and Fisch. Choroidal neovascularization (CNV) and vascular leakage are the common pathophysiologies of age-related macular degeneration. In this study, we aimed to evaluate the effect of EGHB010 on retinal vascular leakage and laser-induced CNV in a rat model. Vascular endothelial growth factor- (VEGF-) induced tube formation was assayed in human retinal microvascular endothelial cells. Intravitreal VEGF-induced blood-retinal barrier breakdown was assayed in Sprague-Dawley rats. Experimental CNV was induced by laser photocoagulation in Brown Norway rats. EGHB010 (50 and 100 mg/kg/day) was administered orally for 10 days after laser photocoagulation. Choroidal flat mounts were prepared to measure the lesion size of CNV. Incubation of retinal vascular endothelial cells with EGHB010 (12.5 and 25 g/mL) resulted in the inhibition of VEGF-induced tube formation in a dose-dependent manner. VEGF-mediated retinal vascular leakage was blocked by the oral administration of EGHB010. The CNV area was significantly lower in EGHB010-treated rats than in vehicle-treated rats. These results suggest that EGHB010 is a potent antiangiogenic agent. Thus, the oral administration of EGHB010 may have a beneficial effect in the treatment of vascular leakage and CNV in patients with age-related macular degeneration.
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http://dx.doi.org/10.1155/2017/1568702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646325PMC
October 2017

Rational modification of substrate binding site by structure-based engineering of a cellobiose 2-epimerase in Caldicellulosiruptor saccharolyticus.

Microb Cell Fact 2017 Dec 12;16(1):224. Epub 2017 Dec 12.

ForBioKorea Co., Ltd., Gasan digital 2-ro, Geumcheon-gu, Seoul, Republic of Korea.

Background: Lactulose, a synthetic disaccharide, has received increasing interest due to its role as a prebiotic, specifically proliferating Bifidobacilli and Lactobacilli and enhancing absorption of calcium and magnesium. The use of cellobiose 2-epimerase (CE) is considered an interesting alternative for industrial production of lactulose. CE reversibly converts D-glucose residues into D-mannose residues at the reducing end of unmodified β-1,4-linked oligosaccharides, including β-1,4-mannobiose, cellobiose, and lactose. Recently, a few CE 3D structure were reported, revealing mechanistic details. Using this information, we redesigned the substrate binding site of CE to extend its activity from epimerization to isomerization.

Results: Using superimposition with 3 known CE structure models, we identified 2 residues (Tyr114, Asn184) that appeared to play an important role in binding epilactose. We modified these residues, which interact with C2 of the mannose moiety, to prevent epimerization to epilactose. We found a Y114E mutation led to increased release of a by-product, lactulose, at 65 °C, while its activity was low at 37 °C. Notably, this phenomenon was observed only at high temperature and more reliably when the substrate was increased. Using Y114E, isomerization of lactose to lactulose was investigated under optimized conditions, resulting in 86.9 g/l of lactulose and 4.6 g/l of epilactose for 2 h when 200 g/l of lactose was used.

Conclusion: These results showed that the Y114E mutation increased isomerization of lactose, while decreasing the epimerization of lactose. Thus, a subtle modification of the active site pocket could extend its native activity from epimerization to isomerization without significantly impairing substrate binding. While additional studies are required to scale this to an industrial process, we demonstrated the potential of engineering this enzyme based on structural analysis.
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http://dx.doi.org/10.1186/s12934-017-0841-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726027PMC
December 2017

Aster koraiensis extract prevents diabetes-induced retinal vascular dysfunction in spontaneously diabetic Torii rats.

BMC Complement Altern Med 2017 Nov 23;17(1):497. Epub 2017 Nov 23.

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yusengdae-ro, Daejeon, 34054, South Korea.

Background: Aster koraiensis extract (AKE) is a standard dietary herbal supplement. The aim of this study is to investigate the inhibitory effects of AKE on diabetes-induced retinal vascular dysfunction in Spontaneously Diabetic Torii (SDT) rats.

Methods: AKE (50 and 100 mg/kg body weight/day) was administered for 16 weeks. The effects of orally administered AKE on blood glucose levels, retinal vascular leakage, apoptosis, and accumulation of advanced glycation end products (AGEs) in the retina were evaluated.

Results: SDT rats exhibited hyperglycemia and retinal vascular leakage, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was clearly detected apoptosis in the retinal microvasculature. Immunofluorescence staining revealed the accumulation of AGEs in the retinal vasculature of the SDT rats. However, oral administration of AKE for 16 weeks blocked diabetes-induced blood-retinal barrier (BRB) breakdown and the loss of occludin, which is an important tight junction protein. Apoptosis of retinal vascular cells and AGE accumulation were significantly inhibited after AKE treatment.

Conclusion: These results indicate that, as a dietary herbal supplement, AKE may have beneficial effects on patients with diabetic retinopathy.
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http://dx.doi.org/10.1186/s12906-017-1998-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701358PMC
November 2017

Polyphenols from Euphorbia pekinensis Inhibit AGEs Formation In Vitro and Vessel Dilation in Larval Zebrafish In Vivo.

Planta Med 2018 Feb 17;84(3):176-181. Epub 2017 Nov 17.

KM-Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.

To identify active compounds in the roots of for treatment of diabetic complications, an active column fraction from a 70% EtOH extract of root was purified by preparative reversed-phase high-performance liquid chromatography, leading to the isolation of a new ellagic acid derivative, 3,3'-di--methylellagic acid 4--(6"--galloyl)--D-galactopyranoside (1: ), along with three known compounds, geraniin (2: ), 3,3'-di--methylellagic acid 4---D-xylopyranoside (3: ), and ellagic acid 3,3'-dimethyl ether (4: ). The structure of the new compound was established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds 1: -4: on advanced glycation end-products (AGEs) formation were examined. All compounds exhibited considerable inhibition of AGEs formation and IC values of 0.41 - 12.33 µM, compared with those of the positive controls aminoguanidine (IC = 1122.34 µM) and quercetin (IC = 27.80 µM). In addition, the effects of 2: and 4: on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish were investigated; both compounds significantly reduced the HG-induced dilation of hyaloid-retinal vessels relative to the HG-treated control group.
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http://dx.doi.org/10.1055/s-0043-120447DOI Listing
February 2018

[Corrigendum: Evolutionary Concept Analysis of Spirituality].

J Korean Acad Nurs 2017 10;47(5):712

Department of Nursing, the Graduate School, Yonsei University, Seoul, Korea.

This corrects the article on p. 242 in vol. 47, PMID: 28470161.
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http://dx.doi.org/10.4040/jkan.2017.47.5.712DOI Listing
October 2017

and its major component, myricitrin, inhibit high glucose-induced apoptosis of human retinal pericytes.

Integr Med Res 2017 Sep 27;6(3):300-309. Epub 2017 Jul 27.

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea.

Background: The loss of retinal pericytes is one of the earliest changes associated with diabetic retinopathy (DR). Chronic hyperglycemia induces apoptosis of these cells, leading to the onset and progression of DR. In this study, we investigated the effects of () and its major component, myricitrin, on high glucose (HG)-induced apoptosis of primary human retinal pericytes (HRPs).

Methods: The effects of an ethanol extract of leaves and of myricitrin on HRP viability and apoptosis were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Reactive oxygen species (ROS) levels were measured using 2',7'-dichlorofluorescein diacetate. The activity of specificity protein 1 (Sp1), a transcription factor, was measured using a luciferase reporter assay and western blot analyses were performed to measure the expression of proteins involved in signaling and apoptosis.

Results: HG produced cytotoxic effects on HRPs, which showed increased Sp1 expression and ROS levels. extract and myricitrin significantly inhibited HG-induced apoptosis and ROS generation, and also inhibited Sp1 activity. This was evidenced by an attenuation of the HG-mediated increase in extracellular signal-regulated kinase phosphorylation.

Conclusion: These data indicate that HG-mediated induction of Sp1 is one of a number of key signaling pathways involved in HRP apoptosis, and that extracts or myricitrin may provide useful approaches to preventing and treating DR.
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http://dx.doi.org/10.1016/j.imr.2017.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605388PMC
September 2017

GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats.

BMC Complement Altern Med 2017 Aug 29;17(1):430. Epub 2017 Aug 29.

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.

Background: GS-E3D is a newly developed pectin lyase-modified red ginseng extract. The purpose of this study was to investigate the therapeutic effects of GS-E3D on diabetes-related renal dysfunction in streptozotocin-induced diabetic rats.

Method: GS-E3D (25, 50, and 100 mg/kg body weight per day) was administered for 6 weeks. The levels of blood glucose and hemoglobin A1c, and of urinary albumin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and advanced glycation end-products (AGEs) were determined. Kidney histopathology, renal accumulation of AGEs, and expression of α-smooth muscle actin (α-SMA) were also examined.

Results: Administration of GS-E3D for 6 weeks reduced urinary levels of albumin, 8-OHdG, and AGEs in diabetic rats. Mesangial expansion, renal accumulation of AGEs, and enhanced α-SMA expression were significantly inhibited by GS-E3D treatment. Oral administration of GS-E3D dose-dependently improved all symptoms of diabetic nephropathy by inhibiting renal accumulation of AGEs and oxidative stress.

Conclusion: The results of this study indicate that the use of GS-E3D as a food supplement may provide effective treatment of diabetes-induced renal dysfunction.
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http://dx.doi.org/10.1186/s12906-017-1925-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576329PMC
August 2017

Noncirrhotic hepatocellular carcinoma: etiology and occult hepatitis B virus infection in a hepatitis B virus-endemic area.

Therap Adv Gastroenterol 2017 Jul 22;10(7):529-536. Epub 2017 May 22.

Center for Liver Cancer, National Cancer Center, Korea.

Background: Although hepatocellular carcinoma (HCC) usually develops in cirrhotic livers, a minority of cases occur in noncirrhotic livers (NCLs). We investigated etiology, clinicopathological features, and occult hepatitis B virus (HBV) infection (OBI) in patients with NCL HCC in an HBV-endemic area.

Methods: A total of 710 patients who underwent resection or transplantation for HCC at the National Cancer Center (NCC), Korea, were enrolled. HCC and fibrosis stage were diagnosed pathologically.

Results: A total of 178 patients (25%) did not have cirrhosis (NCL group). The main cause of HCC was HBV infection (77.2%), followed by cryptogenic disease (11.0%). The prevalence of NCL was 19.2%, 32.5%, 50.0%, and 48.7% among patients with HBV, hepatitis C virus (HCV), alcoholic, and cryptogenic disease, respectively ( < 0.05); corresponding nonfibrosis rates were 8.1%, 0%, 19.0%, and 24.3%, respectively. The NCL group was significantly older, with a larger tumor size, smaller tumor number, lower tumor stage, and more frequent non-HBV etiology. Among non-HBV HCC cases, 130 (80.2%) had antibodies against HBV core (HBc) and 55 (38.5%) had OBI. OBI-positive rates of 0%, 31.8%, and 52.6% were detected among HCV, alcoholic, and cryptogenic HCC cases, respectively. OBI did not correlate with advanced fibrosis. The NCL and liver cirrhosis (LC) groups did not differ in median overall survival.

Conclusion: Regardless of etiology, a significant number of HCC patients, including half of nonviral cases, did not have LC. Half of cryptogenic HCC cases had OBI. This study promotes an understanding of fibrosis and OBI among patients with HCC in an HBV-endemic area.
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http://dx.doi.org/10.1177/1756283X17710247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484439PMC
July 2017