Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer / 中华肿瘤杂志

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

Echinococcus granulosus cyst fluid(EgCF) inhibits the migration and phagocytic function of mouse macrophages induced by LPS via inducing cytoskeletal rearrangement / 细胞与分子免疫学杂志

Objective To investigate the effect of Echinococcus granulosus cyst fluid(EgCF) on the cytoskeletal rearrangement and phagocytosis and the migration of macrophages induced by lipopolysaccharide(LPS). Methods Peritoneal macrophages of C57BL/6 mice were isolated and cultured in vitro, and divided into control group and LPS group and LPS combined with EgCF group. After 48 hours of treatment, filamentous actin (F-actin) changes were observed with rhodamine-labelled phalloidin staining and fluorescence microscopy; TranswellTM chamber was used to test cell migration ability and flow cytometry to test cell phagocytosis. After 1 hour of treatment, PI3K and AKT, phosphorylated AKT (p-AKT), Rac1, guanosine triphospho-Rac1 (GTP-Rac1), WASP and Arp2 protein expressions were detected with Western blot analysis. Results Compared with the control group, after LPS stimulation, macrophages were deformed significantly; pseudopodia increased; actin cytoskeleton increased and was more distributed in pseudopodia; the ability of migration and phagocytosis were significantly improved, and the expression of PI3K, p-AKT, GTP-Rac1, WASP and Arp2 proteins significantly increased. EgCF treatment caused cell shrinkage and disappearance of pseudopodia protrusions of LPS-activated cells, and led to the reduced phagocytic and migratory of cells; the protein expression of PI3K, p-AKT, GTP-Rac1, WASP and Arp2 decreased significantly compared with the LPS group. Conclusion LPS induces the migration and enhances phagocytosis of macrophages while EgCF inhibits these effects, which is related to actin cytoskeleton rearrangement.

Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL

Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.

Era-like GTP protein gene expression in rice / Expressão do gene da proteína GTP semelhante à era no arroz

The mutations are genetic changes in the genome sequences and have a significant role in biotechnology, genetics, and molecular biology even to find out the genome sequences of a cell DNA along with the viral RNA sequencing. The mutations are the alterations in DNA that may be natural or spontaneous and induced due to biochemical reactions or radiations which damage cell DNA. There is another cause of mutations which is known as transposons or jumping genes which can change their position in the genome during meiosis or DNA replication. The transposable elements can induce by self in the genome due to cellular and molecular mechanisms including hypermutation which caused the localization of transposable elements to move within the genome. The use of induced mutations for studying the mutagenesis in crop plants is very common as well as a promising method for screening crop plants with new and enhanced traits for the improvement of yield and production. The utilization of insertional mutations through transposons or jumping genes usually generates stable mutant alleles which are mostly tagged for the presence or absence of jumping genes or transposable elements. The transposable elements may be used for the identification of mutated genes in crop plants and even for the stable insertion of transposable elements in mutated crop plants. The guanine nucleotide-binding (GTP) proteins have an important role in inducing tolerance in rice plants to combat abiotic stress conditions.

Mutações são alterações genéticas nas sequências do genoma e têm papel significativo na biotecnologia, genética e biologia molecular, até mesmo para descobrir as sequências do genoma de um DNA celular junto com o sequenciamento do RNA viral. As mutações são alterações no DNA que podem ser naturais ou espontâneas e induzidas devido a reações bioquímicas ou radiações que danificam o DNA celular. Há outra causa de mutações, conhecida como transposons ou genes saltadores, que podem mudar sua posição no genoma durante a meiose ou a replicação do DNA. Os elementos transponíveis podem induzir por si próprios no genoma devido a mecanismos celulares e moleculares, incluindo hipermutação que causou a localização dos elementos transponíveis para se moverem dentro do genoma. O uso de mutações induzidas para estudar a mutagênese em plantas cultivadas é muito comum, bem como um método promissor para a triagem de plantas cultivadas com características novas e aprimoradas para a melhoria da produtividade e da produção. A utilização de mutações de inserção por meio de transposons ou genes saltadores geralmente gera alelos mutantes estáveis que são marcados quanto à presença ou ausência de genes saltadores ou elementos transponíveis. Os elementos transponíveis podem ser usados para a identificação de genes mutados em plantas de cultivo e até mesmo para a inserção estável de elementos transponíveis em plantas de cultivo mutadas. As proteínas de ligação ao nucleotídeo guanina (GTP) têm papel importante na indução de tolerância em plantas de arroz para combater as condições de estresse abiótico.

A Case of Dopa-responsive Dystonia with a Mutation in the GCH1 Gene Misdiagnosed as Cerebral Palsy for 2 Years / 대한소아신경학회지

Dopa-responsive dystonia (DRD) is characterized by lower limb-onset, diurnally fluctuating dystonia and dramatic and sustained response to levodopa treatment. Segawa disease, an autosomal dominant deficiency of guanosine triphosphate cyclohydrolase 1 (encoded by GCH1) is the most common and well-known condition manifesting as DRD. However, similar clinical manifestations can be seen in individuals with deficiencies of other enzymes that are involved in the biosynthesis of dopamine. We describe the case of an 11-year-old girl who presented with abnormal gait, which had initially begun 2 years back. The patient showed diurnally fluctuating dystonia in both legs. She was able to walk without support in the morning, but was unable to stand without support in the evening. She had been diagnosed as having spastic cerebral palsy and had been managed with physical therapy at a local rehabilitation clinic. The patient had been healthy until the development of dystonia, and did not have a history of perinatal problems or developmental delay. Routine hematologic and biochemical test results were normal. Brain magnetic resonance imaging and electroencephalography showed no abnormalities. When levodopa was administered, the patient's abnormal gait dramatically improved 1 hour after receiving the medication. Genetic testing for the GCH1 gene revealed a missense mutation (c.293C>T [p.A98V]) that has previously been reported in patients with DRD. This case demonstrated that a levodopa trial is vital for accurate and early diagnosis of DRD in patients with dystonia resulting from an unknown cause.

Guanylyl cyclase C and guanylin reduce fat droplet accumulation in cattle mesenteric adipose tissue

Guanylyl cyclase C (GC-C) is a member of a family of enzymes that metabolize GTP to cGMP and was first identified as a receptor for heat-stable enterotoxin. Guanylin (GNY) has since been identified as an endogenous ligand for GC-C in the intestine of several mammalian species. The GNY/GC-C system regulates ion transportation and pH in the mucosa. Recently, it was reported that GC-C and GNY are involved in lipid metabolism in rat mesenteric adipose tissue macrophages. To examine the role of GC-C and GNY in lipid metabolism in cattle, we used a bovine mesenteric adipocyte primary culture system and a coculture system for bovine adipocytes and GNY-/GC-C-expressing macrophages. Fat droplets were observed to accumulate in bovine mesenteric adipocytes cultured alone, whereas few fat droplets accumulated in adipocytes indirectly cocultured with macrophages. We also observed that GC-C was present in bovine mesenteric adipose tissue, and that fat droplet accumulation decreased after in vitro GNY administration. Expressions of mRNAs encoding lipogenic factors decreased significantly in adipocytes after either coculture or GNY administration. These results suggest that the GNY/GC-C system is part of the control system for lipid accumulation in bovine mesenteric adipose tissue.

Protective effects of green tea polyphenol against cisplatin-induced nephrotoxicity in rats

OBJECTIVE: This study is to compare the effects of green tea polyphenol (GTP) pre-treatment with those of GTP post-treatment on cisplatin (CP)-induced nephrotoxicity in rat. METHODS: Male Sprague-Dawley rats were randomly divided into six groups. Animals in the control group received 0.9% saline (intraperitoneal); animals in the GTP group received 0.9% saline and GTP (0.2% GTP as their sole source of drinking water); the CP group received only CP (7 mg/kg, intraperitoneal); the CP+preGTP group received GTP from two days before CP to four days after CP and the CP+postGTP group received GTP for four days after CP. CP-induced renal toxicity was evaluated by plasma creatinine and blood urea nitrogen (BUN) concentrations; kidney tissue gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (AP) activities and histopathological examinations. RESULTS: High serume creatinine and BUN concentrations were observed in CP treated rats. The GGT and AP activites were lower in kidney of CP treated rats compared to control rats. In addition, treatment with CP resulted in development of a marked tubular necrosis, and tubular dilation in kidney of rats. Pretreatment with GTP resulted in markedly reduced elevation of serum creatinine and BUN amounts and changes of GGT and AP activity in kidney induced by CP. CP-induced histopathological changes, including tubular necrosis and dilation, were ameliorated in GTP pre-treated rats, compared to CP alone or GTP post-treated rats. CONCLUSION: These results demonstrate that GTP might have some protective effect against CP-induced nephrotoxicity in rat, and GTP pre-treatment was more effective than GTP post-treatment on reduction of CP-induced renal dysfunction.

Effect of green tea intake on blood lipids, platelet aggregation, antioxidant and liver parameters in Jeju volunteer diving woman / 한국영양학회지

We investigated dietary effects of green tea powder (GTP) on plasma lipids, platelet aggregation, hemolysis, plasma TBARS, and liver enzymes. Thirty one volunteer diving women living on Jeju island consumed 4 g green tea powder daily for a period of four weeks and data for the study subjects were analyzed on the basis of diagnostic criteria for blood pressure (BP)(> or = 140/90 mmHg), plasma total cholesterol (TC)(> or = 200 mg/dL), and triglyceride (TG)(> or = 150mg/dL). Subjects with high BP had significantly higher TC and TG than those with normal BP. Subjects with higher TC had higher TG, and those with higher TG had lower HDL cholesterol. Platelet aggregation in the initial slope was significantly higher in subjects with normal BP, normal TC, or normal TG than their counterparts in high BP, TC, and TG. HDL cholesterol after GTP intake increased only in subject groups with normal BP, normal TC, or normal TG, and plasma TG after GTP intake decreased only in groups with higher BP, higher TG, or higher TC. Plasma TC and TG in subjects with normal BP increased after GTP intake. GTP intake caused a decrease in the initial slope of platelet aggregation in all subject groups with little effect on maximum aggregation. Total bilirubin showed a significant increase and GOT increased in all subject groups after GTP intake. Beneficial effects of short term intake of green tea powder might differ depending on the subject conditions in terms of blood pressure, plasma lipids, and other cardiovascular conditions. However, with the hypolipidemic, antithrombotic, and antioxidant actions of its bioactive flavonoids, long term usage of GTP or brewed green tea may provide preventive effects against cardiovascular disease.

Nucleoside Diphosphate Kinase from Microorganisms

Nucleoside diphosphate kinase (Ndk) is ubiquitous and highly conserved multifunctional key enzyme in nucleotide metabolism. It generates nucleoside triphosphates (NTPs) by transfer of gamma-phosphates from nucleoside triphosphates such as ATP or GTP to nucleoside diphosphate. The formation of an autophosphorylated enzyme intermediate is involved in that mechanism. The phosphate is usually supplied by ATP and Ndk activity in different subcellular compartments. Ndk may regulate the crucial balance between ATP and GTP or other nucleoside triphosphates. Ndk is playing an important role in bacterial pathogenesis and emerging evidences recognize multiple roles of Ndk in host-microbe interaction. Here, I review some examples of the role of Ndk in intra- and extracellular microorganism.

Study on the chaperone properties of conserved GTPases

As a large family of hydrolases, GTPases are widespread in cells and play the very important biological function of hydrolyzing GTP into GDP and inorganic phosphate through binding with it. GTPases are involved in cell cycle regulation, protein synthesis, and protein transportation. Chaperones can facilitate the folding or refolding of nascent peptides and denatured proteins to their native states. However, chaperones do not occur in the native structures in which they can perform their normal biological functions. In the current study, the chaperone activity of the conserved GTPases of Escherichia coli is tested by the chemical denaturation and chaperone-assisted renaturation of citrate synthase and α-glucosidase. The effects of ribosomes and nucleotides on the chaperone activity are also examined. Our data indicate that these conserved GTPases have chaperone properties, and may be ancestral protein folding factors that have appeared before dedicated chaperones.

Structural study of the Cdc25 domain from Ral-specific guanine-nucleotide exchange factor RalGPS1a

The guanine-nucleotide exchange factor (GEF) RalGPS1a activates small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thus regulating various downstream cellular processes. RalGPS1a is composed of an Nterminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal pleckstrin homology (PH) domain. The Cdc25 domain of RalGPS1a, which shares about 30% sequence identity with other Cdc25-domain proteins, is thought to be directly engaged in binding and activating the substrate Ral protein. Here we report the crystal structure of the Cdc25 domain of RalGPS1a. The bowl shaped structure is homologous to the Cdc25 domains of SOS and RasGRF1. The most remarkable difference between these three Cdc25 domains lies in their active sites, referred to as the helical hairpin region. Consistent with previous enzymological studies, the helical hairpin of RalGPS1a adopts a conformation favorable for substrate binding. A modeled RalGPS1a-RalA complex structure reveals an extensive binding surface similar to that of the SOS-Ras complex. However, analysis of the electrostatic surface potential suggests an interaction mode between the RalGPS1a active site helical hairpin and the switch 1 region of substrate RalA distinct from that of the SOS-Ras complex.

Clinical Characteristic of Respiratory Tract Infections in Children during Pandemic Influenza (H1N1 2009) in Korea / 감염과화학요법

BACKGROUND: Since initial emergence on pandemic influenza (H1N1 2009) in Mexico on March 2009, the first case of pandemic influenza (H1N1 2009) occured on 2 May 2009 in Korea. We describe the clinical characteristics of childhood patients from pandemic influenza (H1N1 2009) and other concurrent respiratory pathogens during early phase of the pandemic influenza in Korea. MATERIALS AND METHODS: We have retrospectively studied 959 patients under age of 15 years who have visited Department of Emergency Medicine for a diagnostic test of pandemic influenza (H1N1 2009) or treatment of flu-like illness between May and September of 2009. The pandemic influenza (H1N1 2009) was detected via real-time RT-PCR and other respiratory viruses were detected via multiplex RT-PCR. RESULTS: A total of 959 patients visited Department of Emergency Medicine at Severance Hospital. Of them, 562 were tested; 124 (12.7%) were positive for pandemic influenza (H1N1 2009). Confirmed patients of pandemic influenza (H1N1 2009) were relatively older than non-H1N1 patients (7.5 years of age vs 4.6 years, P<0.001). Among histories or symptoms of patients with flu-like illness, contact history (80%) with another patient with pandemic influenza (H1N1 2009) was an important clue of the infection in early phase of pandemic. Comparing with hospitalized patients with respiratory tract infections due to other causes, lower ESR (32.9+/-23.5 mm/hour vs 11.5+/-9.2 mm/hour), hyperkalemia (4.2+/-0.3 mmol/L vs 5.2+/-3 mmol/L) and hyponatremia (137.2+/-2.5 mmol/L vs 124+/-40.5 mmol/L) were significant laboratory finding and higher cholesterol and GTP were noticed in pandemic influenza (H1N1 2009). Ten confirmed patients with pandemic influenza (H1N1 2009) were hospitalized due to pneumonia and all of them were resolved without any complication. CONCLUSIONS: Respiratory tract infections were caused not only by pandemic influenza (H1N1 2009) virus but also various respiratory viruses. Hospitalized patients, confirmed as pandemic influenza (H1N1 2009), showed a good prognosis. Age and contact history were distinct features and could be an important clue to differentiate causes in patients with febrile respiratory symptoms.

Forskolin Changes the Relationship between Cytosolic Ca2+ and Contraction in Guinea Pig Ileum

This study was designed to clarify the mechanism of the inhibitory effect of forskolin on contraction, cytosolic Ca2+ level ([Ca2+]i), and Ca2+ sensitivity in guinea pig ileum. Forskolin (0.1 nM~10 micrometer) inhibited high K+ (25 mM and 40 mM)- or histamine (3 micrometer)-evoked contractions in a concentration-dependent manner. Histamine-evoked contractions were more sensitive to forskolin than high K+-evoked contractions. Spontaneous changes in [Ca2+]i and contractions were inhibited by forskolin (1 micrometer) without changing the resting [Ca2+]i. Forskoln (10 micrometer) inhibited muscle tension more strongly than [Ca2+]i stimulated by high K+, and thus shifted the [Ca2+]i-tension relationship to the lower-right. In histamine-stimulated contractions, forskolin (1 micrometer) inhibited both [Ca2+]i and muscle tension without changing the [Ca2+]i-tension relationship. In alpha-toxin-permeabilized tissues, forskolin (10 micrometer) inhibited the 0.3 micrometer Ca2+-evoked contractions in the presence of 0.1 mM GTP, but showed no effect on the Ca2+-tension relationship. We conclude that forskolin inhibits smooth muscle contractions by the following two mechanisms: a decrease in Ca2+ sensitivity of contractile elements in high K+-stimulated muscle and a decrease in [Ca2+]i in histamine-stimulated muscle.

A Study on the Nutrition Knowledge and Nutritional Status of Food and Nutrition Major and Physical Science Major Female Students / 대한지역사회영양학회지

The purpose of this study is to examine the nutrition knowledge, characteristics related to, nutrient intakes, anthropometrics, biochemical indices of university female students by major (food and nutrition versus physical science). Data were taken from 120 university female students (60 from each major) and the results follows. The mean age of the subjects was 19.6 years old. Most of subjects responded that they were healthy; subjects majoring in physical science scored higher in regular exercise (p < 0.01) and were more satisfied with their own body figures (p < 0.01), compared with the counterparts. The total nutrition knowledge score was 81.01 +/- 12.3 for food and nutrition majors and 72.5 +/- 15.2 points for physical science majors. (p < 0.01) The percentages of body fat were significantly higher in the food and nutrition students than the counterparts. (p < 0.001) The result of biochemical analysis showed that both groups were in normal range. But there was some statistically significant difference between groups in GTP, HDL-cholesterol and ALP levels. It suggests that regular exercise might have a positive effect on the body. This study showed that although both groups had different knowledge of nutrition, there was not much difference in the intakes of nutrients. But especially, the intakes of calcium and iron were quite low in both groups. Subjects majoring in Physical science had more lipid intake, but they had lower body fat. This suggests that regular exercise in this group might have effects on the percentages of body fat. In future study, nutrition education might be planned to increase nutrition knowledge and to connect nutrition knowledge to eating behaviors and to promote health to regular exercise. Also, the desire and the social perception for pursuing alean body figure and being underweight should be changed for optimal health

Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population

RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP- and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/ extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81~2.61, p=0.01~0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 ( A-T-C-G) or diplotype (dt) 1 ( ht1/ht1) variations had increased susceptibility to HCC (OR=1.79 ~2.78, p=0.01~0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42~0.66, p=0.006~0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

Analysis of Gene Expression Profile of AGS Cells Stimulated by Helicobacter pylori Adhesion

BACKGROUND/AIMS: Interactions between H. pylori and gastric epithelial cells contribute to gastric inflammation and epithelial damage. This study was performed to evaluate the gene expression profile of AGS cells by adhesion of H. pylori. METHODS: Changes in AGS cell gene expression induced by co-culturing with H. pylori (G69a strain) (4, 12, 24, 48 hours) were monitored using oligonucleotide microarray. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed for data validation by the Assay-on-Demand Gene Expression product method. RESULTS: A total of 270 (2.66%) and 19 genes (0.19%) were up-regulated in AGS cells by H. pylori adhesion. Gene ontology analysis showed that up-regulated genes were categorized into endolipidase activity (17 genes), receptor binding (17 genes), integrin binding (4 genes), and two down-regulated genes into GTP binding category. The expression levels of 20 up- and 5 down-regulated genes were quantified by real-time RT-PCR. Sixteen genes involving cytokine activity (IL8, IL1B, TNF), hydrolase activity (PTP4A1, ERCC1, CASP8, CASP7, ACIN1), VIP receptor activity (VIPR2), and neuropeptide Y receptor activity (GPR83) were confirmed to be up-regulated. Five genes, namely, ARF3, M17S2, DDB2, AWP1, and WTAP were confirmed to be down-regulated. CONCLUSIONS: Host genes are significantly changed by H. pylori adhesion, which might explain the gastroduodenal pathogenesis induced by H. pylori infection.

Optimal resting heart rate in adult population: factors related to the heart rate / 대한내과학회지

BACKGROUND: The resting heart rate (HR) or HR recovery after exercise is one of the important predictors of cardiovascular disease mortality. However, few studies have addressed the ideal range of the HR. We sought to define the normal HR of healthy adults who have no evidence of cardiovascular or systemic illness, and none of the component of metabolic syndrome (MS). METHODS: We analyzed a total of 20,162 asymptomatic adults, who were referred for a general health evaluation. All participants underwent careful clinical evaluation, including a detailed history, physical examination and laboratory workup. The mean HR for 30 seconds in the morning after an overnight fast was obtained. There were 7,823 subjects who were free of any component of MS. There were 935 MS patients, and 10,492 patients had > or =1 component of MS. RESULTS: The HR was faster in women. The resting HR of healthy men was 59.9+/-8.2 bpm, and that of healthy women was 63.7+/-8.5 bpm. There was significant correlation between the HR and the age of healthy adults (r=-0.008, p<0.001). The mean resting HR was higher in the MS patients than that of their healthy counterparts (67.4+/-10.6 bpm vs 62.0+/-8.6 bpm, respectively, p=0.000). A significant gradual increase of HR was observed as the numbers of MS component increased (r=0.127, p<0.001). The systolic blood pressure, fasting blood sugar, HbA1c, triglyceride, gamma GTP, uric acid and CRP were significantly correlated with HR. CONCLUSIONS: We herein newly define the optimal HR in a healthy adult population. Follow-up study is needed to clarify the role of HR as a risk stratifier.

A Case of progressive elevation of serum gamma-GTP level in ataxia-telangiectasia / 대한소아신경학회지

Ataxia-telangiectasia is an autosomal recessive disorders characterized by cerebellar ataxis, oculocutaneous telangiectasia and frequent respiratory infections due to immunoincompetence. Ataxia usually appear by age of 2 years with most patients need wheelchairs for morbility by early teenage. Speech and eye movements are also affected. Other important features are immunodeficiency, a high level of serum alpha-fetoprotein concentration, growth retardation, telangiectasia and a very high risk of a lymphoid tumor. Patients also show an increased sensitivity to ionizing radiation. We report a case of a 7-year-old girl who had ataxic gate, conjunctival telangiectasia, and frequent upper respiratory infection. Her alpha-fetoprotein was elevated and the serum IgA was decreased. The brain MRI showed prominent cerebellar atrophy. From the 1 st year of life to death, the level of serum gamma- GTP became steadily elevated up to 10 times of a normal level.

The Effect of Green Tea Extract on Cisplatin in Cervical Cancer Cell Lines / 대한산부인과학회지

OBJECTIVE: Green tea polyphenol (GTP) has been shown to have anti-tumor properties in a wide variety of experimental systems. In this study, we evaluated the effects of GTP on the cytotoxic effects of cisplatin in cultured HeLa and SiHa cells. METHODS: The cell lines from Korean Cell Culture Bank were cultured in a RPMI-1640 medium supplemented with a 10% fetal bovine serum, antibiotics streptomycin and penicillin. GTP was extracted from tea leaves (Camellia scinensis) by water extraction and organic solvent fractionation. Cells were seeded at 1 x 10(4) cells/well in RPMI1640 media in triplicate wells on a Nunc Labware 96 well flat bottom microculture plate, with and without GTP (100 microgram/mL) and at different concentrations of cisplatin (0-1000 microgram/mL). After incubating the plates at 37 degrees C in 5% CO2 for 2 days, cell viability was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; thiazolyl blue] assay. RESULTS: The viability of the HeLa cells was decreased to 14% at a 600 microgram/mL concentration of cisplatin, and to 16% at 600 microgram/mL in the SiHa cells as measured by the MTT assay. However, in the HeLa cell, co-cultured with GTP (100 microgram/mL), the cell viability decreased to 68% at 200 microgram/mL of cisplatin and to 17% at 400 microgram/mL of cisplatin. And in the SiHa cell, co-cultured with GTP (100 microgram/mL), the cell viability decreased to 48% at 200 microgram/mL of cisplatin and to 17% at 400 microgram/mL of cisplatin. CONCLUSION: This study showed that cisplatin with GTP seems to have a potentiating effect on Cisplatin cytotoxicity than cisplatin alone.

The Antiproteinuric Effects of Green Tea Polyphenol on Cyclosporine A-Induced Acute Renal Injury in Mice / 대한신장학회잡지

BACKGROUND:It has been reported that there is association between cyclosporine (CsA) nephrotoxicity and proteinuria. The aim of this study was to investigate the anti-proteinuric effects of green tea polyphenol (GTP) on CsA-induced acute renal injury in mice. METHODS:The mice (n=20) were divided into 4 groups (n=5/group); group 1 (control group) mice were intraperitoneally (IP) injected 0.9% saline, group 2 (CsA group) mice were IP injected CsA 50 mg/kg, group 3 (iNOS inhibitor group) mice were given in addition N(G)-nitro-L-arginine-methyl ester (L-NAME) 12 mmol/L by subcutaneous injection. Group 4 (GTP group) mice were given CsA by IP injection and GTP 100 mg/kg by subcutaneous injection. RESULTS:Urine protein significantly increased in group 2 (28.6+/-11.1 g/kg/day) compared to group 1 (9.1+/-5.5 g/kg/day, p<0.01) and significantly decreased in group 4 (11.2+/-8.8 g/kg/day, p<0.01) compared to group 2. Renal tissue malondialdehyde level of group 2 significantly increased compared to group 1 and significantly decreased in GTP group (p<0.01). CONCLUSION:This study proves that proteinuria of the CsA induced nephrotoxicity is associated with lipid peroxidation and nitric oxide production. GTP treatment has meaningful antiproteinuric effects through antioxidative effect in the kidney from CsA-induced acute renal injury.