ABSTRACT
Alzheimer's disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs' expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , MicroRNAs , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Amyloid beta-Peptides/cerebrospinal fluid , Biomarkers , Brain , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/genetics , Humans , MicroRNAs/genetics , tau Proteins/cerebrospinal fluidABSTRACT
The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.
Subject(s)
COVID-19 , Asia , COVID-19/epidemiology , Europe/epidemiology , Humans , SARS-CoV-2 , Socioeconomic FactorsABSTRACT
BACKGROUND: South Korea is one of the few countries that has succeeded in flattening the curve of new COVID-19 cases and avoiding a second outbreak by implementing multiple strategies, ranging from an individual level to the population level. OBJECTIVE: We aim to discuss the unique strategies and epidemiological characteristics of COVID-19 in South Korea and present a summary of policies implemented by the Korean government during the COVID-19 pandemic. METHODS: We designed a cross-sectional study of epidemiological data published by the Korea Centers for Disease Control and Prevention on October 1, 2020. We analyzed detailed epidemiological information of COVID-19 cases, including the number of confirmed cases and resulting deaths. RESULTS: As of October 1, 2020, a total of 23,889 confirmed COVID-19 cases and 415 deaths were reported in South Korea. In this paper, we present data on the epidemiological characteristics and transmission of the disease and discuss how the South Korean government, health care providers, and society responded to the COVID-19 outbreak. CONCLUSIONS: Understanding the epidemiological characteristics of COVID-19 in South Korea and the government's successful efforts in managing the spread of the disease can provide important insights to other countries dealing with the ongoing pandemic.
Subject(s)
COVID-19/therapy , Pandemics/statistics & numerical data , SARS-CoV-2/pathogenicity , Cross-Sectional Studies , Disease Outbreaks , Epidemiologic Methods , Humans , Republic of Korea/epidemiologyABSTRACT
Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.
Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Tomography, X-Ray Computed/methods , Adolescent , COVID-19 , Child , Child, Preschool , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Female , Humans , Male , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , SARS-CoV-2ABSTRACT
Study Design: Consecutive case series. Objective: To propose a screw placement method in patients with extremely small lumbar pedicles (ESLPs) (<2 mm) to maintain screw density and correction power, without relying on the O-arm navigation system. Summary of Background Data: In scoliosis surgery, ESLPs can hinder probe passage, resulting in exclusion or substitution of the pedicle screws with a hook. Screw density affects correction power, making it necessary to maximize the number of screw placements, especially in the lumbar curve. Limited studies provide technical guidelines for screw placement in patients with ESLPs, independent of the O-arm navigation system. Methods: We enrolled 19 patients who underwent scoliosis correction surgery using our novel screw placement method for ESLPs. Clinical, radiological, and surgical parameters were assessed. After posterior exposure of the spine, the C-arm fluoroscope was rotated to obtain a true posterior-anterior view and both pedicles were symmetrically visualized. An imaginary pedicle outline was presumed based on the elliptical or linear shadow from the pedicle. The screw entry point was established at a 2 (or 10) o'clock position in the presumed pedicle outline. After adjusting the gear-shift convergence, both cortices of the transverse process were penetrated and the tip was advanced towards the lateral vertebral body wall, where an extrapedicular screw was placed with tricortical fixation. Results: Out of 90 lumbar screws in 19 patients, 33 screws were inserted using our novel method, without correction loss or complications during an average follow-up period of 28.44 months, except radiological loosening of one screw. Conclusions: Our new extrapedicular screw placement method into the vertebral body provides an easy, accurate, and safe alternative for scoliosis patients with ESLPs without relying on the O-arm navigation system. Surgeons must consider utilizing this method to enhance correction power in scoliosis surgery, regardless of the small size of the lumbar pedicle.
ABSTRACT
IMPORTANCE: Dissimilatory nitrate/nitrite reduction to ammonium (DNRA) is a microbial energy-conserving process that reduces NO3 - and/or NO2 - to NH4 +. Interestingly, DNRA-catalyzing microorganisms possessing nrfA genes are occasionally found harboring nosZ genes encoding nitrous oxide reductases, i.e., the only group of enzymes capable of removing the potent greenhouse gas N2O. Here, through a series of physiological experiments examining DNRA metabolism in one of such microorganisms, Bacillus sp. DNRA2, we have discovered that N2O may delay the transition to DNRA upon an oxic-to-anoxic transition, unless timely removed by the nitrous oxide reductases. These observations suggest a novel explanation as to why some nrfA-possessing microorganisms have retained nosZ genes: to remove N2O that may otherwise interfere with the transition from O2 respiration to DNRA.
Subject(s)
Ammonium Compounds , Nitrites , Nitrites/metabolism , Ammonium Compounds/metabolism , Nitrates/metabolism , Nitrous Oxide/metabolism , Oxidoreductases/metabolism , DenitrificationABSTRACT
In this Viewpoint we argue that primary care practitioners should receive professional education in how to directly respond to planetary health challenges. We reflect on the provision of a massive open online course (MOOC) on planetary health for primary care practitioners in the context of existing training programmes. We describe the construction, delivery, and certification of a Global South-originated MOOC and explain aspects of its rhizomatic learning theory. We share baseline information and preliminary findings collected on the initial cohort of participants, including their profiles and previous knowledge about planetary health. We suggest that this MOOC is an appropriate response to planetary health challenges, and argue that cost-free, accredited planetary health education for primary care practitioners should be provided as a public good that also fulfils individual professionals' entitlement to quality education and continuing professional development.
Subject(s)
Education, Distance , Humans , Health Education , Global Health , Primary Health CareABSTRACT
YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics.
Subject(s)
Autoimmune Diseases/metabolism , Chitinase-3-Like Protein 1/metabolism , Adipokines , Arthritis, Rheumatoid , Behcet Syndrome , Biomarkers , Chitinase-3-Like Protein 1/blood , Chitinase-3-Like Protein 1/chemistry , HumansABSTRACT
Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Coronavirus Infections/therapy , Severe Acute Respiratory Syndrome/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Animals , COVID-19/mortality , Carbamates/therapeutic use , Coronavirus Infections/mortality , Disease Models, Animal , Drug Combinations , Drug Evaluation, Preclinical , Drug Therapy, Combination/methods , Humans , Imidazoles/therapeutic use , Immunization, Passive/methods , Pyrrolidines/therapeutic use , Randomized Controlled Trials as Topic , Severe Acute Respiratory Syndrome/mortality , Sofosbuvir/therapeutic use , Treatment Outcome , Valine/analogs & derivatives , Valine/therapeutic use , COVID-19 SerotherapyABSTRACT
Human brain-like synaptic behaviors of the ferroelectric field-effect transistors (FeFETs) were emulated by introducing the metal-ferroelectric-metal-insulator-semiconductor (MFMIS) gate stacks employing Al-doped HfO2 (Al:HfO2) ferroelectric thin films even at a low operation voltage. The synaptic plasticity of the MFMIS-FETs could be gradually modulated by the partial polarization characteristics of the Al:HfO2 thin films, which were examined to be dependent on the applied pulse conditions. Based on the ferroelectric polarization switching dynamics of the Al:HfO2 thin films, the proposed devices successfully emulate biological synaptic functions, including excitatory post-synaptic current (EPSC), paired-pulse facilitation (PPF), and spike timing-dependent plasticity (STDP). The channel conductance of the FeFETs could be controlled by partially switching the ferroelectric polarization of the Al:HfO2 gate insulators by means of pulse-number and pulse-amplitude modulations. Furthermore, the 3 × 3 array integrated with the Al:HfO2 MFMIS-FETs was also fabricated, in which electrically modifiable weighted-sum operation could be well verified in the 3 × 3 synapse array configuration.
ABSTRACT
BACKGROUND: Coronavirus Disease 2019 (COVID-19) is characterized by an unpredictable disease course, ranging from asymptomatic to severe, life-threatening infections. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation forms. METHODS: We searched PubMed® and Google® (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) scans. Pooled incidence rates of clinical characteristics were analyzed using random-effect models. RESULTS: In total, 506 patients from 34 studies (68 single cases and 438 from case-series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 ± 17.17 years) than patients with abnormal radiology (39.14 ± 26.70 years) (p-value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases; ground-glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS: More than half of the patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.
Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/diagnostic imaging , Disease Progression , Humans , Pneumonia, Viral/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray ComputedABSTRACT
Metoclopramide inhibits the central and peripheral D2 receptors and is frequently prescribed in adults and children as an antiemetic or a prokinetic drug to control symptoms of upper gastrointestinal motor disorders. Metoclopramide is predominantly metabolized via N-dealkylation and it is primarily mediated by CYP2D6 which is highly polymorphic. Thus, the effects of CYP2D6 genetic polymorphism on the pharmacokinetics of metoclopramide were evaluated in this study. All volunteers were genotyped for CYP2D6 and divided into four different genotype groups (CYP2D6*wt/*wt [*wt = *1 or *2], CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10). Each subject received a single oral dose of metoclopramide 10 mg. Plasma concentrations of metoclopramide were measured by using HPLC-UV. Compared to CYP2D6*wt/*wt, AUCinf of CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 significantly increased by 1.5-, 2.3-, and 2.5-fold, respectively. Cmax also increased significantly in comparison to CYP2D6*wt/*wt across all genotype groups, with 1.5-, 1.7-, and 1.7-fold increases seen in CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 groups, respectively. The CL/F of metoclopramide decreased in CYP2D6 genotype groups with decreased function alleles, as decreases of 37%, 56% and 61% were observed in CYP2D6*wt/10, *10/10, and *5/*10 genotype groups in comparison to the CYP2D6*wt/*wt group. In conclusion, the genetic polymorphisms of CYP2D6 significantly affected metoclopramide pharmacokinetics.
Subject(s)
Cytochrome P-450 CYP2D6/genetics , Dopamine D2 Receptor Antagonists/pharmacokinetics , Metoclopramide/pharmacokinetics , Pharmacogenomic Variants , Administration, Oral , Biotransformation , Chromatography, High Pressure Liquid , Cytochrome P-450 CYP2D6/metabolism , Dopamine D2 Receptor Antagonists/administration & dosage , Genotype , Humans , Metoclopramide/administration & dosage , Models, Biological , Pharmacogenetics , Spectrophotometry, UltravioletABSTRACT
(1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631-2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221-0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670-5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.
ABSTRACT
OBJECTIVE: Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, estimating the pandemic's case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. METHODS: A proportion meta-analysis was carried out on the CFR in every country reporting COVID-19 cases. Based on these results, we performed a meta-analysis for a global COVID-19 CFR. Each analysis was performed using two different calculations of CFR: according to the calendar date and according to the days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR, concurrently based on the date of the first confirmed case as well as on a daily basis. RESULTS: For the first time, we showed that using meta-analyses according to the calendar date and days since the outbreak of the first confirmed case, were different. CONCLUSION: We propose that a CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics.
Subject(s)
COVID-19/mortality , Global Health , Humans , Pandemics , SARS-CoV-2ABSTRACT
Bias temperature stress stabilities of thin-film transistors (TFTs) using In-Ga-Zn-O (IGZO) channels prepared by the atomic layer deposition process were investigated with varying channel thicknesses (10 and 6 nm). Even when the IGZO channel thickness was reduced to 6 nm, the device exhibited good characteristics with a high saturation mobility of 15.1 cm2 V-1 s-1 and low sub-threshold swing of 0.12 V dec-1. Excellent positive and negative bias stress stabilities were also obtained. When positive bias temperature stress (PBTS) stability was tested from 40 to 80 °C for 104 s, the threshold voltages (V TH) of the device using the 6 nm-thick IGZO channel shifted negatively, and the V TH shifts increased from -0.5 to -6.9 V with the increasing temperature. Time-dependent PBTS instabilities could be explained by a stretched-exponential equation, representing a charge-trapping mechanism.
ABSTRACT
This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; it is negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down-regulation of serum glucose level in type 2 diabetes.
Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Rutin/pharmacology , 3T3-L1 Cells , Animals , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/genetics , Disease Models, Animal , Dose-Response Relationship, Drug , Down-Regulation , Fagopyrum/chemistry , Hypoglycemic Agents/isolation & purification , Mice , Mice, Inbred C57BL , Myoblasts, Skeletal/drug effects , Myoblasts, Skeletal/enzymology , Phytotherapy , Plants, Medicinal , Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Rutin/isolation & purification , Seedlings , Time FactorsABSTRACT
Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti-cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25-125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration-dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX-treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX-treated KATO3 cells than in the GBX-treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti-proliferative and pro-apoptotic effects on KATO3 cells than GBX. The anti-proliferative and/or pro-apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor-κB) and the blocking of mTOR and PKB signals.
Subject(s)
Apoptosis/drug effects , I-kappa B Proteins/metabolism , Panax/chemistry , Plant Exudates/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/metabolism , TOR Serine-Threonine Kinases/metabolism , bcl-2-Associated X Protein/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Down-Regulation , Ginsenosides/chemistry , Ginsenosides/pharmacology , Humans , NF-KappaB Inhibitor alpha , PhosphorylationABSTRACT
PEG-hemoglobin SB1 (SB1) is a polyethylene glycol (PEG)-modified hemoglobin-based oxygen carrier, intended for use as resuscitation fluid for brain stroke and as a blood substitute. An intravenous pharmacokinetics (PK) studies with SB1 was investigated in male albino Sprague-Dawley (SD) rats and male beagle dogs at doses of 5 and 12.5 ml/kg for rats and 10 ml/kg for dogs. Total hemoglobin in plasma and whole blood was determined by gamma scintillation counter-detecting 125I-radiolabelled SB1. In the 5 ml/kg rats (n = 9), the Cmax, t1/2, AUCt and Tmax were 9.055 mg equivalents/ml, 9.6 hr, 79.6 mg equivalents.hr/ml and 0.20 hr in the plasma and 4.954 mg equivalents/ml, 9.7 hr, 37.6 mg equivalents.hr/ml and 0.11 hr in the whole blood, respectively. Those parameters in the 12.5 ml/Kg of rats (n = 9) were 19.00 mg equivalents/ml, 10.6 hr, 223.5 mg equivalents.hr/ml and 0.33 hr in the plasma and 10.58 mg equivalents/ml, 16.1 hr, 99.0 mg equivalents.hr/ml and 0.33 hr in the whole blood, respectively. An increase in the dose level from 5 to 12.5 ml/kg resulted in the increase in both Cmax and AUC24, and the increases in these parameters appeared to be in proportion to the dose increment. Thus, following the 2.5-fold increase in administered dose, Cmax was increased by a factor of 2.1 in both plasma and whole blood, while AUC24 was increased by a factor of 2.8 for plasma and 2.6 for whole blood. In the dogs receiving 10 ml/kg (n = 3), the Cmax, t1/2, AUC168 and Tmax were 12.70 mg equivalents/ml, 47.2 hr, 425.7 mg equivalents.hr/ml and 0.083 hr in the plasma and 8.372 mg equivalents/ml, 50.3 hr, 241.3 mg equivalents.hr/ml and 1.003 hr in the whole blood, respectively. The present work provides an insight into the pharmacological behavior of a PEG-modified hemoglobin.