Protective effects of Acanthopanax divaricatus extract in mouse models of Alzheimer's disease

BACKGROUND

Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity.

MATERIALS/METHODS

We investigated the effects of ADA extract on two mouse models of Alzheimer''s disease (AD); intracerebroventricular injection of β-amyloid peptide (Aβ) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice.

RESULTS

Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Aβ1-42 until evaluation) effectively blocked Aβ1-42-induced impairment in passive avoidance performance, and Aβ1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1α in the hippocampus. In addition, it alleviated the Aβ1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1β in the brain.

CONCLUSIONS

The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.     

Environmental Exposure,Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms

Background

A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson’s disease (PD). This link may help to elucidate mechanisms of neurotoxicity.

Objective

We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson’s disease (PD), with an emphasis on the neurotransmitter, dopamine (DA).

Data sources

A PubMed literature search was performed using the terms “obesity” and any of the following: “C. elegans,” “central nervous system,” “neurodegeneration,” “heavy metals,” “dopamine” or “Parkinson’s disease.” We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases.

Data extraction and data synthesis

Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal-and chemical-induced neurodegeneration.

Conclusions

One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.     

Antihematotoxic Role of Bunium persicum Seed Differential Extracts in Animal Model: Reactive Oxygen Species Might Be a Contributor

Objectives

Humans have been using plants as natural medicines since prehistoric times. Bunium persicum is a rich source of oils with different biological activities such as antioxidative and antimicrobial activities. The aim of this study is to evaluate the antihematotoxic and antioxidative effects of the differential extracts of B. persicum against leukemic blood induced hematotoxicity in an animal model.

Methods

This study was performed on animals, which were divided into several groups: normal control, disease control, and groups that were administered with differential extracts of plants. We measured the concentration of free radical [reactive oxygen species (ROS)] and hematological parameters as blast cells from the tibia and femur in different groups.

Results

The ROS level and blast cells count were higher in disease control groups than in groups treated with varying amounts of B. persicum extract and the normal group. Moreover, there was an imbalance in hematological parameters in untreated and treated groups with a correlation between free radicals and plant extract administration.

Conclusion

These findings may indicate a possible link between free radicals and hematotoxicity and blast cells, while depicting a potential therapeutic role for B. persicum against ROS-induced hematotoxicity.     

Longitudinal and Cross-Sectional Genetic Diversity in the Korean Peninsula Based on the P vivax Merozoite Surface Protein Gene

Objectives

Vivax malaria has reemerged and become endemic in Korea. Our study aimed to analyze by both longitudinal and cross-sectional genetic diversity of this malaria based on the P vivax Merozoite Surface Protein (PvMSP) gene parasites recently found in the Korean peninsula.

Methods

PvMSP-1 gene sequence analysis from P vivax isolates (n = 835) during the 1996-2010 period were longitudinally analyzed and the isolates from the Korean peninsula through South Korea, the demilitarized zone and North Korea collected in 2008-2010 were enrolled in an overall analysis of MSP-1 gene diversity.

Results

New recombinant subtypes and severe multiple-cloneinfection rates were observed in recent vivax parasites. Regional variation was also observed in the study sites.

Conclusion

This study revealed the great complexity of genetic variation and rapid dissemination of genes in P vivax. It also showed interesting patterns of diversity depending, on the region in the Korean Peninsula. Understanding the parasiteninsula. Under genetic variation may help to analyze trends and assess the extent of endemic malaria in Korea.     

Hematopoietic effect of deer antler extract fermented by Bacillus subtilis on murine marrow cells

BACKGROUND/OBJECTIVES

We examined the chemical composition and the effect of fermented deer antler on hematopoietic factors in bone marrow cells.

MATERIALS/METHODS

For the preparation of fermented deer antler extract (FAB), fermentation was carried out using Bacillus subtilis at 30℃ for 7 days. The hematopoietic effect of FAB was investigated hematopoietic factors in marrow cells.

RESULTS

The contents of total sugar, sulfated glycosaminoglycans, and uronic acid and the dry weight gradually increased with fermentation time. The sialic acid content (from 0.14 mg/mL to 0.54 mg/mL) was the highest on the 4th day of fermentation after which it decreased. The proliferating activity of bone marrow cells increased with fermentation times. The levels of various hematopoietic growth factors were determined to verify the beneficial effect of deer antler extract fermented by B. subtilis on hematopoiesis. FAB increased the number of stem cell factors and granulocyte colony-stimulating factor in bone marrow cells. In addition, FAB augmented the burst-forming unit erythroid and total colonies in splenocyte-conditioned medium compared with non-fermented antler extract (NFA). However, FAB did not affect the mRNA levels of erythropoietin, an important factor for erythropoiesis.

CONCLUSIONS

FAB, like NFA, did not directly affect hematopoiesis, but contributed to hematopoiesis by stimulating the production of hematopoietic factors.     

Cordyceps militaris alleviates non-alcoholic fatty liver disease in ob/ob mice

BACKGROUND/OBJECTIVES

Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model.

MATERIALS/METHODS

Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined.

RESULTS

Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels.

CONCLUSIONS

These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.     

Inhibitory effects of Doenjang,Korean traditional fermented soybean paste,on oxidative stress and inflammation in adipose tissue of mice fed a high-fat diet

BACKGROUND/OBJECTIVES

Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice.

MATERIALS/METHODS

Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks.

RESULTS

Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and p40^phox), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang.

CONCLUSIONS

Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.     

Cloning and Expression of Recombinant Tick-Borne Encephalitis Virus-like Particles in Pichia pastoris

Objectives

The purpose of this study was to verify the feasibility of using the glyceraldehyde-3-phosphate dehydrogenase (GAP) promotor based Pichia pastoris expression system to produce tick-borne encephalitis virus (TBEV) virus-like particles (VLPs).

Methods

The complementary DNA encoding the TBEV prM signal peptide, prM, and E proteins of TBEV Korean strain (KrM 93) was cloned into the plasmid vector pGAPZɑA, then integrated into the genome of P. pastoris, under the control of the GAP promoter. Expression of TBEV VLPs was determined by Western blotting using monoclonal antibody against TBEV envelope (E) protein.

Results

Recombinant TBEV VLPs consisting of prM and E protein were successfully expressed using the GAP promoter-based P. pastoris expression system. The results of Western blotting showed that the recombinant proteins were secreted into the culture supernatant from the P. pastoris and glycosylated.

Conclusion

This study suggests that recombinant TBEV VLPs from P. pastoris offer a promising approach to the production of VLPs for use as vaccines and diagnostic antigens.     

Emerging Pathogens and Vehicles of Food- and Water-borne Disease Outbreaks in Korea, 2007–2012

Objectives

Food- and water-borne disease outbreaks (FBDOs) are an important public health problem worldwide. This study investigated the trends in FBDOs in Korea and established emerging causal pathogens and causal vehicles.

Methods

We analyzed FBDOs in Korea by year, location, causal pathogens, and causal vehicles from 2007 to 2012. Information was collected from the FBDOs database in the Korean Centers for Disease Control and Prevention.

Results

During 2007–2012, a total of 1794 FBDOs and 48,897 patients were reported. After 2007, FBDOs and patient numbers steadily decreased over the next 2 years and then plateaued until 2011. However, in 2012, FBDOs increased slightly accompanied by a large increase in the number of affected patients. Our results highlight the emergence of norovirus and pathogenic Escherichia coli other than enterohemorrhagic E. coli (EHEC) in schools in 2012. We found that pickled vegetables is an emerging causal vehicle responsible for this problem.

Conclusion

On the basis of this study we recommend intensified inspections of pickled vegetable manufacturers and the strengthening of laboratory surveillance of relevant pathogens.     

Detection of Acanthamoeba and Toxoplasma in River Water Samples by Molecular Methods in Iran

Background:

Free-living amoebae such as Acanthamoeba species may act as carriers of Cryptosporidium and Toxoplasma oocysts, thus, may play an important role in the water-borne transmission of these parasites. In the present study, a loop mediated isothermal amplification (LAMP) method for detection of Toxoplasma and a PCR assay were developed for investigation of Acanthamoeba in environmental water samples.

Methods:

A total of 34 samples were collected from the surface water in Guilan Province. Water samples were filtrated with membrane filters and followed by DNA extraction. PCR and LAMP methods used for detection of the protozoan parasites Acanthamoeba and Toxoplasma respectively.

Results:

Totally 30 and 2 of 34 samples were positive for Acanthamoeba and Toxoplasma oocysts respectively. Two samples were positive for both investigated parasites.

Conclusion:

The investigated water supplies, are contaminated by Toxoplasma and Acanthamoeba (oo)cystes. Acanthamoeba may play an important role in water-borne transmission of Toxoplasma in the study area. For the first time in Iran, protocol of LAMP method was used effectively for the detection of Toxoplasma in surface water samples in Iran.     

Sargassum coreanum extract alleviates hyperglycemia and improves insulin resistance in db/db diabetic mice

BACKGROUND/OBJECTIVES

The goal of this study was to examine the effect of Sargassum coreanum extract (SCE) on blood glucose concentration and insulin resistance in C57BL-KsJ-db/db mice.

MATERIALS/METHODS

For 6 weeks, male C57BL/KsJ-db/db mice were administrated SCE (0.5%, w/w), and rosiglitazone (0.005%, w/w).

RESULTS

A supplement of the SCE for 6 weeks induced a significant reduction in blood glucose and glycosylated hemoglobin concentrations, and it improved hyperinsulinemia compared to the diabetic control db/db mice. The glucokinase activity in the hepatic glucose metabolism increased in the SCE-supplemented db/db mice, while phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities in the SCE-supplemented db/db mice were significantly lower than those in the diabetic control db/db mice. The homeostatic index of insulin resistance was lower in the SCE-supplemented db/db mice than in the diabetic control db/db mice.

CONCLUSIONS

These results suggest that a supplement of the SCE lowers the blood glucose concentration by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.     

Active and Passive Surveillance and Phylogenetic Analysis of Borrelia burgdorferi Elucidate the Process of Lyme Disease Risk Emergence in Canada

Background

Northward expansion of the tick Ixodes scapularis is driving Lyme disease (LD) emergence in Canada. Information on mechanisms involved is needed to enhance surveillance and identify where LD risk is emerging.

Objectives

We used passive and active surveillance and phylogeographic analysis of Borrelia burgdorferi to investigate LD risk emergence in Quebec.

Methods

In active surveillance, we collected ticks from the environment and from captured rodents. B. burgdorferi transmission was detected by serological analysis of rodents and by polymerase chain reaction assays of ticks. Spatiotemporal trends in passive surveillance data assisted interpretation of active surveillance. Multilocus sequence typing (MLST) of B. burgdorferi in ticks identified likely source locations of B. burgdorferi.

Results

In active surveillance, we found I. scapularis at 55% of sites, and we were more likely to find them at sites with a warmer climate. B. burgdorferi was identified at 13 I. scapularis–positive sites, but infection prevalence in ticks and animal hosts was low. Low infection prevalence in ticks submitted in passive surveillance after 2004—from the tick-positive regions identified in active surveillance—coincided with an exponential increase in tick submissions during this time. MLST analysis suggested recent introduction of B. burgdorferi from the northeastern United States.

Conclusions

These data are consistent with I. scapularis ticks dispersed from the United States by migratory birds, founding populations where the climate is warmest, and then establishment of B. burgdorferi from the United States several years after I. scapularis have established. These observations provide vital information for public health to minimize the impact of LD in Canada.     

Mathematical Modeling of Vibrio vulnificus Infection in Korea and the Influence of Global Warming

Objectives

To investigate the possible link between Vibrio vulnificus population size in seawater and water temperature.

Methods

We collected incidence and water temperature data in coastal regions of Korea and constructed a mathematical model that consisted of three classes; susceptible fish, infected fish available to humans, and infected humans.

Results

We developed a mathematical model to connect V. vulnificus incidence with water temperature using estimated bacterial population sizes and actual coastal water temperatures.

Conclusion

Increased V. vulnificus population sizes in marine environments may increase the risk of infection in people who eat at coastal restaurants in Korea. Furthermore, we estimated the near-future number of infected patients using our model, which will help to establish a public-health policy to reduce the disease burden.     

Hypoglycemic and antioxidant effects of Daraesoon (Actinidia arguta shoot) in animal models of diabetes mellitus

BACKGROUND/OBJECTIVES

The primary objective of the treatment of diabetes mellitus is the attainment of glycemic control. Hyperglycemia increases oxidative stress which contributes to the progression of diabetic complications. Thus, the purpose of this study was to investigate the hypoglycemic and antioxidant effects of Daraesoon (Actinidia arguta shoot) in animal models of diabetes mellitus.

MATERIALS/METHODS

Rats with streptozotocin-induced diabetes received an oral administration of a starch solution (1 g/kg) either with or without a 70% ethanol extract of Daraesoon (400 mg/kg) or acarbose (40 mg/kg) after an overnight fast and their postprandial blood glucose levels were measured. Five-week-old C57BL/6J mice were fed either a basal or high-fat/high-sucrose (HFHS) diet with or without Daraesoon extract (0.4%) or acarbose (0.04%) for 12 weeks after 1 week of adaptation to determine the effects of the chronic consumption of Daraesoon on fasting hyperglycemia and antioxidant status.

RESULTS

Compared to the control group, rats that received Daraesoon extract (400 mg/kg) or acarbose (40 mg/kg) exhibited a significant reduction in the area under the postprandial glucose response curve after the oral ingestion of starch. Additionally, the long-term consumption of Daraesoon extract or acarbose significantly decreased serum glucose and insulin levels as well as small intestinal maltase activity in HFHS-fed mice. Furthermore, the consumption of Daraesoon extract significantly reduced thiobarbituric acid reactive substances and increased glutathione levels in the livers of HFHS-fed mice compared to HFHS-fed mice that did not ingest Daraesoon.

CONCLUSIONS

Daraesoon effectively suppressed postprandial hyperglycemia via the inhibition of α-glucosidase in STZ-induced diabetic rats. Chronic consumption of Daraesoon alleviated fasting hyperglycemia and oxidative stress in mice fed a HFHS diet.     

Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region,Sri Lanka

Objectives

The familial clustering observed in chronic kidney disease of uncertain etiology (CKDu) characterized by tubulointerstitial damages in the North Central Region of Sri Lanka strongly suggests the involvement of genetic factors in its pathogenesis. The objective of the present study is to use whole-exome sequencing to identify the genetic variants associated with CKDu.

Methods

Whole-exome sequencing of eight CKDu cases and eight controls was performed, followed by direct sequencing of candidate loci in 301 CKDu cases and 276 controls.

Results

Association study revealed rs34970857 (c.658G > A/p.V220M) located in the KCNA10 gene encoding a voltage-gated K channel as the most promising SNP with the highest odds ratio of 1.74. Four rare variants were identified in gene encoding Laminin beta2 (LAMB2) which is known to cause congenital nephrotic syndrome. Three out of four variants in LAMB2 were novel variants found exclusively in cases.

Conclusion

Genetic investigations provide strong evidence on the presence of genetic susceptibility for CKDu. Possibility of presence of several rare variants associated with CKDu in this population is also suggested.     

Marked liver tumorigenesis by Helicobacter hepaticus requires perinatal exposure

Background

Although severe hepatitis and liver tumors occur in a high percentage of A/J male mice naturally infected with Helicobacter hepaticus, these effects have not been observed after injection of adult mice with the bacteria.

Objectives

We tested the hypothesis that perinatal exposure to the bacteria is required for liver tumorigenesis.

Methods

A/J female mice were infected by intragastric (ig) or intraperitoneal (ip) treatment with 1.5 × 10⁸ H. hepaticus before pregnancy. We examined offspring at progressive time intervals, including some kept until natural death in old age. A/J, BALB/c, and C57BL/6 weanling male mice were similarly treated ig with the bacteria and observed for up to 2 years.

Results

After ip bacterial infection of A/J females, 41% of their male offspring developed hepatitis and 33% had hepatocellular tumors, including 18% with hepatocellular carcinoma. Treatment by the ig route resulted in a similar incidence of hepatitis in offspring (35%) but fewer total liver tumors (8%) and carcinomas (4%). By contrast, ig instillation of H. hepaticus in weanling A/J, C57BL/6, or BALB/c mice resulted in low incidence of hepatitis (0–20%) and few liver tumors, despite presence of bacteria confirmed in feces.

Conclusions

Results indicate that a high incidence of liver tumors in mice infected with H. hepaticus requires perinatal exposure. Contributing perinatal factors could include known high sensitivity of neonatal liver to tumor initiation, and/or modulation of immune response to the bacterium or its toxins. Mechanisms of human perinatal sensitivity to such phenomena can be studied with this model.     

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

BACKGROUND/OBJECTIVES

This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats.

MATERIALS/METHODS

Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection.

RESULTS

Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC).

CONCLUSIONS

Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.