• Journal of Ginseng Research
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• v.45 no.6
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• pp.706-716
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• 2021

Background: Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, is characterized by chronic abdominal pain and bowel habit changes. Although diverse complicated etiologies are involved in its pathogenesis, a dysregulated gut-brain axis may be an important factor. Red ginseng (RG), a traditional herbal medicine, is proven to have anti-inflammatory effects and improve brain function; however, these effects have not been investigated in IBS. Methods: Three-day intracolonic zymosan injections were used to induce post-infectious human IBS-like symptoms in mice. The animals were randomized to receive either phosphate-buffered saline (CG) or RG (30/100/300 mg/kg) for 10 days. Amitriptyline and sulfasalazine were used as positive controls. Macroscopic scoring was performed on day 4. Visceral pain and anxiety-like behaviors were assessed by colorectal distension and elevated plus maze and open field tests, respectively, on day 10. Next-generation sequencing of gut microbiota was performed, and biomarkers involved in gut-brain axis responses were analyzed. Results: Compared to CG, RG significantly decreased the macroscopic score, frequency of visceral pain, and anxiety-like behavior in the IBS mice. These effects were comparable to those after sulfasalazine and amitriptyline treatments. Moreover, RG significantly increased the proliferation of beneficial microbes, including Lactobacillus johnsonii, Lactobacillus reuteri, and Parabacteroides goldsteinii. RG significantly suppressed expression of IL-1β and c-fos in the gut and prefrontal cortex, respectively. Further, it restored the plasma levels of corticosterone to within the normal range, accompanied by an increase in adrenocorticotropic hormone. Conclusion: RG may be a potential therapeutic option for the management of human IBS.

• Journal of Korean Neurosurgical Society
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• v.62 no.2
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• pp.153-165
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• 2019

Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• Journal of Korean Neurosurgical Society
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• v.62 no.6
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• pp.626-634
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• 2019

Objective : Nerve growth factor (NGF) is a member of the neurotrophic factor family and plays a vital role in the physiological processes of organisms, especially in the nervous system. Many recent studies have reported that NGF is also involved in the regulation of tumourigenesis by either promoting or suppressing tumor growth, which depends on the location and type of tumor. However, little is known regarding the effect of NGF on interspinal schwannoma (IS). In the present study, we aimed to explored whether mouse nerve growth factor (mNGF), which is widely used in the clinic, can influence the growth of interspinal schwannoma cells (ISCs) isolated from IS in vitro. Methods : ISCs were isolated, cultured and identified by S-100 with immunofluorescence analysis. S-100-positive cells were divided into five groups, and separately cultured with various concentrations of mNGF (0 [phosphate buffered saline, PBS], 40, 80, 160, and 320 ng/mL) for 24 hours. Western blot and quantantive real time polymerase chain reaction (PCR) were applied to detect tyrosine kinase A (TrkA) receptor and p75 neurotrophin receptor ($p75^{NTR}$) in each group. Crystal violet staining was selected to assess the effect of mNGF (160 ng/mL) on ISCs growth. Results : ISCs growth was enhanced by mNGF in a dose-dependent manner. The result of crystal violet staining revealed that it was significantly strengthened the cells growth kinetics when cultured with 160 ng/mL mNGF compared to PBS group. Western blot and quantantive real time PCR discovered that TrkA receptor and mRNA expression were both up-regualated under the condition of mNGF, expecially in 160 ng/mL, while the exoression of $p75^{NTR}$ demonstrated no difference among groups. Conclusion : From these data, we conclude that exogenous mNGF can facilitate ISC growth by activating both TrkA receptor and $p75^{NTR}$. In addition, patients who are suffering from IS should not be administered mNGF in the clinic.

• Journal of Korean Biological Nursing Science
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• v.21 no.3
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• pp.217-223
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• 2019

Purpose: Caffeine is the most widely consumed psychostimulant of the methylxanthine class. Among adolescents, high-dose of caffeine consumption has increased rapidly over the last few decades due to the introduction of energy drinks. However, little is known about the time-dependent effect of high doses of caffeine consumption in adolescents. The present study aims to examine the short- and long-term influence of high-dose caffeine on behavior of adolescence. Methods: The animals were divided into three groups: a "vehicle" group, which was injected with 1 ml of phosphate-buffered saline for 14 days; a "Day 1" group, which was injected with caffeine (30 mg/kg), 2 h before the behavioral tests; and a "Day 14" group, which was infused with caffeine for 14 days. An open-field test, a Y-maze test, and a passive avoidance test were conducted to assess the rats'activity levels, anxiety, and cognitive function. Results: High-dose caffeine had similar effects in short-and long-term treatment groups. It increased the level of locomotor activity and anxiety-like behavior, as evidenced by the increase in the number of movements and incidences of rearing and grooming in the caffeine-treated groups. No significant differences were observed between the groups in the Y-maze test. However, in the passive avoidance test, the escape latency in the caffeine-treated group was decreased significantly, indicating impaired memory acquisition. Conclusion: These results indicate that high-dose caffeine in adolescents may increase locomotor activity and anxiety-like behavior and impair learning and memory, irrespective of the duration of administration. The findings will be valuable for both evidence-based education and clinical practice.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.2
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• pp.105-110
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• 2021

Objective: Uropathogenic Escherichia coli is known to cause urinary tract infections, and the endotoxin (lipopolysaccharide [LPS]) of this bacterium may cause deficiencies of sperm quality and morphology. In the present study, the effects of LPS on mouse sperm were studied, and the levels of interleukin (IL)-17A and possible changes in testis tissue were evaluated. Methods: LPS of uropathogenic E. coli was extracted using the methanol-chloroform method, followed confirmation using sodium dodecyl sulfate-polyacrylamide electrophoresis. Purified LPS (100 ㎍/kg) or phosphate-buffered saline was injected intraperitoneally into BALB/c mice for 7 days consecutively in the test and control groups, mice were sacrificed on days 3, 7, and 42 after the first injection. Blood was tested for levels of IL-17A using the enzyme-linked immunosorbent assay method. Testis tissue and sperm were collected from each mouse and were studied according to standard protocols. Results: The mean sperm count and motility significantly decreased (p=0.03) at 3, 7, and 42 days after the injections. The level of IL-17A in the test groups increased, but not significantly (p=0.8, p=0.11, and p=0.15, respectively). Microscopic studies showed no obvious changes in the morphology of the testis tissue; however, significant changes were observed in the cellular parenchyma on day 42. Conclusion: LPS can stimulate the immune system to produce proinflammatory cytokines, resulting in an immune response in the testis and ultimately leading to deficiency in sperm parameters and testis tissue damage. In addition, the presence of LPS could significantly impair sperm parameters, as shown by the finding of decreased motility.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.68-72
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• 2020

Purpose: Trisomy 21, the cause of Down syndrome (DS) with various medical problems, is the most common aneuploidy during the fetal period. For diagnosis, a non-invasive screening test using maternal blood, which cannot be confirmed and invasive confirmation test with a risk of miscarriage, may be performed. The trophoblast retrieval and isolation of the cervix (TRIC) have been proposed by some researchers as an alternative to overcome the limitations of current tests. We experimented using TRIC to identify the possibility of trisomy 21 for the first time in Asia. Materials and Methods: Three cases of DS were analyzed confirmed by invasive tests (chorionic villus sampling, amniocentesis). All samples of trophoblasts immediately were immersed in phosphate-buffered saline and processed with formalin for fixation. The trophoblasts were isolated using an anti-human leukocyte antigen-G antibody coupled to magnetic nanoparticles. β-human chorionic gonadotropin (hCG)-expressing cells were considered as trophoblast cells, and the detection rate calculated. DS was confirmed by fluorescence in situ hybridization (FISH). Results: The mean trophoblast detection rate using β-hCG was 78.1%, and the detection rate using FISH was 22.2%. In all cases, the trisomy of chromosome 21 was identified. Conclusion: Trophoblast can be obtained from the five weeks of gestation and has a high detection rate, so it is noted that it can replace the current prenatal genetic test. To realize the clinical application as a prenatal genetic test, we will need additional efforts to identify trisomy 21 as well as other chromosomal abnormalities in future large-scale studies.

• Archives of Plastic Surgery
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• v.48 no.4
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• pp.440-447
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• 2021

Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues. Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood. Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11). Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.78.1-78.13
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• 2022

Background: Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis. Objectives: In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites. Methods: The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied. Results: The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 ㎍/mL, respectively. The time-killing curves and live-dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver. Conclusions: Florfenicol composite nanogels might improve the treatment of SCV infections.

• Food Science of Animal Resources
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• v.42 no.6
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• pp.1061-1073
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• 2022

Receptor activator of NF-kB ligand (RANKL) is known to play a major role in bone metabolism and the immune system, and its recombinant form has been expressed in bacterial systems for research since the last two decades. However, most of these recombinant forms are used after purification or directly using living cells. Here, there were cell extracts of recombinant Lactococcus lactis expressing mouse RANKL (mRANKL) used to evaluate its biological activity in mice. Mice were divided into three groups that were fed phosphate-buffered saline (PBS), wild-type L. lactis IL1403 (WT_CE), and recombinant L. lactis expressing mRANKL (mRANKL_CE). The small intestinal transcriptome and fecal microbiome were then profiled. The biological activity of mRANKL_CE was confirmed by studying RANK-RANKL signaling in vitro and in vivo. For small intestinal transcriptome, differentially expressed genes (DEGs) were identified in the mRANKL_CE group, and no DEGs were found in the WT_CE group. In the PBS vs. mRANKL_CE gene enrichment analysis, upregulated genes were enriched for heat shock protein binding, regulation of bone resorption, and calcium ion binding. In the gut microbiome analysis, there were no critical changes among the three groups. However, Lactobacillus and Sphingomonas were more abundant in the mRANKL_CE group than in the other two groups. Our results indicate that cell extracts of mRANKL_CE can play an effective role without a significant impact on the intestine. This strategy may be useful for the development of protein drugs.

• Korean Journal of Veterinary Research
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• v.63 no.1
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• pp.6.1-6.9
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• 2023

Stroke is a major cause of death and long-term disability. Chlorogenic acid is a phenolic compound with a potent neuroprotective effect. γ-enolase is a phosphopyruvate hydratase found in mature neurons and plays an important role in neuronal survival. This study investigated whether chlorogenic acid regulates the expression of γ-enolase during cerebral ischemia. Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia. Adult male rats were used and chlorogenic acid (30 mg/kg) or phosphate buffered saline (PBS) was injected intraperitoneally 2 hours after MCAO surgery. Cerebral cortical tissues were collected 24 hours after MCAO surgery. Our proteomic approach identified the reduction of γ-enolase caused by MCAO damage and the mitigation of this reduction by chlorogenic acid treatment. Results of reverse transcription-polymerase chain reaction and Western blot analyses showed a decrease in γ-enolase expression in the PBS-treated MCAO group. However, chlorogenic acid treatment attenuated this decrease. Results of immunofluorescence staining showed the change of γ-enolase by chlorogenic acid treatment. These results demonstrated that chlorogenic acid regulates the γ-enolase expression during MCAO-induced ischemia. Therefore, we suggest that chlorogenic acid mediates the neuroprotective function by regulating the γ-enolase expression in cerebral ischemia and may be used as a therapeutic agent for brain diseases including stroke.