Allogeneic hematopoietic cell transplantation can overcome the adverse prognosis indicated by secondary-type mutations in de novo acute myeloid leukemia.

Secondary-type mutations (STMs), namely SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2, are more frequently detected in secondary acute myeloid leukemia (AML) than in de novo AML. Whether de novo AML with STMs should be differently managed is, however, unclear. In 394 patients diagnosed with de novo AML who had a normal karyotype, the genetic profiling via targeted deep sequencing of 45 genes revealed 59 patients carrying STMs (STM+). The STM+ group showed shorter overall survival (OS) than the STM- group (5-year OS, 15.3 vs. 31.0%) (hazard ratio [HR]: 1.975, 95% confidence interval [CI]: 1.446-2.699, p < 0.001). Among the 40 STM+ patients who achieved CR, those who received allogeneic HCT (n = 15) showed better OS (5-year OS, 40.0 vs. 12.0%) (HR: 0.423, 95% CI: 0.184-0.975, p = 0.043) and relapse-free survival (5-year, 40.0 vs. 8.0%) (HR: 0.438, 95% CI: 0.189-1.015, p = 0.054) than those who received consolidation chemotherapy only. The cumulative incidence of relapse was lower in the patients who received allogeneic HCT (5-year, 33.3 vs. 60.0%) (HR: 0.288, 95% CI: 0.111-0.746, p = 0.011), and non-relapse mortality was similar between the two groups (p = 0.935). In conclusion, STM is an independent prognostic factor for adverse outcomes in AML that can be overcome by allogeneic HCT.

Serum Antibody Response Comparison and Adverse Reaction Analysis in Healthcare Workers Vaccinated with the BNT162b2 or ChAdOx1 COVID-19 Vaccine.

The COVID-19 pandemic is changing rapidly and requires different strategies to maintain immunization. In Korea, different COVID-19 vaccines are recommended and available for various populations, including healthcare workers (HCWs) at high risk of SARS-CoV-2 infection. We plan to evaluate the adverse events (AEs) and immunogenicity of the BNT162b2 and ChAdOx1 vaccines in HCWs at a single center. This cohort study included HCWs fully vaccinated with either BNT162b2 or ChAdOx1. Blood samples were taken eight weeks after the second vaccination with both COVID-19 vaccines and six months after the second vaccination from participants with the BNT162b2 vaccine. The primary endpoint for immunogenicity was the serum neutralizing antibody responses eight weeks after vaccination. The secondary endpoint was the incidence of various AEs within 28 days of each vaccination. Between 16 March and 23 June 2021, 115 participants were enrolled (65 in the ChAdOx1 group and 50 in the BNT162b2 group). Significantly higher surrogate virus neutralization test (sVNT) inhibition was observed in participants vaccinated with two doses of BNT162b2 (mean (SD) 91.4 (9.68)%) than in those vaccinated with ChAdOx1 (mean (SD) 73.3 (22.57)%). The effectiveness of the BNT162b2 vaccine was maintained across all age and gender categories. At six months after the second dose, serum antibody levels declined significantly in the BNT162b2 group. The main adverse events, including fever, myalgia, fatigue, and headache, were significantly higher in the ChAdOx1 group after the first dose, whereas, after the second dose, those AEs were significantly higher in the BNT162b2 group (p < 0.05). Two doses of either the ChAdOx1 or the BNT162b2 COVID-19 vaccine resulted in very high seropositivity among the HCWs at our center. The quality of the antibody response, measured by sVNT inhibition, was significantly better with the BNT162b2 vaccine than with the ChAdOx1 vaccine. There was no significant association between neutralizing antibody response and AE after each vaccination in our cohort.

Phytochemistry, Ethnopharmacological Uses, Biological Activities, and Therapeutic Applications of Cassia obtusifolia L.: A Comprehensive Review.

Cassia obtusifolia L., of the Leguminosae family, is used as a diuretic, laxative, tonic, purgative, and natural remedy for treating headache, dizziness, constipation, tophobia, and lacrimation and for improving eyesight. It is commonly used in tea in Korea. Various anthraquinone derivatives make up its main chemical constituents: emodin, chrysophanol, physcion, obtusifolin, obtusin, au rantio-obtusin, chryso-obtusin, alaternin, questin, aloe-emodin, gluco-aurantio-obtusin, gluco-obtusifolin, naphthopyrone glycosides, toralactone-9-ß-gentiobioside, toralactone gentiobioside, and cassiaside. C. obtusifolia L. possesses a wide range of pharmacological properties (e.g., antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and neuroprotective properties) and may be used to treat Alzheimer's disease, Parkinson's disease, and cancer. In addition, C. obtusifolia L. contributes to histamine release and antiplatelet aggregation. This review summarizes the botanical, phytochemical, and pharmacological features of C. obtusifolia and its therapeutic uses.

Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRDpos subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRDneg subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.

Next-generation sequencing-based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse.

Next-generation sequencing (NGS) has been applied to define clinically relevant somatic mutations and classify subtypes in acute myeloid leukemia (AML). Persistent allelic burden after chemotherapy is associated with higher relapse incidence, but presence of allelic burden in AML patients after receiving allogeneic hematopoietic cell transplantation (HCT) has not been examined longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring AML patients receiving HCT. Using a targeted gene panel, we performed NGS in 104 AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and post-HCT at day 21 (post-HCTD21). NGS detected 256 mutations in 90 of 104 patients at diagnosis, which showed stepwise clearances after chemotherapy and HCT. In a subset of patients, mutations were still detectable pre-HCT and post-HCT. Most post-HCT mutations originate from mutations initially detected at diagnosis. Post-HCTD21 allelic burdens in relapsed patients were higher than in nonrelapsed patients. Post-HCTD21 mutations in relapsed patients all expanded at relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF post-HCTD21 (VAF0.2%-post-HCTD21) is associated with an increased risk of relapse (56.2% vs 16.0% at 3 years; P < .001) and worse overall survival (OS; 36.5% vs 67.0% at 3 years; P = .006). Multivariate analyses confirmed that VAF0.2%-post-HCTD21 is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; P = .003) and relapse incidence (HR, 4.75; P < .001), independent of the revised European LeukemiaNet risk groups. Overall, current study demonstrates that NGS-based posttransplant monitoring in AML patients is feasible and can distinguish high-risk patients for relapse.

Kushneria konosiri sp. nov., isolated from the Korean salt-fermented seafood Daemi-jeot.

A halophilic bacterial strain, X49T, was isolated from the Korean traditional salt-fermented seafood Daemi-jeot. X49T was an obligately aerobic, Gram-stain-negative, motile, oval or rod-shaped (0.5-1.0×1.2-3.2 µm) bacterium. After 2 days of growth, colonies on Marine agar medium were orange and circular with entire margins. X49T growth was detected at 10-37 °C and pH 4.5-8.5 in the presence of 0-26 % (w/v) NaCl. The 16S rRNA gene sequence of strain X49T was most similar to that of the type strain of Kushneria marisflavi SW32T and shared a sequence similarity of 94.7-98.6 % with type strains of species of the genus Kushneria. The predominant fatty acids were C16 : 0, C18 : 1ω7c and C12 : 0 3OH. The major isoprenoid quinone was Q9 (93 %), and minor quinones were Q8 (4 %) and Q10 (3 %). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylserine, two unidentified aminolipids, two unidentified phospholipids and two unidentified lipids. The genomic DNA G+C content was 59.1 mol%. The level of the ANI value between strain X49T and K. marisflavi SW32T, the most closely related species of the genus Kushneria, was 89.32 %. Based on the low ANI value, strain X49T and its reference strains represent genotypically distinct species. Based on this polyphasic taxonomic analysis, strain X49T represents a novel species of the genus Kushneria. The name Kushneria konosiri sp. nov. is proposed and the type strain is X49T (=KACC 14623T=JCM 16805T).

Blautia faecis sp. nov., isolated from human faeces.

A strictly anoxic, Gram-stain-positive, non-motile Blautia-like bacterium, designated strain M25(T), was isolated from a human faecal sample. Strain M25(T) was negative for both catalase and oxidase activity, utilized carbohydrates as fermentable substrates, produced lactate and acetate as the major end products of glucose fermentation in PYG medium, and had a DNA G+C content of 41.6 mol%. Comparative 16S rRNA gene sequencing showed that strain M25(T) was closely related to Ruminococcus obeum ATCC 29174(T) (96.40 % 16S rRNA gene sequence similarity) and Blautia glucerasea HFTH-1(T) (96.17 %) within the family Lachnospiraceae. Straight-chain saturated and monounsaturated cellular fatty acids were also detected, the majority being C(14 : 0), C(16 : 0) and C(16 : 0) dimethyl acetal acids. Based on the phenotypic, genotypic and phylogenetic characteristics presented in this study, strain M25(T) represents a novel species within the genus Blautia for which the name Blautia faecis sp. nov. is proposed. The type strain is M25(T) ( = KCTC 5980(T) = JCM 17205(T)).

Ruegeria conchae sp. nov., isolated from the ark clam Scapharca broughtonii.

A slightly halophilic, Gram-negative, strictly aerobic, non-motile rod, designated TW15(T), was isolated from an ark clam in South Korea. Growth occurred at 10-37 °C, with 1-5% (w/v) NaCl and at pH 7.0-10.0. Optimal growth occurred at 25-30 °C, with 2% (w/v) NaCl and at pH 8.0. Strain TW15(T) exhibited both oxidase and catalase activities. The major fatty acids of strain TW15(T) were summed feature 8 (consisting of C(18:1)ω7c and/or C(18:1)ω6c) and 11-methyl C(18:1)ω7c. The predominant isoprenoid quinone was ubiquinone-10 (Q-10). The polar lipids of strain TW15(T) comprised phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified phospholipid, an unidentified aminolipid and five unidentified lipids. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain TW15(T) was most closely related to Ruegeria lacuscaerulensis DSM 11314(T) (98.0% 16S rRNA gene sequence similarity). DNA-DNA relatedness with closely related strains was <52 ± 3%. The DNA G+C content was 55.7 mol%. On the basis of phenotypic, genotypic and phylogenetic data, strain TW15(T) represents a novel species of the genus Ruegeria, for which the name Ruegeria conchae sp. nov. is proposed. The type strain is TW15(T) ( = KACC 15115(T)  = JCM 17315(T)).

Blautia stercoris sp. nov., isolated from human faeces.

Strain GAM6-1T is a novel, strictly anaerobic, non-spore-forming, Gram-stain-positive bacterium that was isolated from the faeces of a healthy individual. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain GAM6-1T was most closely related to Blautia producta ATCC 27340T (95.7 % sequence similarity), in the family Lachnospiraceae. Strain GAM6-1T did not exhibit catalase or oxidase activity. The strain's cellular fatty acids were of the straight-chain saturated and mono-unsaturated types, with C14:0 (24.10 %), C16:0 (19.09 %) and C16:0 dimethylacetal (14.35 %) predominant. Strain GAM6-1T was able to produce acid from various carbohydrates. Glucose fermentation produced acetic acid as the major short-chain fatty acid. The genomic DNA G+C content of strain GAM6-1T was 35.6 mol%. Based on phenotypic, genotypic and phylogenetic evidence, strain GAM6-1T (=KCTC 5981T=JCM 17204T) is considered to represent a novel species, for which the name Blautia stercoris sp. nov. is proposed.

Genome sequence of Brachybacterium squillarum M-6-3(T), isolated from salt-fermented seafood.

Brachybacterium squillarum M-6-3(T) was isolated from salt-fermented seafood in Korea and belongs to the Dermabacteraceae, a rather isolated family within the actinobacterial suborder Micrococcineae. Here, we present the draft genome sequence of the type strain Brachybacterium squillarum M-6-3(T) (3,191,479 bp), a Gram-positive bacterium with high (72.8%) G+C content.

Efficacy and safety of oxaliplatin, 5-Fluorouracil, and folinic Acid combination chemotherapy as first-line treatment in metastatic or recurrent gastric cancer.

PURPOSE: We retrospectively determined the efficacy and safety of the combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer. MATERIALS AND METHODS: Between January 2006 and August 2009, 39 patients with histologically-confirmed, metastatic or recurrent gastric cancer underwent chemotherapy, and the results were retrospectively investigated. The chemotherapy regimen consisted of oxaliplatin (100 mg/m(2)) and FA (200 mg/m(2); 2-hour infusion), then 5-FU (2,400 mg/m(2); 46-hour continuous infusion) every 2 weeks. RESULTS: Thirty-nine patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1 to 16). Of the 32 evaluable patients, zero patients achieved a complete response and 11 patients achieved a partial response (response rate, 28.2%). The median time-to-progression and overall survival were 4.3 months (95% confidence interval [CI], 2.0 to 6.5 months) and 9.8 months (95% CI, 3.5 to 16.0 months), respectively. The main hematologic toxicity was anemia, which was observed in 119 cycles (56.7%). Grade 3/4 neutropenia was observed in 32 cycles (15.2%). The main non-hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. No treatment-related deaths were reported. CONCLUSION: This study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.

Mesenchymal stem cell transfer suppresses airway remodeling in a toluene diisocyanate-induced murine asthma model.

PURPOSE: Severe asthma is characterized by high medication requirements to maintain good disease control or by persistent symptoms despite high medication use. The transfer of bone marrow-derived mesenchymal stem cells (BMDMSCs) to the injured lungs is a possible treatment for severe asthma. This study investigated the therapeutic effects of BMDMSCs in airway remodeling and inflammation in an experimental toluene diisocyanate (TDI)-induced asthma animal model of severe asthma. METHODS: BMDMSCs were transferred into rats after TDI inhalation. Bronchoalveolar lavage (BAL) cell profiles, histological changes including an inflammatory index and goblet cell hyperplasia, and the airway response to methacholine using plethysmography were analyzed. Smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA) protein expression were observed in lung tissue using immunohistochemical staining. The collagen content was measured in lung tissue sections and lung extracts using Masson's trichrome staining and an immunoassay kit. RESULTS: The numbers of inflammatory cells in BAL fluid, histological inflammatory index, airway response to methacholine, number of goblet cells, and amount of collagen were increased in TDI-treated rats compared with sham rats (P=0.05-0.002). BMDMSC transfer significantly reduced the TDI-induced increase in the inflammatory index and numbers of eosinophils and neutrophils in BAL fluid to levels seen in sham-treated rats (P<0.05). BMDMSC transfer significantly reduced the number of goblet cells, collagen deposition, and immune staining for SMA and PCNA with concomitant normalization of the airway response to methacholine. CONCLUSIONS: The systemic transfer of BMDMSCs effectively reduced experimental TDI-induced airway inflammation and remodeling and airway hyperreactivity.

Phase II Clinical Trial of Genexol® (Paclitaxel) and Carboplatin for Patients with Advanced Non-small Cell Lung Cancer.

PURPOSE: This phase II clinical trial was conducted to evaluate the activity and safety of a combination treatment of paclitaxel (Genexol®) plus carboplatin in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: Chemotherapy-naïve patients having histologically confirmed advanced or metastatic non-small cell lung cancer were enrolled. Genexol® was administered at 225 mg/m(2) intravenous (IV) infusion over 3 hours, followed by carboplatin (area under the concentration-time curve=6) IV on day 1 every 3 weeks. RESULTS: Twenty-eight patients were enrolled between January 2003 and January 2005. A total of 110 cycles of chemotherapy were given. The median number of chemotherapy cycles was 4. A total of 25 study patients were evaluable. On an intent-to-treat basis, there were ten partial responses (response rate 35.7%). The median time-to-progression was 3.2 months (95% confidence interval [CI], 1.5 to 4.9) and the median overall survival was 8.2 months (95% CI, 4.1 to 12.3). The main hematologic grade 3/4 toxicity was neutropenia, which was observed in 14 (50.0%) patients. The main non-hematologic toxicity was peripheral neuropathy, which was observed in 12 patients (42.9%). Grade 3/4 neuropathy occurred in 8 patients (28.6%) and three patients discontinued treatment because of neuropathy. CONCLUSION: In this trial, the combination of Genexol® and carboplatin showed significant activity as first line treatment for patients with advanced or metastatic non-small cell lung cancer. However, a modest dose reduction of Genexol® is needed due to sensory neuropathy.

Brachybacterium squillarum sp. nov., isolated from salt-fermented seafood.

A Gram-positive bacterium, strain M-6-3(T), was isolated from salt-fermented seafood in Korea. The organism grew in 0-10 % (w/v) NaCl and at 25-37 °C, with optimal growth occurring in 5 % NaCl and at 28-30 °C. The peptidoglycan type was variation A4γ with meso-diaminopimelic acid as the diagnostic cell-wall diamino acid. The polar lipid profile of strain M-6-3(T) consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unknown glycolipid. Strain M-6-3(T) contained MK-7 as the major component of the quinone system and anteiso-C(15 : 0) (62.1 %) as the predominant fatty acid. Based on 16S rRNA gene sequence similarity studies, strain M-6-3(T) was most closely related to Brachybacterium rhamnosum LMG 19848(T) (98.5 %). The G+C content of the genomic DNA was 71.5 mol% and the mean DNA-DNA hybridization value with reference strains was 14.32 ± 2.0 %. Based on phenotypic, genotypic and phylogenetic analyses, it is proposed that strain M-6-3(T) represents a novel species for which the name Brachybacterium squillarum sp. nov. is proposed; the type strain is M-6-3(T) ( = KACC 14221(T)  = JCM 16464(T)).

Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis.

BACKGROUND: No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production. METHODS: BMDMSCs were transferred 4 days after BLM inhalation. Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and deposition of collagen were analyzed. RESULTS: Nitrite, nitrate and cytokines were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic inflammation, and amount of collagen were elevated in BLM-treated rats compared to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1beta, IL-6, TNF-alpha, TGF-beta and VEGF were also higher at day 7 (p < 0.05). Degree of lymphocyte and macrophage infiltration increased steadily over time. BMDMSC transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree of neutrophilic infiltration, collagen deposition, and levels of the cytokines, nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in situ hybridization localized the engrafted cells to areas of lung injury. CONCLUSION: Systemic transfer of BMDMSCs effectively reduced the BLM-induced lung injury and fibrosis through the down-regulation of nitric oxide metabolites, and proinflammatory and angiogenic cytokines.

The role of mesenchymal stem cells in the functional improvement of chronic renal failure.

The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF). Sprague-Dawley female rats (8 weeks old, 182.2 +/- 7.2 g) underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 x 10(6) cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-h urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients. No significant differences in blood urea nitrogen and creatinine concentration were observed between the MSC group and the untreated CRF group. However, the weight gain in the MSC group was greater than those in the CRF group after 4 months. Proteinuria in the MSC group was less than that in the CRF group over time. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between these two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis. These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.

Usefulness of umbilical cord blood cells in era of hematopoiesis research.

Although worldwide experience with umbilical cord blood (UCB) transplantation is still relatively limited, clinical experience with UCB transplantation is encouraging. The use of UCB for hematopoietic stem cell transplantation (HSCT) has advantages and disadvantages. Among the advantages are rapid availability, ability to more rapidly schedule the transplant as the UCB units are stored and ready for use, the apparent reduced need for an exact human leukocyte antigen (HLA) match, and induction of a less severe graft versus host disease (GVHD) compared with bone marrow. The major limitation of reduced numbers of hematopoietic stem cells (HSC) in UCB is being addressed by basic research. It is promising that potential improvements in engraftment efficiency without increased stem cell numbers or actual increased stem cell numbers through dual UCB transplant or ex-vivo expansion might lead to improved treatment approaches. However, its therapeutic potential extends beyond the hematopoietic component suggesting regenerative potential in solid organs as well. Many different stem and progenitor cell populations have been postulated with potential ranging from embryonic like to lineage-committed progenitor cells. UCB derived MSCs have the differentiation capacity and also the therapeutic potential with regard to regenerative medicine, stromal support, immune modulation and gene therapy. Therefore, further advances are eagerly anticipated.

Cytoprotective effects of Morinda officinalis against hydrogen peroxide-induced oxidative stress in Leydig TM3 cells.

AIM: To investigate the antioxidant effects of Morinda officinalis (Morindae radix, MR) on H(2)O(2)-induced oxidative stress in cultured mouse TM3 Leydig cells. METHODS: We carried out 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lipid peroxidation, testosterone enzyme immunoassay, superoxide dismutase (SOD), and catalase (CAT) assays in Leydig TM3 cells. RESULTS: MR showed a 47.8% 2,2-diphenyl-1-picrylhydrazyl radical scavenging effect in TM3 cells with no significant cytotoxicity. Oxidative stress was induced in TM3 cells with 100 micromol H(2)O(2), and treatment of the cells with 250 microg/mL MR showed the most significant protective effect (64%, P < 0.001) in the cell viability assay with a decreased lipid peroxidation level (1.75 nmol/mg protein, P < 0.05), increased testosterone production (43.5 pg/mL), and improvements in SOD activity (7.49 units of SOD/mg protein, P < 0.001) and CAT activity (74.6 units of CAT/mg protein, P < 0.001). CONCLUSION: These findings indicate that MR, as an antioxidant, protects functions of cultured mouse TM3 Leydig cells from H(2)O(2)-induced oxidative stress.

Enhanced inhibitory effect of ultra-fine granules of red ginseng on LPS-induced cytokine expression in the monocyte-derived macrophage THP-1 cells.

Red ginseng is one of the most popular traditional medicines in Korea because its soluble hot-water extract is known to be very effective on enhancing immunity as well as inhibiting inflammation. Recently, we developed a new technique, called the HAC-gearshift system, which can pulverize red ginseng into the ultra-fine granules ranging from 0.2 to 7.0 microm in size. In this study, the soluble hot-water extract of those ultra-fine granules of red ginseng (URG) was investigated and compared to that of the normal-sized granules of red ginseng (RG). The high pressure liquid chromatographic analyses of the soluble hot-water extracts of both URG and RG revealed that URG had about 2-fold higher amounts of the ginsenosides, the biologically active components in red ginseng, than RG did. Using quantitative RT-PCR, cytokine profiling against the Escherichia coli lipopolysaccharide (LPS) in the monocyte-derived macrophage THP-1 cells demonstrated that the URG-treated cells showed a significant reduction in cytokine expression than the RG-treated ones. Transcription expression of the LPS-induced cytokines such as TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and TGF-beta was significantly inhibited by URG compared to RG. These results suggest that some biologically active and soluble components in red ginseng can be more effectively extracted from URG than RG by standard hot-water extraction.

Electroacupuncture protects against CCK-induced acute pancreatitis in rats.

OBJECTIVE: Electroacupuncture (EA) has been used to treat myalgia, adiposis and gastroenteropathy in Korea. EA as a complementary and alternative medicine has been accepted worldwide mainly for the treatment acute and chronic pain and inflammation. The aim of this study was to investigate the effects of EA on acute pancreatitis induced by cholecystokinin octapeptide (CCK) in rats. METHODS: Animals were divided into four groups: (1) a normal group; (2) a CCK-induced acute pancreatitis group; (3) a CCK-induced acute pancreatitis group treated with 100-Hz EA, and (4) a CCK-induced acute pancreatitis group treated with 2-Hz EA. High-frequency (100-Hz) and low-frequency EA (2-Hz) stimulations were applied to an acupoint equivalent to Zusanli (ST36) in rats, followed by 75 microg/kg CCK subcutaneously three times, after 1, 3 and 5 h. The entire procedure was repeated over 5 days. Repeated CCK treatment resulted in typical laboratory and morphological changes in experimentally induced pancreatitis. RESULTS: EA significantly decreased the pancreatic weight/body weight ratio in CCK-induced acute pancreatitis, increased the pancreatic levels of HSP60 and HSP72, and decreased the beta-amylase and lipase levels associated with CCK-induced acute pancreatitis. Furthermore, the release of ACTH was increased in the blood serum of the EA-treated group. CONCLUSION: EA may have protective effects against CCK-induced acute pancreatitis through the release of ACTH.