• Journal of Ginseng Research
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• v.48 no.2
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• pp.149-162
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• 2024

Ginseng, the roots of Panax species, is an important medicinal herb used as a tonic. As ginsenosides are key bioactive components of ginseng, holistic chemical profiling of them has provided many insights into understanding ginseng. Mass spectrometry has been a major methodology for profiling, which has been applied to realize numerous goals in ginseng research, such as the discrimination of different species, geographical origins, and ages, and the monitoring of processing and biotransformation. This review summarizes the various applications of ginsenoside profiling in ginseng research over the last three decades that have contributed to expanding our understanding of ginseng. However, we also note that most of the studies overlooked a crucial factor that influences the levels of ginsenosides: genetic variation. To highlight the effects of genetic variation on the chemical contents, we present our results of untargeted and targeted ginsenoside profiling of different genotypes cultivated under identical conditions, in addition to data regarding genome-level genetic diversity. Additionally, we analyze the other limitations of previous studies, such as imperfect variable control, deficient metadata, and lack of additional effort to validate causation. We conclude that the values of ginsenoside profiling studies can be enhanced by overcoming such limitations, as well as by integrating with other -omics techniques.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.202-210
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• 2024

Background: Panax ginseng Meyer polysaccharides exhibit various biological functions, like antagonizing galectin-3-mediated cell adhesion and migration. Galectin-8 (Gal-8), with its linker-joined N- and C-terminal carbohydrate recognition domains (CRDs), is also crucial to these biological processes, and thus plays a role in various pathological disorders. Yet the effect of ginseng-derived polysaccharides in modulating Gal-8 function has remained unclear. Methods: P. ginseng-derived pectin was chromatographically isolated and enzymatically digested to obtain a series of polysaccharides. Biolayer Interferometry (BLI) quantified their binding affinity to Gal-8, and their inhibitory effects on Gal-8 was assessed by hemagglutination, cell migration and T-cell apoptosis. Results: Our ginseng-derived pectin polysaccharides consist mostly of rhamnogalacturonan-I (RG-I) and homogalacturonan (HG). BLI shows that Gal-8 binding rests primarily in RG-I and its β-1,4-galactan side chains, with sub-micromolar K_D values. Both N- and C-terminal Gal-8 CRDs bind RG-I, with binding correlated with Gal-8-mediated function. Conclusion: P. ginseng RG-I pectin β-1,4-galactan side chains are crucial to binding Gal-8 and antagonizing its function. This study enhances our understanding of galectin-sugar interactions, information that may be used in the development of pharmaceutical agents targeting Gal-8.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.333-340
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• 2024

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.298-309
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• 2024

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.395-404
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• 2024

Background: Ginsenoside Rg₁ (Rg₁) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg₁ has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg₁ against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg₁ against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg₁ intervention on H9c2 cells injured by H₂O₂ showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg₁ on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg₁ was also evaluated. Conclusion: Rg₁ can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg₁, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

• Journal of Trauma and Injury
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• v.37 no.1
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• pp.48-59
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• 2024

Purpose: Research on rib fracture management has exponentially increased. Predicting fracture patterns based on the mechanism of injury (MOI) and other possible correlations may improve resource allocation and injury prevention strategies. The Chest Injury International Database (CIID) is the largest prospective repository of the operative and nonoperative management of patients with severe chest wall trauma. The purpose of this study was to determine whether the MOI is associated with the resulting rib fracture patterns. We hypothesized that specific MOIs would be associated with distinct rib fracture patterns. Methods: The CIID was queried to analyze fracture patterns based on the MOI. Patients were stratified by MOI: falls, motor vehicle collisions (MVCs), motorcycle collisions (MCCs), automobile-pedestrian collisions, and bicycle collisions. Fracture locations, associated injuries, and patient-specific variables were recorded. Heat maps were created to display the fracture incidence by rib location. Results: The study cohort consisted of 1,121 patients with a median RibScore of 2 (range, 0-3) and 9,353 fractures. The average age was 57±20 years, and 64% of patients were male. By MOI, the number of patients and fractures were as follows: falls (474 patients, 3,360 fractures), MVCs (353 patients, 3,268 fractures), MCCs (165 patients, 1,505 fractures), automobile-pedestrian collisions (70 patients, 713 fractures), and bicycle collisions (59 patients, 507 fractures). The most commonly injured rib was the sixth rib, and the most common fracture location was lateral. Statistically significant differences in the location and patterns of fractures were identified comparing each MOI, except for MCCs versus bicycle collisions. Conclusions: Different mechanisms of injury result in distinct rib fracture patterns. These different patterns should be considered in the workup and management of patients with thoracic injuries. Given these significant differences, future studies should account for both fracture location and the MOI to better define what populations benefit from surgical versus nonoperative management.

• Safety and Health at Work
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• v.14 no.4
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• pp.451-456
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• 2023

Background: We conducted a case-control study to identify high-risk occupations and exposure to occupational hazards for acute myeloid leukemia (AML). Methods: When patients with AML admitted to the Department of Hematology in the study hospital for the first time are referred to the Department of Occupational and Environmental Medicine, data on occupation are collected by investigators to evaluate work-relatedness. Community-based controls were recruited through an online survey agency, and four controls per case were matched. Occupational information was estimated using structured questionnaires covering 27 specific occupations and 32 exposure agents. Conditional logistic regression analysis was performed by pairing cases and controls. Results: In the analysis of the risk of AML according to occupational classification, a significant association was found in paint manufacturing or painting work (OR = 2.22, 95% CI: 1.03-4.81) and aircrew (OR = 6.00, 95% CI: 1.00-35.91) in males, and in pesticide industry (OR = 6.89, 95% CI: 1.69-28.07) and cokes and steel industry (OR = 2.00, 95% CI: 1.18-22.06) in ≥60 years old. Moreover, the risk of AML increased significantly as the cumulative exposure to thinners increased. In the analyses stratified by sex and age, the association between pesticide exposure and AML was significant in males (OR = 3.28, 95% CI: 1.10-9.77) and in ≥60 years old (OR = 6.22, 95% CI: 1.48-26.08). Conclusion: This case-control study identified high-risk occupational groups in the Republic of Korea including paint manufacturers and painters, aircrew, and those who are occupationally exposed to pesticides or paint thinners.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Journal of Ecology and Environment
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• v.48 no.1
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• pp.96-109
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• 2024

Background: Khyber Pakhtunkhwa government initiated the Billion Tree Tsunami Afforestation Project including regeneration and afforestation approaches. An effort was made to assess the distribution characteristics of afforested species under present and future climatic scenarios using ecological niche modelling. For sustainable forest management, landscape ecology can play a significant role. A significant change in the potential distribution of tree species is expected globally with changing climate. Ecological niche modeling provides the valuable information about the current and future distribution of species that can play crucial role in deciding the potential sites for afforestation which can be used by government institutes for afforestation programs. In this context, the potential distribution of 8 tree species, Cedrus deodara, Dalbergia sissoo, Juglans regia, Pinus wallichiana, Eucalyptus camaldulensis, Senegalia modesta, Populus ciliata, and Vachellia nilotica was modeled. Results: Maxent species distribution model was used to predict current and future distribution of tree species using bioclimatic variables along with soil type and elevation. Future climate scenarios, shared socio-economic pathways (SSP)2-4.5 and SSP5-8.5 were considered for the years 2041-2060 and 2081-2100. The model predicted high risk of decreasing potential distribution under SSP2-4.5 and SSP5-8.5 climate change scenarios for years 2041-2060 and 2081-2100, respectively. Recent afforestation conservation sites of these 8 tree species do not fall within their predicted potential habitat for SSP2-4.5 and SSP5-8.5 climate scenarios. Conclusions: Each tree species responded independently in terms of its potential habitat to future climatic conditions. Cedrus deodara and P. ciliata are predicted to migrate to higher altitude towards north in present and future climate scenarios. Habitat of D. sissoo, P. wallichiana, J. regia, and V. nilotica is practiced to be declined in future climate scenarios. Eucalyptus camaldulensis is expected to be expanded its suitability area in future with eastward shift. Senegalia modesta habitat increased in the middle of the century but decreased afterwards in later half of the century. The changing and shifting forests create challenges for sustainable landscapes. Therefore, the study is an attempt to provide management tools for monitoring the climate change-driven shifting of forest landscapes.

• Nuclear Engineering and Technology
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• v.56 no.5
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• pp.1925-1931
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• 2024

The study conducted in the northwest region of Jordan aimed to assess the levels of natural radioactivity in soil and olive mill pomace (OMP) samples. The researchers used Nal (TI) gamma-ray spectrometry to measure the activity concentrations of ²²⁶Ra, ²³²Th, ⁴⁰K, and ¹³⁷Cs in the samples. The average activity concentrations of ²²⁶Ra, ²³²Th, ⁴⁰K, and ¹³⁷Cs in the soil samples were found to be 18.624 ± 5.82, 12.276 ± 5.728, 518.33 ± 212.57, and 0.140 ± 0.09 (Bq, kg^-1), respectively. In the OMP samples, the average activity concentrations of ²²⁶Ra, ²³²Th, and ⁴⁰K were 7.272 ± 4.386, 3.454 ± 1.503, and 169.997 ± 81.873 (Bq kg^-1), respectively, and no ¹³⁷Cs was detected. The study also investigated fundamental parameters associated with radon, specifically the radon emanation coefficient (Rn_EC) and radon mass exhalation rate (E_x). The Rn_EC values ranged from 0.621 to 0.78 (Bq kg^-1), with an average value of 0.71 ± 0.06 (Bq kg^-1). The estimated E_x from the soil samples ranged from 65.83 to 124.86 (mBq kg^-1h^-1), with an average value of 99.74 ± 21.73 (mBq kg^-1h^-1). Regarding radiological hazards, the study examined various parameters, including radium equivalent activity, external and internal hazard indices, gamma and alpha indices, absorbed gamma dose rate, and excess lifetime cancer risk. All of these assessed values were found to be below the worldwide recommended limits for radiological safety. Additionally, the study analyzed the concentrations of gross alpha and gross beta radioactivities in soil and OMP samples. The soil samples had an average gross alpha activity of 4.642 ± 1.04 (Bq kg^-1) and an average gross beta activity of 48.13 ± 14.50 (Bq kg^-1). The OMP samples showed an average gross alpha activity of 0.32 ± 0.27 (Bq kg^-1) and an average gross beta activity of 59.19 ± 12.94 (Bq kg^-1). Overall, the obtained results are crucial for evaluating the radiological risks associated with natural radioactivity in the northwest region of Jordan. The findings establish baseline data for comparison and reference for radioactivity levels in the environment.