Angelica Gigas (Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with ...anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology in Angelica gigas. In the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L.sup.- 1), kinetin (KN, 0, 0.5, and 1.0 mg L.sup.- 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L.sup.- 1 2,4-D + 0.5 mg L.sup.- 1 KN + 2 nM PSK, 0.5 mg L.sup.- 1 2,4-D + 0.9 mg L.sup.- 1 KN and 90 nM PSK, and 1.5 mg L.sup.- 1 2,4-D and 1 mg L.sup.- 1 KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration. This study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration in A. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.
N‐nitrosamines, widespread contaminants, can be formed from precursors in food including nitrites and amines. The effects of six cooking methods (roasting, stir frying/griddling, frying, blanching, ...boiling, and others) were investigated in terms of the concentrations of seven N‐nitrosamines including N‐nitrosodimethylamine, N‐nitrosomethylethylamine, N‐nitrosodiethylamine, N‐nitrosodibutylamine, N‐nitrosopiperidine, N‐nitrosopyrrolidine, and N‐nitrosomorpholine in Total Diet Study samples. In conclusion, N‐nitrosodimethylamine, N‐nitrosodiethylamine, and N‐nitrosopyrrolidine increased during boiling (5.26, 1.42, and 1.31 μg/kg each, p < .05), N‐nitrosodiethylamine contents increased in blanching, roasting induced N‐nitrosodimethylamine increases, and microwave heating increased N‐nitrosodiethylamine concentration (0.25, 1.73, and 0.15 μg/kg each, p < .05). Overall, N‐nitrosodimethylamine was the most frequently detected N‐nitrosamine (51.0%), boiling produced the most N‐nitrosamine, and N‐nitrosamines were found most frequently in fish samples. Based on the results, we recommend avoiding boiling or discarding boiled water to reduce risk from the food‐borne N‐nitrosamines. This research could improve our understanding of N‐nitrosamine changes by cooking in wide ranges of food products.
Practical applications
N‐nitrosamines can increase during boiling, blanching, roasting, and microwave heating. Boiling fish and cooking with seasoning might cause significant increases in N‐nitrosamines. Because N‐nitrosamines are not good for humans, cooking methods and food ingredients should be considered carefully.
Whereas green tea has historically been consumed in high quantities in Northeast Asia, its popularity is also increasing in many Western countries. Green tea is an abundant source of plant ...polyphenols exhibiting numerous effects that are potentially beneficial for human health. Accumulating evidence suggests that green tea polyphenols confer protective effects on the skin against ultraviolet (UV) irradiation-induced acceleration of skin aging, involving antimelanogenic, antiwrinkle, antioxidant, and anti-inflammatory effects as well as prevention of immunosuppression. Melanin pigmentation in the skin is a major defense mechanism against UV irradiation, but pigmentation abnormalities such as melasma, freckles, senile lentigines, and other forms of melanin hyperpigmentation can also cause serious health and aesthetic issues. Furthermore, UV irradiation initiates the degradation of fibrillar collagen and elastic fibers, promoting the process of skin aging through deep wrinkle formation and loss of tissue elasticity. UV irradiation-induced formation of free radicals also contributes to accelerated photoaging. Additionally, immunosuppression caused by UV irradiation plays an important role in photoaging and skin carcinogenesis. In this review, we summarize the current literature regarding the antimelanogenic, antiwrinkle, antioxidant, and immunosuppression preventive mechanisms of green tea polyphenols that have been demonstrated to protect against UV irradiation-stimulated skin photoaging, and gauge the quality of evidence supporting the need for clinical studies using green tea polyphenols as anti-photoaging agents in novel cosmeceuticals.
The paradigm for the treatment of chronic hepatitis C (CHC) has been changed due to the development of direct acting antivirals (DAAs) of hepatitis C virus (HCV). The high sustained virologic ...response rate and ease of administration makes the DAAs approach ideal to contribute to the complete eradication of HCV. Currently, treatment options for individual patients vary depending on the genotype or subtype of HCV, presence or absence of liver cirrhosis, previous experience of antiviral treatment or resistance associated substitutions. Because of drug avalilability, cost-effectiveness, preference, compliance and greater possibility of desirable effects and presumed patient-important outcomes may vary between countries, treatment options for individual patients are different. The review focuses on the comparing the current treatment options for CHC in other continents with the 2017 Korea Association for the Study of the Liver guidelines.
Few studies have examined the association between disability and chronic obstructive pulmonary disease (COPD). We compared the trends in the annual COPD prevalence between people with and without ...disabilities, and examined the association between disability and COPD. We linked the National Health Information Database (2008-2017) with the National Disability Registration Database, which includes more than 2 million people with disabilities every year. In the 2017 dataset, people with disabilities had a higher prevalence of COPD than those without disabilities (30.6% vs. 12.5%, P < 0.001). The age-standardized prevalence rate of COPD among people without disabilities increased from 4.2 in 2008 to 10.9% in 2017 (change of 6.7%), whereas that among those with disabilities increased from 7.0 to 17.1% (change of 10.1%). In multivariate analysis, compared to people without disabilities, those with disabilities had a higher probability of having COPD (adjusted odds ratio, 1.42; 95% confidence interval 1.42-1.43). The results of subgroup analysis by disability characteristics suggested that disabilities due to failure of an organ, such as the kidney, lung, heart, or liver, and severe disabilities were particularly vulnerable to COPD. In conclusion, people with disabilities are more likely to have COPD compared to people without disabilities. Further longitudinal studies that examine cause-and-effect relationship between disability and COPD are needed to clarify this relationship and to further investigate any potential negative effects associated with the coexistence of these conditions.
Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested ...the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT.
Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR).
Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030).
HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.
•CE attenuated DFE-induced AD-like symptoms.•CE suppressed DFE-induced inflammation in the skin.•CE alleviated DFE-induced transepidermal water loss and increased skin hydration.•CE has potential ...therapeutic efficacy for the AD treatment.
Cacao beans from Theobroma cacao are an abundant source of polyphenols, particularly flavonoids. Previous studies demonstrated that cacao flavanols decrease pro-inflammatory cytokines resulting in the alleviation of allergic symptoms. We sought to investigate the effects of cacao extract (CE) on Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like symptoms. CE attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Histopathological analysis revealed that CE suppressed DFE-induced immune cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum immunoglobulin (Ig) E, chemokine; thymus and activation-regulated chemokine and macrophage-derived chemokine as well as the skin-derived cytokines interleukin (IL)-4, IL-5, and interferon-γ. CE also significantly alleviated transepidermal water loss and increased skin hydration. These results suggest that CE, a natural phytochemical-rich food, has potential therapeutic efficacy for the treatment of AD.
The complexity of the tumor microenvironment poses significant challenges in cancer therapy. Here, to comprehensively investigate the tumor-normal ecosystems, we perform an integrative analysis of ...4.9 million single-cell transcriptomes from 1070 tumor and 493 normal samples in combination with pan-cancer 137 spatial transcriptomics, 8887 TCGA, and 1261 checkpoint inhibitor-treated bulk tumors. We define a myriad of cell states constituting the tumor-normal ecosystems and also identify hallmark gene signatures across different cell types and organs. Our atlas characterizes distinctions between inflammatory fibroblasts marked by AKR1C1 or WNT5A in terms of cellular interactions and spatial co-localization patterns. Co-occurrence analysis reveals interferon-enriched community states including tertiary lymphoid structure (TLS) components, which exhibit differential rewiring between tumor, adjacent normal, and healthy normal tissues. The favorable response of interferon-enriched community states to immunotherapy is validated using immunotherapy-treated cancers (n = 1261) including our lung cancer cohort (n = 497). Deconvolution of spatial transcriptomes discriminates TLS-enriched from non-enriched cell types among immunotherapy-favorable components. Our systematic dissection of tumor-normal ecosystems provides a deeper understanding of inter- and intra-tumoral heterogeneity.
The serine-threonine mitogen-activated protein kinase kinase family member T-LAK cell-originated protein kinase (TOPK/PBK) is heavily involved in tumor development, cancer growth, apoptosis, and ...inflammation. Despite the identification of TOPK as a promising novel therapeutic target, no inhibitor of TOPK has yet been reported. In this study, we screened 36 drug candidates using an in vitro kinase assay and identified the novel TOPK inhibitor HI-TOPK-032. In vitro, HI-TOPK-032 strongly suppressed TOPK kinase activity but had little effect on extracellular signal-regulated kinase 1 (ERK1), c-jun-NH2-kinase 1, or p38 kinase activities. HI-TOPK-032 also inhibited anchorage-dependent and -independent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer cell apoptosis through regulation of the abundance of p53, cleaved caspase-7, and cleaved PARP. In vivo, administration of HI-TOPK-032 suppressed tumor growth in a colon cancer xenograft model. Our findings therefore show that HI-TOPK-032 is a specific inhibitor of TOPK both in vitro and in vivo that may be further developed as a potential therapeutic against colorectal cancer.
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