is an important plant genus that includes well-known species such as
,
, and
. The
cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome ...annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of
cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to
, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background and Purpose
Fulminant hepatic failure (FHF) is a fatal clinical syndrome that results in excessive inflammation and hepatocyte death. Mitochondrial dysfunction is considered to be a ...possible mechanism of FHF. Afzelin, a flavonol glycoside found in Houttuynia cordata Thunberg, has anti‐inflammatory and antioxidant properties. The present study elucidated the cytoprotective mechanisms of afzelin against D‐galactosamine (GalN)/LPS induced FHF, particularly focusing on mitochondrial quality control and dynamics.
Experimental Approach
Mice were administered afzelin i.p. 1 h before receiving GalN (800 mg·kg−1)/LPS (40 μg·kg−1), and they were then killed 5 h after GalN/LPS treatment.
Key Results
Afzelin improved the survival rate and reduced the serum levels of alanine aminotransferase and pro‐inflammatory cytokines in GalN/LPS‐treated mice. Afzelin attenuated the mitochondrial damage, as indicated by diminished mitochondrial swelling and mitochondrial glutamate dehydrogenase activity in GalN/LPS‐treated mice. Afzelin enhanced mitochondrial biogenesis, as indicated by increased levels of PPAR‐γ coactivator 1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. Afzelin also decreased the level of mitophagy‐related proteins, parkin and PTEN‐induced putative kinase 1. Furthermore, while GalN/LPS significantly increased the level of fission‐related protein, dynamin‐related protein 1, and decreased the level of fusion‐related protein, mitofusin 2; these effects were attenuated by afzelin.
Conclusions and Implications
Our findings demonstrated that afzelin protects against GalN/LPS‐induced liver injury by enhancing mitochondrial biogenesis, suppressing excessive mitophagy and balancing mitochondrial dynamics.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Tumor-targeting strategies for nanoparticles have been predominantly based on optimization of physical properties or conjugation with biological ligands. However, their tumor-targeting abilities ...remain limited and insufficient. Furthermore, traditional biological binding molecules have intrinsic limitations originating from the limited amount of cellular receptors and the heterogeneity of tumor cells. Our two-step in vivo tumor-targeting strategy for nanoparticles is based on metabolic glycoengineering and click chemistry. First, an intravenous injection of precursor-loaded glycol chitosan nanoparticles generates azide groups on tumor tissue specifically by the enhanced permeation and retention (EPR) effect followed by metabolic glycoengineering. These ‘receptor-like’ chemical groups then enhance the tumor-targeting ability of drug-containing nanoparticles by copper-free click chemistry in vivo during a second intravenous injection. The advantage of this protocol over traditional binding molecules is that there are significantly more binding molecules on the surface of most tumor cells regardless of cell type. The subsequent enhanced tumor-targeting ability can significantly enhance the cancer therapeutic efficacy in animal studies.
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IJS, KILJ, NUK, PNG, UL, UM
Background and Purpose
Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli including inflammation and microbial infection. Genipin, an aglycon of ...geniposide found in gardenia fruit, is well known to have anti‐inflammatory, antibacterial and antioxidative properties. This study examined the protective mechanisms of genipin against sepsis, with particular focus on the autophagic signalling pathway.
Experimental Approach
Mice were subjected to sepsis by caecal ligation and puncture (CLP). Genipin (1, 2.5 and 5 mg·kg−1) or vehicle (saline) was injected i.v. immediately (0 h) after CLP, and chloroquine (60 mg·kg−1), an autophagy inhibitor, was injected i.p. 1 h before CLP. Blood and liver tissues were isolated 6 h after CLP.
Key Results
Genipin improved survival rate and decreased serum levels of aminotransferases and pro‐inflammatory cytokines after CLP; effects abolished by chloroquine. The liver expression of autophagy‐related protein (Atg)12‐Atg5 conjugate increased after CLP, and this increase was enhanced by genipin. CLP decreased Atg3 protein liver expression, and genipin attenuated this decrease. CLP impaired autophagic flux, as indicated by increased liver expression of microtubule‐associated protein‐1 light chain 3‐II and sequestosome‐1/p62 protein; this impaired autophagic flux was restored by genipin, and chloroquine abolished this effect. Genipin also attenuated the decreased expression of lysosome‐associated membrane protein‐2 and Rab7 protein and increased expression of calpain 1 protein induced by CLP in the liver.
Conclusions and Implications
Our findings suggest that genipin protects against septic injury by restoring impaired autophagic flux. Therefore, genipin might be a potential therapeutic agent for the treatment of sepsis.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Countervailing anti-inflammatory response and immunosuppression can cause death in late sepsis. Depletion and dysfunction of T cells are critical for developing sepsis-induced ...immunosuppression. Heme oxygenase-1 (HO-1) has a regulatory effect on differentiation and function of T cells and anti-inflammatory properties. We therefore investigated the immunosuppressive role of HO-1 in sepsis with a focus on its effects on helper T-cell (Th) differentiation and regulatory T cells (Treg). Methods. Sepsis was induced by cecal ligation and puncture (CLP). Mice were intraperitoneally injected with zinc protoporphyrin (ZnPP; 25 mg/kg), an HO-1 inhibitor, or hemin (20 mg/kg), an HO-1 inducer, at 24 and 36 hours post-CLP. Splenocytes were isolated 48 hours post-CLP. Mice were intranasally infected with Pseudomonas aeruginosa 4 days post-CLP as a secondary pneumonia infection model. Results. ZnPP improved survival and bacterial clearance, whereas hemin had the opposite effect in septic mice. CLP induced lymphocyte apoptosis and a proinflammatory Th1 to anti-inflammatory Th2 shift, which was attenuated by ZnPP. ZnPP attenuated the CLP-induced Treg population and protein expression of inhibitory costimulatory molecules. Furthermore, ZnPP improved survival in the secondary pneumonia infection model. Conclusions. Our findings suggest that HO-1 overexpression contributes to sepsis-induced immunosuppression during late phase sepsis by promoting Th2 polarization and Treg function.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Response to digital healthcare lifestyle modifications is highly divergent. This study aimed to examine the association between single nucleotide polymorphism (SNP) genotypes and clinical efficacy of ...a digital healthcare lifestyle modification. We genotyped 97 obesity-related SNPs from 45 participants aged 18-39 years, who underwent lifestyle modification via digital cognitive behavioral therapy for obesity for 8 weeks. Anthropometric, eating behavior phenotypes, and psychological measures were analyzed before and after the intervention to identify their clinical efficacy. CETP (rs9939224) SNP significantly predict "super-responders" with greater body mass index (BMI) reduction (p = 0.028; GG - 2.91%, GT - 9.94%), while APOA2 (rs5082) appeared to have some potential for predicting "poor-responders" with lower BMI reduction (p = 0.005; AA - 6.17%, AG + 2.05%, and GG + 5.11%). These SNPs was also associated with significant differences in eating behavior changes, healthy diet proportions, health diet diversity, emotional and restrained eating behavior changes. Furthermore, classification using gene-gene interactions between rs9939224 and rs5082 significantly predicted the best response, with a greater decrease in BMI (p = 0.038; - 11.45% for the best response group (CEPT GT/TT × APOA2 AA) vs. + 2.62% for the worst response group (CEPT GG × APOA2 AG/GG)). CETP and APOA2 SNPs can be used as candidate markers to predict the efficacy of digital healthcare lifestyle modifications based on genotype-based precision medicine.Trial registration: NCT03465306, ClinicalTrials.gov. Registered March, 2018.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
As the global population ages, the prevalence of Parkinson's disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into ...dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer's disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The yellow coloring of the organic and inorganic pigments used in large Buddhist paintings during the late Joseon dynasty (17th–19th centuries) is herein analyzed using Raman spectroscopy and ...non‐invasive component analysis via p‐XRF. p‐XRF analyses of 194 yellow points on 12 large Buddhist paintings confirmed the use of gold, orpiment, and organic pigments; however, the yellow chromophoric elements of the organic pigments were not detected. The confirmed colors ranged from light yellow (close to white) to bright and dark yellow, but microscopic analysis revealed no particles or crystals. Accurate identification of pigments comprising light elements or organic compounds is challenging, which limits their identification via p‐XRF. In contrast, Raman spectroscopy of the samples presumed to be organic pigments detected gamboge in the samples, either alone, mixed with a white inorganic pigment such as lead white to express yellow, or overlaid upon such a pigment. These results demonstrate the utility of Raman spectroscopy in the analysis of organic pigments and provide a guide for the identification of coloring materials used in cultural heritage artifacts.
Complementary applications of p‐XRF and Raman spectroscopy were utilized to identify yellow pigments used in Korean Buddhist paintings. Pb in organic pigments was detected using p‐XRF, while Raman spectroscopy confirmed the presence of gamboge, which was generally mixed with or overlaid upon a white inorganic pigment such as lead white using different painting techniques.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall ...response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer.
In this open-label, single-arm, phase 2 trial, patients with recurrent or advanced, inoperable cervical cancer, who were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and histologically confirmed recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer, and who had progressed after available standard-of-care therapy were recruited from seven hospitals in South Korea. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, and 19, with one optional dose at week 46 that was at the investigator's discretion, and intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the overall response rate within 24 weeks assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 in patients who received at least 45 days of treatment 45 days of treatment with at least one post-baseline tumour assessment, and this is the report of a planned interim analysis. This trial is registered with ClinicalTrials.gov, NCT03444376.
Between June 19, 2018, and March 20, 2020, 36 patients were enrolled and received at least one dose of the study treatment. 26 patients were evaluable for interim activity assessment, with at least one post-baseline tumour assessment at week 10. At the data cutoff date on March 30, 2020, median follow-up duration was 6·2 months (IQR 3·5–8·1). At 24 weeks, 11 (42%; 95% CI 23-63) of 26 patients achieved an overall response; four (15%) had a complete response and seven (27%) had a partial response. 16 (44%) of 36 patients had treatment-related adverse events of any grade and four (11%) had grade 3–4 treatment-related adverse events. Grade 3 increased aspartate aminotransferase, syncope, pericardial effusion, and hyperkalaemia, and grade 4 increased alanine aminotransferase were reported in one patient each. No treatment-related deaths were reported.
Treatment with GX-188E therapeutic vaccine plus pembrolizumab for patients with recurrent or advanced cervical cancer was safe and treatment-related adverse events were manageable. This combination therapy showed preliminary antitumour activity in this interim analysis, which could represent a new potential treatment option for this patient population. This trial is ongoing.
National OncoVenture.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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