Young Hwa Kim’s research while affiliated with Ajou University Medical Center and other places

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Publications (118)


Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release
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September 2024

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130 Reads

Journal of Cell Science

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Kyoung-Min Choi

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Hyejin Mun

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Je-Hyun Yoon

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNA (miRNA) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNA, the roles of other micro RNA-binding proteins (miRBPs) remain unclear in regulation of miRNA loading, dissociation from RISC, and extracellular release. In this study, we perform protein arrays to profile miRBPs and identify 118 RNA-binding proteins directly binding with miRNAs. Among those proteins, RBP quaking (QKI) inhibits extracellular release of mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as hnRNPD/AUF1 and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates the Toll-like Receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in mouse cortex. Thus, this study reveals contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release.



Characteristics of young, mid-old, and old cells in vitro
a mRNA (left panel) and protein (right panel) levels of representative senescence markers (p53, p21Waf1, and p16INK4A) in young, mid-old, and old cells are shown. b Relative distances represented as VST using count data from young, mid-old, and old samples are shown (n = 2, each). c GSEA using the “FRIDMAN: senescence up” gene set in old vs. young (left panel), old vs. mid-old (middle panel), and mid-old vs. young cells (right panel) (adjp = 0.0029, 0.016, and 0.53, respectively). d NES calculated from GSEA using gene sets representing fibroblast functions are presented. The gene sets include “CYCLE” representing self-replicative ability, “ECM” representing ECM productive ability, “TISSUE” representing tissue regeneration ability, and “INFLAM” representing inflammation-regulating ability. Used gene sets and related statistics for this analysis can be found in Supplementary Data 2. e, f GSEA of old vs. young, old vs. mid-old, and mid-old vs. young using the “HALLMARK: inflammatory response” gene set is shown (adjp = 0.0075, 0.0087 for (e), and 0.31 for (f), respectively). g GSEA of mid-old vs. young using the “REACTOME: interleukin 1 signaling pathway” gene set is shown (adjp = 0.018). h NES calculated from GSEA using gene sets representing the inflammatory pathway are shown. Used gene sets and related statistics in this analysis can be found in Supplementary Data 2. i The mRNA levels of multiple inflammatory pathways related genes and SAA1 protein level were analyzed by real time PCR and ELISA analysis. j A list of analyzed genes that act as anti-inflammatory chemokines and cytokines used in this study is shown (left panel). The mRNA levels of the listed genes are shown (middle panel). ELISA analysis of SLIT2 in young, mid-old, and old cells (right lower panel). k A schematic image illustrating the characteristics of young, mid-old, and old cells with representative gene expression. l GSEA using the “GOBP: nuclear transport” gene set in mid-old vs. young (left panel), old vs. young (middle panel) and old vs. mid-old (right panel) cells is shown (adjp =  0.085, 0.046, and 0.042, respectively). m The mRNA expression of nuclear transport-related genes in RNA-seq (upper panel). The figures in the box represent FPKM counts. S1-6 represents the subunits of the importin α. Real-time PCR results of nuclear transport-related genes are shown (lower panel). n Erk1/2 phosphorylation and nuclear translocation were analyzed after serum stimulation for 30 min (upper panel). Quantification of the number of cells with p-Erk1/2 nuclear translocation (lower left panel). p-Erk1/2 level was analyzed by western blot (lower right panel). o Investigation of p-Erk1/2 translocation dynamics. Schematic illustration of Erk1/2-KTR-mClover system and kinetic parameters (left upper and left lower). Young (n = 4), mid-old (n = 6), and old (n = 3) cells were assessed with the system, respectively. Three independent experiments were repeated. Representative images of Erk1/2-KTR-mClover translocation (right upper). Erk1/2-KTR-mClover translocation C/N curves for each cell type (middle). Cells were starved for 24 h with serum free media prior to experiments. Fluorescent images were acquired every 15 sec for 30 min after serum stimulation. Comparison of translocation kinetic parameters between cell types (lower panel). The p value in (a), (i), (j), and (m–o) was calculated using the one-tailed Mann–Whitney U-test. The p values in (c–h), and (i) are obtained using GSEA statistics in ‘fgsea’ package. ES enrichment score, NES normalized enrichment score, adjp = adjusted p value. The graph in (a), (i), (j), and (m–o) was represented as mean ± SD. A thousand times of permutations were performed for adjustment in (c–h) and (l).
Mid-old specific gene expression in old-aged tissues
a–d Representative images of p21Waf1, SAA1, IL1β and SLIT2 IHC analysis in young and old-aged human colon and lung tissues are shown. “1” and “2” indicate high-magnification views of the original figure. Image “1” primarily depicts the epithelium and smooth muscle region, while image “2” depicts a stromal-rich region. Black arrows indicate stained cells in the stromal region. Yellow arrow in (d) indicate SLIT2-positive cells in epithelial region. Corresponding quantification dot plots are shown in the right panel of each figure. IHC results were presented as the percentage of positive cells in the stromal or epithelial region. The p value was calculated using the one-tailed Mann–Whitney U-test. The graphs in (b) (right tables) and (d) (lower right table) were represented as mean + SD. The graphs in (a), (b) (left tables), (c), and (d) (left tables) were represented as mean ± SD.
The Effect of SAA1 on old-aged tissues
a Schematic drawing of the effect of SAA1 on tissue. b Young fibroblasts or c smooth muscle cells (PASMCs) were treated with rhSAA1 for 24 h and SASP expression was analyzed using real-time PCR (left panel). MMP9 protein expression was analyzed by ELISA (right panel). d Serially dissected human colon tissues were subjected to IHC analysis for SAA1 and MMP9. Corresponding quantification data is shown in the right panel. IHC results were presented as the percentage of positive cells in the stromal region. e PASMCs were treated with rhSAA1 at the indicated concentration for 24 h and real-time PCR was performed using primers for atrophy-related genes. f IHC analysis for SAA1 in colon tissue from young and elderly subjects, and muscular mucosa thickness was measured. g IHC analysis for type IV collagen of colon tissues from young and elderly subjects is shown. “1” and “2” indicate high-magnification views of the original figure (left panel). Each protein expression was presented as weak, moderate, and strong (right upper panel). mRNA expression level of COL4A1 and COL4A2 in fibroblasts/smooth muscle cells was analyzed between young and old subjects in scRNA-seq data set (GSE178341)³⁴ (right lower panel). hCOL4A1, COL4A2 and COL4A3 gene-expression were analyzed by real-time PCR in young, mid-old, and old fibroblasts (upper panel). Young fibroblasts were treated rhSAA1 for 24 h, and mRNA expression level of type IV collagen was analyzed (lower panel). i In vitro Matrigel degradation assay results are shown. Matrigel-coated membrane was co-cultured with young or mid-old fibroblasts for 2 days. Degradation of type IV collagen was analyzed using western blotting. Three independent experiments were performed to get similar results. j Cell morphology was analyzed using F-actin staining (left panel) and functional marker expression was measured using real-time PCR analysis (right panel) in HCoEpiC. k NHE3 immunostaining in human (upper panel) and mouse (lower panel) colon tissue. NHE3 was stained in the apical region of the colon epithelium. Each protein expression status indicates weak, moderate, and strong. The p values of figure (b–f), (g) (lower graph), (h), and (j) are obtained from the one-tailed Mann–Whitney U test. The p values of figure (g) (upper graph) and (k) are obtained from Chi-square test. The graph in (b–h), and (j) was represented as mean ± SD.
The Functional role of BM degradation in the lung tissue of the elderly
a IHC analysis of human lung tissues were subjected for MMP9. Quantification data of IHC results is shown in the right panel. b IHC analysis of Type IV collagen was performed on lung tissue obtained from elderly and young subjects. High-magnification views of the original figure are represented as “1” and “2”. c The schematic image illustrates the process of water exchange in the lung. Alveolar water absorption is regulated by the uptake of Na⁺ ions through the apical SCNN1A channel and the basolateral ATP1A pump in type II alveolar cells. d IMR90 lung fibroblasts were sub-cultured to generate mid-old cells (DT 4 days). The mRNA expression of mid-old cell markers in young and mid-old IMR90 cells is shown in the left panel. Young IMR90 cells were treated with rhSAA1 for 24 h, and the mRNA expression of IL1β and MMP9 was analyzed in the right panel. e HPAEpiC were treated with rhSAA1 (100 ng/ml) for 24 h, and the expression of SFTPD, AQP3, ATP1A1, and SCNN1A was analyzed using real-time PCR. f HPAEpiC were cultured on the Matrigel-coated membrane for 2 days, and the expression levels of ATP1A1 and SCNN1A were analyzed using real-time PCR. g IHC analysis of SCNN1A in human lung tissue is shown. Arrows indicate SCNN1A-expressing cells. Quantification data of IHC results is shown in the lower panel. h IHC analysis of SCNN1A in mouse lung tissue is shown. Arrows indicate SCNN1A-positive cells. Quantification data of IHC results is shown in the left lower panel. The mRNA expression level of SCNN1A was analyzed in the mouse lung tissue is shown (right lower panel). IHC results were presented as the percentage of positive cells in the stromal or epithelial region. The p values of (a), (d–g), and (h) are obtained from the one-tailed Mann–Whitney U test. The p value of (b) is obtained using Chi-square test. The graphs in (a) and d–h) were represented as mean ± SD.
Young cell-driven factors reverse the phenotype of mid-old cells
a A schematic drawing of the stromal cell population according to the aging process is shown. b Mid-old cells are co-cultured with young or mid-old cells for 30 days, respectively. IF staining for Ki67 was performed (left upper panel). Quantification data for Ki67 is shown in the right upper panel. The cell size was compared and quantified (left lower panel). After 30 days of co-culture, cell growth rates were measured over a period of 10 days (right lower panel). c EdU incorporation assay. Mid-old cells co-cultured with young or mid-old cells for 30 days and then analyzed EdU incorporation. Quantification data is shown in the lower panel. d GSEA was performed in mid-old cells co-cultured with young and mid-old cells, respectively (n = 2, each). Functional gene sets of fibroblasts including “CYCLE” representing self-replicative ability, “ECM” representing ECM productive ability, “TISSUE” representing tissue regeneration ability, and “INFLAM” representing inflammation-regulating ability were analyzed. Used gene sets and related statistics for this analysis can be found in Supplementary Data 2. e GSEA was performed for “GOBP: mitotic cell cycle”, “GOBP: DNA replication”, “GOMF: extracellular matrix structural constituent”, “GOBP: tissue migration”, and “Hallmark: inflammatory response” (adjp = 0.038, 0.038, 0.038, 0.038, and 0.11). The p value and adjp are obtained using GSEA statistics in ‘fgsea’ package. ES: enrichment score; NES: normalized enrichment score; adjp: adjusted p value. f The mRNA expression of inflammatory, anti-inflammatory genes, and ECM-related molecules in mid-old cells co-cultured with young or mid-old cells (upper panel). ELISA analysis of IL1β and SAA1 in mid-old cells co-cultured with young or mid-old cells (lower panel). g The expression level of Lnc-RNAs was measured using real-time PCR in young, mid-old, and old cells (upper panel). Lnc-RNAs were isolated from multiple cellular compartments and shown using conventional real time-PCR (lower panel). h Mid-old cells were infected with lentivirus harboring Lnc-SBLC for 4 days. Cell morphology (upper panel) was observed and p53 and p21Waf1 expression were analyzed using real-time PCR (left lower panel) and western blot analysis (right lower panel). i The upper panel shows the cell growth rate, which was measured by counting the cells every 4 days. The lower panel displays the expression levels of inflammatory genes, which were measured using real-time PCR. j Mid-old cells were infected with lentiviruses carrying sh-p21Waf1 for 4 days. Cell morphology was examined and depicted in the left panel, while the cell growth rate was monitored by counting the cells every 4 days (right upper panel). The expression of various inflammatory genes was assessed using real-time PCR (right lower panel). The p values of (b) (right upper and lower), (c), and (f), (j) are obtained from the one-tailed Mann–Whitney U test. The p value of (b) (left lower) is obtained from two-tailed Student’s t test. The p values of (e) (left lower) are obtained using GSEA statistics in ‘fgsea’ package in R. The graphs in (b), (c), and (f–j) were represented as mean ± SD. A thousand times of permutations were performed for GSEA adjustment.

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Mid-old cells are a potential target for anti-aging interventions in the elderly
  • Article
  • Full-text available

November 2023

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178 Reads

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4 Citations

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

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Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation

November 2023

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39 Reads

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3 Citations

Journal of Pathology and Translational Medicine

Background: Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells. Methods: Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model. Results: Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength. Conclusions: Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.


CDK4 /6 inhibitors induce breast cancer senescence with enhanced anti‐tumor immunogenic properties compared with DNA ‐damaging agents

October 2023

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36 Reads

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8 Citations

Molecular Oncology

Since therapy‐induced senescence (TIS) can either support or inhibit cancer progression, identifying which types of chemotherapeutic agents can produce the strongest anti‐tumor TIS is an important issue. Here, cyclin‐dependent kinase4/6 inhibitors (CDK4/6i)‐induced senescence was compared to the TIS induced by conventional DNA‐damaging agents. Despite both types of agents eliciting a similar degree of senescence, we observed increased expression of the senescence‐associated secretory phenotype (SASP) and ligands related to pro‐tumor immunity ( IL6 , CXCL8 , TGFβ , CD274 , CEACAM1 ) and angiogenesis ( VEGFA ) mainly in TIS induced by DNA‐damaging agents rather than by CDK4/6i. Additionally, although all agents increased the expression of anti‐tumor immunomodulatory proteins related to antigen presentation ( MHC‐I , B2M ) and T cell chemokines ( CXCL9 , 10 , 11 ), CDK4/6i‐induced senescent cells still maintained this expression at a similar or even higher intensity than cells treated with DNA‐damaging agents, despite the absence of nuclear factor‐kappa‐B (NF‐κB) and p53 activation. These data suggest that in contrast with DNA‐damaging agents, which augment the pro‐tumorigenic microenvironment via pro‐inflammatory SASP, CDK4/6i can generate TIS only with antitumor immunomodulatory proteins.


Fig. 2. p15 INK4B is an alternative marker for detection of STCs in CRC in vivo. (A) Clusters of EPCAM-positive cancer cells from patient #8 and feature plots of MKI67 and CDKN2A. (B) Dot plot showing the expression pattern of the senescence marker CDKN2A and the proliferation marker MKI67 in each cluster. (C) GSEA using a cellular senescence-related gene set. Leading edges which are upregulated in cluster 1 are shown in the box below. (D) Dot plot showing the expression pattern of CDKN2A and CDKN2B in each cluster. (E) IHC analysis using serial sections from p16 INK4A -positive FFPE CRC tissue. (F) IHC analysis using serial sections from p16 INK4A -negative FFPE CRC tissue. (G) Table showing correlations between p15 INK4B and p16 INK4A expression in FFPE IHC samples. The p value was calculated using Fisher's exact test.
Fig. 3. STC p15 INK4B expression in vitro. (A) SA-β-Gal staining in two cancer cell senescence models, H 2 O 2 -induced (60 μM) and doxorubicin (Dox)-induced (50 nM) senescence models (n = 4, each). The p values are obtained using Mann-Whitney U test. (B) DAPI staining revealed heterochromatin foci, in both H 2 O 2 -induced (60 μM) and doxorubicin (Dox)-induced (50 nM) senescence models. The proportion of SAHF-positive cells out of total cells was shown in the bar graph and p values were obtained from chi-square test. (C) mRNA expression of CDKN2A and CDKN2B in H 2 O 2 -induced (60 μM) and doxorubicin (Dox)-induced (50 nM) senescence models (n = 3, each). The p values were obtained using Student's t-test.
Patient characteristics according to their p16 INK4A expression in IHC analysis.
p15INK4B is an alternative marker of senescent tumor cells in colorectal cancer

February 2023

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79 Reads

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5 Citations

Heliyon

Senescent tumor cells are nonproliferating tumor cells which are closely related to cancer progression by secreting senescence-related molecules, called senescence-associated secreting phenotypes. Therefore, the presence of senescent tumor cells is considered a prognostic factor in various cancer types. Although senescence-associated β-galactosidase staining is considered the best marker for detection of senescent tumor cells, it can only be performed in fresh-frozen tissues. p16INK4A, a cyclin-dependent inhibitor, has been used as an alternative marker to detect senescent tumor cells in formalin-fixed paraffin-embedded tissues. However, other reliable markers to detect senescent tumor cells is still lacking. In the present study, using public single-cell RNA-sequencing data, we found that p15INK4B, a cyclin-dependent kinase inhibitor, is a novel marker for detection of senescent tumor cells. Moreover, p15INK4B expression was positively correlated with that of p16INK4A in colorectal cancer tissues. In in vitro studies, mRNA expression of p15INK4B was increased together with that of p16INK4A in H2O2- and therapy-induced cancer senescence models. However, the mRNA level of p15INK4B did not increase in the oncogene-induced senescence model in primary colonic epithelial cells. In conclusion, p15INK4B is a potential alternative marker for detection of senescent tumor cells together with conventional markers in advanced stages of colorectal cancer.



TMIC-14. DIFFUSE P16INK4A EXPRESSION IS ASSOCIATED WITH TUMOR CELL SENESCENCE AND SENESCENCE-ASSOCIATED SECRETARY PHENOTYPE RELATED TO IMMUNE MICROENVIRONMENT IN GLIOBLASTOMAS

November 2022

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10 Reads

Neuro-Oncology

Cellular senescence (CS) is a state of irreversible cell cycle arrest, and the expression of p16INK4a in cells is one of the reliable markers for CS. However, senescent cells are metabolically active with the senescence-associated secretory phenotype (SASP), which can influence the tissue microenvironment by paracrine signaling to the adjacent tumor, non-tumor, and immune cells. In the present study, we evaluated p16INK4a expression in glioblastoma and investigated its association with CS and SASPs. We analyzed the expression of p16INK4a in 73 glioblastomas by immunostaining. To examine the association of p16INK4a expression and CS, we performed senescence-associated β-galactosidase (SA-β-Gal) staining, a standard marker of CS, using glioblastoma cell lines and fresh frozen tumor tissues. For SASPs analysis, RNA sequencing with Gene Set Enrichment Analysis (GSEA) was performed. Among 73 glioblastomas, twenty-eight cases (38.4%) revealed diffuse strong p16INK4a expression in tumor cells. The glioblastoma with diffuse p16INK4a expression (GMDP) patients were younger (52.4 vs. 59.2 years) and showed prolonged overall survival (median: 25.5 vs. 12.3 months) compared to those harboring negative expression. In vitro analysis, p16INK4a over-expressed glioblastoma cell line showed increased expression of SA-β-Gal which indicates CS. In addition, fresh frozen tissues from GMDP also revealed SA-β-Gal positivity. RNA sequencing analysis revealed that splicing or protein biosynthetic genes were enriched in GMDP, and GSEA showed significant enrichment of SASP genes (false discovery rate < 0.05), especially chemokines associated with monocytes and macrophages. Our data suggest that increased expression of p16INK4a in glioblastoma is associated with tumor cell senescence, and SASPs from senescent tumor cells could be one of the crucial modulators in the tumor immune microenvironment.


The Elderly’s Organs are Ready for Functional Rejuvenation

September 2022

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61 Reads

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified that the numbers of full-senescent cells were not increased in normal elderly tissue. Instead, fibroblasts and smooth muscle cells that were neither proliferative nor fully senescent were prevalent in tissues of the elderly, which we termed “mid-old” cells. Upregulation of pro-inflammatory genes (IL1β, SAA1) and downregulation of anti-inflammatory genes (SLIT2, CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Strikingly, the microenvironmental change and the functional decline of mid-old cells could be rejuvenated by a young cell-originated protein, SLIT2. We provided the functional reverse of mid-old cells rather than elimination of senescent cells as a new concept about rejuvenation.


Anti-fatigue potential of Pinus koraiensis leaf extract in an acute exercise-treated mouse model

September 2022

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24 Reads

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14 Citations

Biomedicine & Pharmacotherapy

Pinus koraiensis leaf (PKL) extract exerts antihyperlipidemic, antidiabetic, and anticancer effects; however, its anti-fatigue properties have not been elucidated to date. In this study, the anti-fatigue properties of PKL were evaluated by assessing the endurance of mice by a weight-loaded forced swimming (WLFS) and rotarod (RR) tests. Subsequently, various behavioral, biochemical, and physiological parameters were measured. Treatment with PKL decreased hepatic and muscular glycogen levels in mice subjected to WLFS and RR test compared to those in acute exercise-treated (AET) mice. Additionally, plasma levels of stress-related biochemical factors (lactate, lactate dehydrogenase, aminotransferase, aspartate aminotransferase, and blood urea nitrogen) decreased significantly (P < 0.05), whereas the levels of superoxide dismutase and glutathione peroxidase increased. Furthermore, PKL potentially improved mental fatigue by decreasing corticosterone and increasing serotonin levels. PKL increased the expression of phosphorylated cyclic adenosine-3′,5′-monophosphate response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Collectively, the anti-fatigue effects of PKL could be explained by its antioxidant activity, mediating effects on glycogen synthesis, and control over stress. In conclusion, the findings of the present study suggest that PKL is a potential nutraceutical for improving exercise performance and alleviating fatigue.


Citations (56)


... Cellular senescence is commonly recognized as a tumor-suppressing mechanism; however, senescent cells also exhibit heightened invasiveness and lymphangiogenic capabilities attributed to the development of a senescence-associated secretory phenotype [34]. Recent studies report that cellular senescence is associated with the spatial evolution of colorectal cancer toward a more metastatic phenotype [35]. Oxidative stress plays a crucial role in promoting various aggressive behaviors in tumors. ...

Reference:

Identification of metastasis-related genes for predicting prostate cancer diagnosis, metastasis and immunotherapy drug candidates using machine learning approaches
Cellular senescence is associated with the spatial evolution toward a higher metastatic phenotype in colorectal cancer
  • Citing Article
  • March 2024

Cell Reports

... Complications in complex II can also lead to cancer, cell death, and necrosis [24,25]. Although mitochondrial complexes I and II differ in their roles within the electron transport chain, as well as in the occurrence of diseases resulting from dysfunction in each complex, mitochondrial functional studies utilize analyses of total ATP level or indirect measurement data, such as oxygen consumption and mitochondrial complex enzyme activity [26,27]. ...

Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation

Journal of Pathology and Translational Medicine

... Moreover, SnCs induced by either DNA damage agents or CDK4/6 inhibitors express antigen presentation machinery that potentiates T cell responses [210]. Similarly, SnCs induced by Abemaciclib demonstrate increased surface levels of β2M and present tumor antigens to the T cell receptor (TCR) of cytotoxic CD8 + T cells, thereby eliciting T cell dependent anti-tumor responses [211]. ...

CDK4 /6 inhibitors induce breast cancer senescence with enhanced anti‐tumor immunogenic properties compared with DNA ‐damaging agents
  • Citing Article
  • October 2023

Molecular Oncology

... Therefore, a key indicator of exercise fatigue is the severe consumption of energy reserves such as HG and MG [15,16] . Previous studies have shown that ethanol extract of Moringa oleifera leaves [14] , apple pomace polysaccharide [15] , lemon seed flavonoids [17] , Pinus koraiensis leaf extract [18] , and fermented soybean protein peptide [19] can enhance glycogen levels and exhibit antifatigue effects. The low glycogen level of the model group (Fig. 3) suggests that exhaustive loaded swimming could reduce reserves of both HG and MG, resulting in acute exercise fatigue, which is consistent with previous reports [14][15][16][17][18][19] . ...

Anti-fatigue potential of Pinus koraiensis leaf extract in an acute exercise-treated mouse model
  • Citing Article
  • September 2022

Biomedicine & Pharmacotherapy

... Existing studies have also explored the relationship between the inhibitory cytokine MCSF and tumor immunity. Senescent tumor cells, for instance, secrete MCSF to drive macrophage polarization toward the M2 subtype and inhibit CD8 + T cell activation [43]. Additionally, RT can stimulate the tyrosine kinase ABL1 in prostate cancer cells, leading to its translocation from the cytoplasm to the nucleus where it binds to the MCSF gene promoter, thus promoting MCSF secretion from prostate cancer cells [44]. ...

Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer

... Transient receptor potential (TRP) V4 in non-myelinating SCs has been associated with demyelination following nerve injuries in mice, with functional TRPV4 expression confirmed in cultured mouse SCs [6]. TRPM7 in mouse SCs has been shown to play a role in peripheral neurodegenerative processes in ex vivo sciatic nerve cultures [7,8]. Additionally, functional TRPA1 expression has been identified in mouse primary SCs, and its involvement in allodynia has been demonstrated, including in cultured rat and human SCs [9,10]. ...

Inhibition of transient receptor potential melastatin 7 (TRPM7) protects against Schwann cell trans-dedifferentiation and proliferation during Wallerian degeneration

... Transient receptor potential (TRP) V4 in non-myelinating SCs has been associated with demyelination following nerve injuries in mice, with functional TRPV4 expression confirmed in cultured mouse SCs [6]. TRPM7 in mouse SCs has been shown to play a role in peripheral neurodegenerative processes in ex vivo sciatic nerve cultures [7,8]. Additionally, functional TRPA1 expression has been identified in mouse primary SCs, and its involvement in allodynia has been demonstrated, including in cultured rat and human SCs [9,10]. ...

Carvacrol effectively protects demyelination by suppressing transient receptor potential melastatin 7 (TRPM7) in Schwann cells
  • Citing Article
  • December 2019

Anatomical Science International

... As the MFM device does not modify intra-aneurysmal pressure, branch perfusion is maintained. This result is in agreement with animal [32], in vivo [2,9,11,16,18,22] and in silico [26,31] reports of branch flow perfusion preservation after MFM deployment. ...

Multilayer Flow Modulator (MFM) Stent Insertion at Saccular Aneurysm in Peri-visceral Aorta: A Case Report.
  • Citing Article
  • December 2019

European Journal of Vascular and Endovascular Surgery

... A dietary shift from gestation to lactation feed during the transition phase is essential to meet the heightened energy and protein needs associated with the foetus's rapid development in the latter stages of gestation. Interestingly, Choi et al. (2019) noted that sows under heat stress require more metabolic energy, thus requiring increased feed intake. In Thailand, pig barns that are equipped with evaporative cooling systems report average temperatures of 21.7°C during cooler seasons and 25.8°C in hotter seasons (Tummaruk et al., 2023). ...

Additional feeding during late gestation improves initial litter weight of lactating sows exposed to high ambient temperature

Revista Brasileira de Zootecnia

... The number of kidney transplants has been increasing since the 1980s. In past eras, most kidney transplant programs were based on living donations, and the deceased donor kidney transplant program operated in some centers 1 . After the introduction of brain death legislation and the establishment of regulatory agencies, deceased donor kidney transplant programs showed a decline in the early 2000s. ...

A Half-Century 3000 Cases of Kidney Transplant Experiences in a Single Hospital: the Longest Registry in Korea

Transplantation Proceedings