• Title/Summary/Keyword: Molecular medicine

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Ginsenoside Rh2 reduces depression in offspring of mice with maternal toxoplasma infection during pregnancy by inhibiting microglial activation via the HMGB1/TLR4/NF-κB signaling pathway

  • Xu, Xiang;Lu, Yu-Nan;Cheng, Jia-Hui;Lan, Hui-Wen;Lu, Jing-Mei;Jin, Guang-Nan;Xu, Guang-Hua;Jin, Cheng-Hua;Ma, Juan;Piao, Hu-Nan;Jin, Xuejun;Piao, Lian-Xun
    • Journal of Ginseng Research
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    • v.46 no.1
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    • pp.62-70
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    • 2022
  • Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

Isolated Splenic Metastasis of Sigmoid Colon Cancer Detected by $^{18}F-FDG$ PET/CT ($^{18}F-FDG$ PET/CT 에서 발견된 S상 결장암의 단일 비장 전이)

  • An, Young-Sil;Yoon, Joon-Kee;Hong, Seon-Pyo;Choi, Bong-Hoi;Joh, Chul-Woo;Yoon, Seok-Nam
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.3
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    • pp.263-264
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    • 2007
  • Splenic metastasis from colon carcinoma are rare and usually occur in the presence of disseminated visceral metastasis. The liver is the most common site of metastatic spread from colon cancer. Several hypotheses have attempted to explain the low incidence of splenic metastasis. It should be difficult for colorectal cancer cells to reach the spleen through the portal venous system, in which the blood flow is usually from the spleen to the liver. Reticuloendothelial system or rhythmic contraction of the spleen may squeeze out the tumor in the spleen. The absence of afferent lymphatic to the spleen, phagocytic activity and humoral anticancer substances are considered to be other reason for low incidence of splenic metastasis. We report the case of $^{18}F-FDG$ PET/CT finding in a 70-year-old woman who develop isolated splenic metastasis of sigmoid colon cancer.

Molecular Types and Neoadjuvant Chemotherapy in Patients with Breast Cancer- While Molecular Shifting is More Common in Luminal a Tumors, The Pathologic Complete Response is Most Frequently Observed in Her-2 Like Tumors

  • Salim, Derya Kivrak;Mutlu, Hasan;Eryilmaz, Melek Karakurt;Musri, Fatma Yalcin;Tural, Deniz;Gunduz, Seyda;Coskun, Hasan Senol
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9379-9383
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    • 2014
  • Background: Pathologic complete response (pCR) is one of the most important target end-points of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigate the relationship between molecular subtypes and NACT in patients with BC. Materials and Methods: Using the Akdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectively identified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes, molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. Results: The distribution of subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillary were 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018). Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breast and axillary was significantly higher in patients with HER2-like type BC. Conclusions: In patients with HER-2 like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatment schedule should be reviewed again, especially in the luminal A group.

P53 transcription-independent activity mediates selenite-induced acute promyelocytic leukemia NB4 cell apoptosis

  • Guan, Liying;Huang, Fang;Li, Zhushi;Han, Bingshe;Jiang, Qian;Ren, Yun;Yang, Yang;Xu, Caimin
    • BMB Reports
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    • v.41 no.10
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    • pp.745-750
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    • 2008
  • Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. We have previously shown that sodium selenite can induce apoptosis by activating the mitochondrial apoptosis pathway in NB4 cells. However, the detailed mechanism remains unclear. Presently, we demonstrate that p53 contributes to apoptosis by directing signaling at the mitochondria. Immunofluorescent and Western blot procedures revealed selenite-induced p53 translocation to mitochondria. Inhibition of p53 blocked accumulation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, suggesting that mitochondrial p53 acts as an upstream signal of ROS and activates the mitochondrial apoptosis pathway. Selenite also disrupted cellular calcium ion homeostasis in a ROS-dependent manner and increased mitochondrial calcium ion concentration. p38 kinase mediated phosphorylation and mitochondrial translocation of p53. Taken together, these results indicate that p53 involves selenite-induced NB4 cell apoptosis by translocation to mitochondria and activation mitochondrial apoptosis pathway in a transcription-independent manner.

Isolation of feline panleukopenia virus from Yanji of China and molecular epidemiology from 2021 to 2022

  • Haowen Xue;Chunyi Hu;Haoyuan Ma;Yanhao Song;Kunru Zhu;Jingfeng Fu;Biying Mu;Xu Gao
    • Journal of Veterinary Science
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    • v.24 no.2
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    • pp.29.1-29.12
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    • 2023
  • Background: Feline panleukopenia virus (FPV) is a widespread and highly infectious pathogen in cats with a high mortality rate. Although Yanji has a developed cat breeding industry, the variation of FPV locally is still unclear. Objectives: This study aimed to isolate and investigate the epidemiology of FPV in Yanji between 2021 and 2022. Methods: A strain of FPV was isolated from F81 cells. Cats suspected of FPV infection (n = 80) between 2021 and 2022 from Yanji were enrolled in this study. The capsid protein 2 (VP2) of FPV was amplified. It was cloned into the pMD-19T vector and transformed into a competent Escherichia coli strain. The positive colonies were analyzed via VP2 Sanger sequencing. A phylogenetic analysis based on a VP2 coding sequence was performed to identify the genetic relationships between the strains. Results: An FPV strain named YBYJ-1 was successfully isolated. The virus diameter was approximately 20-24 nm, 50% tissue culture infectious dose = 1 × 10-4.94/mL, which caused cytopathic effect in F81 cells. The epidemiological survey from 2021 to 2022 showed that 27 of the 80 samples were FPV-positive. Additionally, three strains positive for CPV-2c were unexpectedly found. Phylogenetic analysis showed that most of the 27 FPV strains belonged to the same group, and no mutations were found in the critical amino acids. Conclusions: A local FPV strain named YBYJ-1 was successfully isolated. There was no critical mutation in FPV in Yanji, but some cases with CPV-2c infected cats were identified.