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Lee Eunyoung,Park Sehee,Choi Jae-Phil,Kim Min-Kyung,Yang Eunmi,Ham Sin Young,Lee Seungjae,Lee Bora,Yang Jeong-Sun,Park Byoung Kwon,Kim Da Sol,Lee So-Young,Lee Joo-Yeon,Jang Hee-Chang,Jeon Jaehyun,Park 대한의학회 2023 Journal of Korean medical science Vol.38 No.8
Background: Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated. Methods: Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days. Results: A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P = 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively. Conclusions: Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.
Hesperidin Suppresses Melanosome Transport by Blocking the Interaction of Rab27A-Melanophilin
( Bora Kim ),( Jee Young Lee ),( Ha Yeon Lee ),( Ky Youb Nam ),( Jong Il Park ),( Su Min Lee ),( Jin Eun Kim ),( Joo Dong Lee ),( Jae Sung Hwang ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.5
We investigated the inhibitory effects of hesperidin on melanogenesis. To fi nd melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent.
Lee, Bora,Lee, Seunghee,Agulnick, Alan D.,Lee, Jae W.,Lee, Soo-Kyung The Company of Biologists Limited 2016 Development (Cambridge) Vol.143 No.10
<P>LIM homeodomain factors regulate the development of many cell types. However, transcriptional coactivators that mediate their developmental function remain poorly defined. To address these, we examined how two related NLI-dependent LIM complexes, which govern the development of spinal motor neurons and V2a interneurons, activate the transcription in the embryonic spinal cord. We found that single-stranded DNA-binding proteins are recruited to these LIM complexes via NLI, and enhance their transcriptional activation potential. Ssdp1 and Ssdp2 (Ssdp1/2) are highly expressed in the neural tube and promote motor neuron differentiation in the embryonic spinal cord and P19 stem cells. Inhibition of Ssdp1/2 activity in mouse and chick embryos suppresses the generation of motor neurons and V2a interneurons. Furthermore, Ssdp1/2 recruit histone-modifying enzymes to the motor neuron-specifying LIM complex and trigger acetylation and lysine 4 trimethylation of histone H3, which are well-established chromatin marks for active transcription. Our results suggest that Ssdp1/2 function as crucial transcriptional coactivators for LIM complexes to specify spinal neuronal identities during development.</P>
Lee, Mi-Ni,Lee, Shi-Nai,Kim, Se-Hee,Kim, Bora,Jung, Bo-Kyung,Seo, Ji Hae,Park, Ji-Hyeon,Choi, Jae-Hoon,Yim, Sun Hee,Lee, Mi-Ran,Park, Jong-Gil,Yoo, Ji-Young,Kim, Jeong Hun,Lee, Seung-Taek,Kim, Hwan-Mo Oxford University Press 2010 Journal of the National Cancer Institute Vol.102 No.6
<P><B>Background</B></P><P>Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A<SUP>225</SUP>) acetylates HIF-1α, triggering its degradation, and thus may play a role in decreased expression of VEGFA.</P><P><B>Methods</B></P><P>We generated Apc<SUP>Min/+</SUP>/mARD1A<SUP>225</SUP> transgenic mice and quantified growth of intestinal polyps. Human gastric MKN74 and murine melanoma B16F10 cells overexpressing mARD1A<SUP>225</SUP> were injected into mice, and tumor growth and metastasis were measured. VEGFA expression and microvessel density in tumors were assessed using immunohistochemistry. To evaluate the role of mARD1A<SUP>225</SUP> acetylation of Lys532 in HIF-1α, we injected B16F10-mARD1A<SUP>225</SUP> cell lines stably expressing mutant HIF-1α/K532R into mice and measured metastasis. All statistical tests were two-sided, and <I>P</I> values less than .05 were considered statistically significant.</P><P><B>Results</B></P><P>Apc<SUP>Min/+</SUP>/mARD1A<SUP>225</SUP> transgenic mice (n = 25) had statistically significantly fewer intestinal polyps than Apc<SUP>Min/+</SUP> mice (n = 21) (number of intestinal polyps per mouse: Apc<SUP>Min/+</SUP> mice vs Apc<SUP>Min/+</SUP>/mARD1A<SUP>225</SUP> transgenic mice, mean = 83.4 vs 38.0 polyps, difference = 45.4 polyps, 95% confidence interval [CI] = 41.8 to 48.6; <I>P</I> < .001). The growth and metastases of transplanted tumors were also statistically significantly reduced in mice injected with mARD1A<SUP>225</SUP>-overexpressing cells than in mice injected with control cells (<I>P</I> < .01). Moreover, overexpression of mARD1A<SUP>225</SUP> decreased VEGFA expression and microvessel density in tumor xenografts (<I>P</I> < .04) and Apc<SUP>Min/+</SUP> intestinal polyps (<I>P</I> = .001). Mutation of lysine 532 of HIF-1α in B16F10-mARD1A<SUP>225</SUP> cells prevented HIF-1α degradation and inhibited the antimetastatic effect of mARD1A<SUP>225</SUP> (<I>P</I> < .001).</P><P><B>Conclusion</B></P><P>mARD1A<SUP>225</SUP> may be a novel upstream target that blocks VEGFA expression and tumor-related angiogenesis.</P>
Lee, Jae Min,Lee, Jae Hyung,Kim, Eun Sun,Lee, Jung Min,Yoo, In Kyung,Kim, Seung Han,Choi, Hyuk Soon,Keum, Bora,Seo, Yeon Seok,Jeen, Yoon Tae,Lee, Hong Sik,Chun, Hoon Jai,Um, Soon Ho,Kim, Chang Duck Wolters Kluwer Health 2017 Medicine Vol.96 No.51
<P><B>Abstract</B></P><P>The safety of bowel-cleansing agents is an important issue in clinical practice, especially in patients with chronic diseases. Although the safety and efficacy of polyethylene glycol (PEG) has been investigated in many studies, few studies on PEG plus ascorbic acid exist. In this study, we compared the safety of 2 bowel-cleansing agents for patients with liver cirrhosis: 2-liter PEG (2 L PEG) plus ascorbic acid versus 4-liter PEG (4 L PEG). We performed a retrospective study on colonoscopy in patients with liver cirrhosis. Patients referred for colonoscopy were divided into 2 groups: 2 L PEG plus ascorbic acid (n = 105) and 4 L PEG (n = 61). Safety was assessed by comparing the clinical factors and laboratory findings as follows: blood biochemistry, electrolytes, weight change, and bowel-cleansing quality. Serum electrolytes, laboratory findings, and body weight showed no significant change between the 2 groups. There was no significant change in clinical factors before and after bowel preparation in the PEG group or the PEG plus ascorbic acid group. The acceptability and compliance of patients was better in the 2 L PEG plus ascorbic acid than the 4 L PEG group. In subgroup analysis, patients with compensated or decompensated cirrhosis showed no increased risk of electrolyte imbalances after bowel preparation. Child–Pugh scores did not influence the outcome after bowel cleansing. Successful cleansing was mostly achieved in both groups. Our analysis showed that of the use of 2 L PEG plus ascorbic acid could be a safe choice for colonoscopy in patients with liver cirrhosis.</P>
Brain-Specific Homeobox Factor as a Target Selector for Glucocorticoid Receptor in Energy Balance
Lee, Bora,Kim, Sun-Gyun,Kim, Juhee,Choi, Kwan Yong,Lee, Seunghee,Lee, Soo-Kyung,Lee, Jae W. American Society for Microbiology 2013 Molecular and cellular biology Vol.33 No.14
<P>The molecular basis underlying the physiologically well-defined orexigenic function of glucocorticoid (Gc) is unclear. Brain-specific homeobox factor (Bsx) is a positive regulator of the orexigenic neuropeptide, agouti-related peptide (AgRP), in AgRP neurons of the hypothalamic arcuate nucleus. Here, we show that in response to fasting-elevated Gc levels, Gc receptor (GR) and Bsx synergize to direct activation of <I>AgRP</I> transcription. This synergy is dictated by unique sequence features in a novel Gc response element in <I>AgRP</I> (AgRP-GRE). In contrast to AgRP-GRE, Bsx suppresses transactivation directed by many conventional GREs, functioning as a gene context-dependent modulator of GR actions or a target selector for GR. Consistent with this finding, AgRP-GRE drives fasting-dependent activation of a target gene specifically in GR<SUP>+</SUP> Bsx<SUP>+</SUP> AgRP neurons. These results define <I>AgRP</I> as a common orexigenic target gene of GR and Bsx and provide an opportunity to identify their additional common targets, facilitating our understanding of the molecular basis underlying the orexigenic activity of Gc and Bsx.</P>