Advances in sarcopenia: mechanisms, therapeutic targets, and intervention strategies

Youle Zheng,Jin Feng,Yixin Yu,Min Ling,Xu Wang 대한약학회 2024 Archives of Pharmacal Research Vol.47 No.4

Sarcopenia is a multifactorial condition characterized by loss of muscle mass. It poses signifi cant health risks in older adultsworldwide. Both pharmacological and non-pharmacological approaches are reported to address this disease. Certain dietarypatterns, such as adequate energy intake and essential amino acids, have shown positive outcomes in preserving musclefunction. Various medications, including myostatin inhibitors, growth hormones, and activin type II receptor inhibitors, havebeen evaluated for their eff ectiveness in managing sarcopenia. However, it is important to consider the variable effi cacy andpotential side eff ects associated with these treatments. There are currently no drugs approved by the Food and Drug Administrationfor sarcopenia. The ongoing research aims to develop more eff ective strategies in the future. Our review of researchon disease mechanisms and drug development will be a valuable contribution to future research endeavors.

Anti-Inflammatory Effects of the 70 kDa Heat Shock Protein in Experimental Stroke

Zheng, Zhen,Kim, Jong Youl,Ma, Hualong,Lee, Jong Eun,Yenari, Midori A SAGE Publications 2008 Journal of cerebral blood flow and metabolism Vol.28 No.1

<P> The 70-kDa heat shock protein (Hsp70) is involved in protecting the brain from a variety of insults including stroke. Although the mechanism has been largely considered to be because of its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory responses. To explore how and whether Hsp70 regulate immune responses in brain ischemia, mice overexpressing Hsp70 (Hsp Tg) were subjected to 2 h middle cerebral artery occlusion, followed by 24 h reperfusion. Parallel experiments were performed using a brain inflammation model. Hsp Tg microglia cocultured with astrocytes were used to evaluate the direct effects of Hsp70 on cytotoxicity of mcrigolia. Compared with wild-type (Wt) littermates, Hsp Tg mice showed decreased infarct size and improved neurological deficits. The number of activated microglia/macrophages were also reduced in ischemic brains of Hsp Tg mice. Similar observations were made in a model of brain inflammation that does not result in brain cell death. Overexpression of Hsp70 in microglia completely prevented microglia-induced cytotoxicity to astrocytes. Activation of the inflammatory transcription factor, nuclear factor-κB (NF-κB) was inhibited significantly in Hsp Tg mice and microglia. This was associated with decreased phosphorylation of NF-κB inhibitor protein, IκBα, and decreased expression of several NFκB-regulated genes. Co-immunoprecipitation studies revealed an interaction of Hsp70 with NF-κB and IκBα, but not with IkB kinase, IKKγ, suggesting that Hsp70 binds to the NF-κB:IκB complex preventing IκB phosphorylation by IKK. The findings of the present work establish an anti-inflammatory role for Hsp70 in the context of brain ischemia as a novel mechanism of protection. </P>

70-kDa Heat Shock Protein Downregulates Dynamin in Experimental Stroke : A New Therapeutic Target?

Kim, Jong Youl,Kim, Nuri,Zheng, Zhen,Lee, Jong Eun,Yenari, Midori A. American Heart Association, Inc. 2016 Stroke Vol.47 No.8

<P>Background and Purpose-The 70-kDa heat shock protein (Hsp70) protects brain cells in models of cerebral ischemia. Proteomic screening of mice subjected to middle cerebral artery occlusion identified dynamin as a major downregulated protein in Hsp70-overexpressing mice (Hsp70 transgenic mice). Dynamin-1 is expressed in neurons and participates in neurotransmission, but also transports the death receptor Fas to the cell surface, where it can be bound by its ligand and lead to apoptosis. Methods-Mice were subjected to distal middle cerebral artery occlusion. Neuro-2a cells were subjected to oxygen glucose deprivation. Hsp70 transgenic and Hsp70-deficient (Hsp70 knockout) mice were compared with wild-type mice for histological and behavioral outcomes. Some mice and neuro-2a cell cultures were given dynasore, a dynamin inhibitor. Results-Hsp70 transgenic mice had better outcomes, whereas Hsp70 knockout mice had worse outcomes compared with wild-type mice. This correlated with decreased and increased dynamin expression, respectively. Dynamin colocalized to neurons and Fas, with higher Fas levels and increased caspase-8 expression. Hsp70 induction in neuro-2a cells was protected from oxygen glucose deprivation, while downregulating dynamin and Fas expression. Further, dynamin inhibition was found to be neuroprotective. Conclusions-Dynamin may facilitate Fas-mediated apoptotic death in the brain, and Hsp70 may protect by preventing this trafficking. Dynamin should be explored as a new therapeutic target for neuroprotection.</P>

ELSEVIER : C-Src-mediated phosphorylation of δ-catenin increases its protein stability and the ability of inducing nuclear distribution of β-catenin

( Yong Feng He ),( Hang Gun Kim ),( Tae Yong Ryu ),( Kwang Youl Lee ),( Won Seok Choi ),( Kyeong Man Kim ),( Mei Zheng ),( Yechan Joh ),( Jae Hyuk Lee ),( Dong Deuk Kwon ),( Qun Lu ),( Kwonseop Kim ) 전남대학교 약품개발연구소 2014 약품개발연구지 Vol.23 No.-

&-catenin was first considered as a brain spedfic protein, strong evidence of&-catenin overexpression in various cancers, including prostate cancer, has been accumulated. Phosphorylation of a-catenin by Akt and GSK313 has been studied in various cell lines. However, tyrosine phosphorylation of &-catenin in prostate cancer cells remains unknown. In the current study, we demonstrated that Src kinase itself phosphorylates &-catenin on its tyrosine residues in prostate cancer cells and further illustrated that Yl073, Yll12 and Yl176 of &-catenin are predominant sites responsible for tyrosine phosphorylation mediated by c-Src. Apart from c-Src, other Src family kinases, including Fgr, Fyn and Lyn, can also phosphorylate a-catenin. We also found that c-Src-mediated Tyr-phosphorylation of &-catenin increases its stability via decreasing its affinity to GSK313 and enhances its ability of indudng nuclear distribution of j3-catenin through interrupting the integrity of the E-cadherin. Taken together, these results indicate that c-Src can enhance the oncogenic function of&-catenin in prostate cancer cells. ⓒ 2013 Elsevier B.V. All rights reserved.

Three-dimensional Photogrammetric Mapping of Apples in Orchard based on Point Cloud Instance Segmentation

동슈아 ( Xuhua Dong ),김우영 ( Woo-young Kim ),정육 ( Zheng Yu ),오주열 ( Ju-youl Oh ),장제연 ( Je-yeon Jang ),이경환 ( Kyeong-hwan Lee ) 한국농업기계학회 2021 한국농업기계학회 학술발표논문집 Vol.26 No.2

The assessment of 3D fruit phenotyping traits of apple trees can provide management strategies for growers of apple orchards. The estimation of quantitative distribution of apples in orchard is an important parameter for yield estimation. Since it is hard to quantify them manually, resolving apple phenotyping efficiently is critical for monitoring apple yield and promoting a better management system. Thus in current study, we have developed a novel technology for 3D mapping of three types of apple training system fields. The 3D point cloud of apples was reconstructed using high spatial and temporal multi-viewing images collected by unmanned aerial vehicles (UAVs) based multi-camera system. The extraction of information about individual apple in 3D point cloud was executed using 3D instance segmentation algorithm which includes generalized sparse convolutional neural networks, discriminative loss function, and varying density-based 3D clustering method. The developed apple traits extraction algorithm could measure the 3D position of an individual apple by sphere fitting. The accuracy of the technique was evaluated by comparing its results with manual estimates of number of apples. The results obtained from our method are in good agreement with manual estimates. The average accuracy of apple counting in three types of the fields were ~92 % followed by the linear regression (R2) of 0.92 with root-mean-square error (RMSE) value of 13.93. Thus, 3D spatial distribution of apples were achieved and analyzed by above technique. This research proposes a method that combines 3D photography with 3D instance segmentation to accurately extract individual apples from various types of apple training systems in orchards and can also be used to segment and analyze other fruits.

Thirteen-Week Safety Evaluation on Meat Products of Somatic Cell-Cloned Cows in Rats

Young Min Cho,Ji-Soon Sin,Sun-Hee Kim,Hee-Youl Chai,Woon Kwon,Ehn-Kyoung Choi,Hu-Song Zhang,Zai-Zhi Huang,Mei-Shu Zheng,Hyeong-Jin Ji,Yong-Woo Roh,Yun-Bae Kim,Jong-Koo Kang 한국실험동물학회 2003 한국실험동물학회 학술발표대회 논문집 Vol.2003 No.-

Increase of isoflavones in soybean callus by Agrobacterium-mediated transformation

Jiang, Nan,Jeon, Eun-Hee,Pak, Jung-Hun,Ha, Tae-Joung,Baek, In-Youl,Jung, Woo-Suk,Lee, Jai-Heon,Kim, Doh-Hoon,Choi, Hong-Kyu,Cui, Zheng,Chung, Young-Soo The Korean Society of Plant Biotechnology 2010 Plant biotechnology reports Vol.4 No.4

Plant secondary metabolites have always been a focus of study due to their important roles in human medicine and nutrition. We transferred the isoflavone synthase (IFS) gene into soybean [Glycine max (L.) Merr.] using the Agrobacterium-mediated transformation method in an attempt to produce transformed soybean plants which produced increased levels of the secondary metabolite, isoflavone. Although the trial to produce transgenic plant failed due to unestablished hygromycin selection, transformed callus cell lines were obtained. The induction rate and degree of callus were similar among the three cultivars tested, but light illumination positively influenced the frequency of callus formation, resulting in a callus induction rate of 74% for Kwangan, 67% for Sojin, and 73% for Duyou. Following seven to eight subcultures on selection media, the isoflavone content of the transformed callus lines were analyzed by high-performance liquid chromatography. The total amount of isoflavone in the transformed callus cell lines was three- to sixfold higher than that in control callus or seeds. Given the many positive effects of isoflavone on human health, it may be possible to adapt our transformed callus lines for industrialization through an alternative cell culture system to produce high concentrations of isoflavones.

VDUP1 Is Required for the Development of Natural Killer Cells

Lee, Kee Nyung,Kang, Hyung-Sik,Jeon, Jun-Ho,Kim, Eun-Mi,Yoon, Suk-Ran,Song, Hyunkeun,Lyu, Chil-Youl,Piao, Zheng-Hao,Kim, Sun-Uk,Han, Ying-Hao,Song, Su-Sung,Lee, Young-Ho,Song, Kyu-Sang,Kim, Yong-Man,Y Elsevier 2005 Immunity Vol.22 No.2

<P><B>Summary</B></P><P>Vitamin D<SUB>3</SUB> upregulated protein 1 (VDUP1) is a stress-response gene that is upregulated by 1,25(OH)<SUB>2</SUB>D<SUB>3</SUB> in tumor cells. The in vivo roles of VDUP1 were investigated by producing mice lacking VDUP1 (VDUP1<SUP>−/−</SUP> mice). VDUP1<SUP>−/−</SUP> mice showed minimal changes in the development of T and B cells, but there was a profound reduction in the numbers of natural killer (NK) cells. As well, these mice showed decreased NK activity. In the VDUP1<SUP>−/−</SUP> mice, the expression of CD122 was reduced, demonstrating that VDUP1 is required for CD122 expression and NK maturation. In addition, severe lymphoid hyperplasia in the small intestine was observed in VDUP1<SUP>−/−</SUP> mice. Taken together, these results suggest that VDUP1 is a critical factor for the development and function of NK cells in vivo.</P>