• Title/Summary/Keyword: Metabolic Targeting

Search Result 75, Processing Time 0.027 seconds

Parenting Stress and Guilty Feeling for Mothers Having Children with Rare Genetic Metabolic Diseases (희귀유전대사질환 아동 어머니의 양육 스트레스와 죄책감)

  • Kwon, Eun Kyung;Choi, Mi Hye;Kim, Su Kang
    • Journal of Korean Clinical Nursing Research
    • /
    • v.14 no.3
    • /
    • pp.153-163
    • /
    • 2008
  • Purpose: The purpose of this research, using descriptive correlation design was to identify the extent to which the mothers having children with rare genetic metabolic diseases(MPS, PWS) have parenting stress and guilt feeling. Method: This study used PSI /SF(Abidin, 1995) and Guilt Index as devised herein. From 156 mothers, data were collected from February to July 2006, using self-administered questionnaires. This study received the approval from IRB at S Hospital (IRB File No: 2006-02-014). Data were analyzed with descriptive statistics, t-test, ANOVA, and correlation. Results: Mothers felt very high level of parenting stress and sense of guilt. Parenting stress was related positively to guilt feeling. Conclusion: These findings could help understand the families of children with rare genetic metabolic diseases and those provide basic information in developing effective counseling and education programs for relief of parenting stress and guilt feeling. This study would be significant in the fact that it is the first research, targeting on the families of children with rare genetic metabolic diseases in Korea.

  • PDF

Current status of CRISPR/Cas9 base editor technologies and their applications in crop precision breeding

  • Kim, Rigyeong;Song, Jaeeun;Ga, Eunji;Min, Myung Ki;Lee, Jong-Yeol;Lim, Sun-Hyung;Kim, Beom-Gi
    • Korean Journal of Agricultural Science
    • /
    • v.46 no.4
    • /
    • pp.885-895
    • /
    • 2019
  • Plant biotechnologists have long dreamed of technologies to manipulate genes in plants at will. This dream has come true partly through the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology, which now has been used to edit genes in several important crops. However, there are many restrictions in editing a gene precisely using the CRISPR/Cas9 technology because CRISPR/Cas9 may cause deletions or additions in some regions of the target gene. Several other technologies have been developed for gene targeting and precision editing. Among these, base editors might be the most practically and efficiently used compared to others. Base editors are tools which are able to cause a transition from cytosine into thymine, or from adenine into guanine very precisely on specific sequences. Cytosine base editors basically consist of nCas9, cytosine deaminase, and uracil DNA glycosylase inhibitor (UGI). Adenine base editors consist of nCas9 and adenine deaminase. These were first developed for human cells and have since also been applied successfully to crops. Base editors have been successfully applied for productivity improvement, fortification and herbicide resistance of crops. Thus, base editor technologies start to open a new era for precision gene editing or breeding in crops and might result in revolutionary changes in crop breeding and biotechnology.

Metabolic Signaling by Adipose Tissue Hormones in Obesity (비만에서 adipose tissue 호르몬에 의한 metabolic signaling)

  • Younghoon Jang
    • Journal of Life Science
    • /
    • v.33 no.3
    • /
    • pp.287-294
    • /
    • 2023
  • Healthy adipose tissue is critical for preventing obesity by maintaining metabolic homeostasis. Adipose tissue plays an important role in energy homeostasis through glucose and lipid metabolism. Depending on nutritional status, adipose tissue expands to store lipids or can be consumed by lipolysis. The role of adipose tissue as an endocrine organ is emerging, and many studies have reported that there are various adipose tissue hormones that communicate with other organs and tissues through metabolic signaling. For example, leptin, a representative peptide hormone secreted from adipose tissues (adipokine), circulates and targets the central nervous system of the brain for appetite regression. Furthermore, adipocytes secrete inflammatory cytokines to target immune cells in adipose tissues. Not surprisingly, adipocytes can secrete fatty acid-derived hormones (lipokine) that bind to their specific receptors for paracrine and endocrine action. To understand organ crosstalk by adipose tissue hor- mones, specific metabolic signaling in adipocytes and other communicating cells should be defined. The dysfunction of metabolic signaling in adipocytes occurs in unhealthy adipose tissue in overweight and obese conditions. Therapy targeting novel adipose metabolic signaling could potentially lead to the development of an effective anti-obesity drug. This review summarizes the latest updates on adipose tissue hormone and metabolic signaling in terms of obesity and metabolic diseases.

Targeting Glutamine Metabolism for Cancer Treatment

  • Choi, Yeon-Kyung;Park, Keun-Gyu
    • Biomolecules & Therapeutics
    • /
    • v.26 no.1
    • /
    • pp.19-28
    • /
    • 2018
  • Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling. Furthermore, we summarize the potential therapeutic approaches of targeting glutamine metabolism for the treatment of numerous types of cancer.

Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits

  • Wang, Jie;Zhang, Li;Wang, Lijuan;Liu, Zhonghong;Yu, Yu
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.21 no.1
    • /
    • pp.45-54
    • /
    • 2017
  • Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultra-performance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite $M_{un}$ differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of $M_{un}$ may further suggest an alternative species-specific metabolic pathway.

Metabolic perturbation of an Hsp90 C-domain inhibitor in a lung cancer cell line, A549 studied by NMR-based chemometric analysis

  • Hur, Su-Jung;Lee, Hye-Won;Shin, Ai-Hyang;Park, Sung Jean
    • Journal of the Korean Magnetic Resonance Society
    • /
    • v.18 no.1
    • /
    • pp.10-14
    • /
    • 2014
  • Hsp90 is a good drug target molecule that is involved in regulating various signaling pathway in normal cell and the role of Hsp90 is highly emphasized especially in cancer cells. Thus, much efforts for discovery and development of Hsp90 inhibitor have been continued and a few Hsp90 inhibitors targeting the N-terminal ATP binding site are being tested in the clinical trials. There are no metabolic signature molecules that can be used to evaluate the effect of Hsp90 inhibition. We previously found a potential C-domain binder named PPC1 that is a synthetic small molecule. Here we report the metabolomics study to find signature metabolites upon treatment of PPC1 compound in lung cancer cell line, A549 and discuss the potentiality of metabolomic approach for evaluation of hit compounds.

Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development

  • Yujin Jin;Kyung-Sun Heo
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.27 no.4
    • /
    • pp.299-310
    • /
    • 2023
  • Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.

1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation

  • Hyoeun Jeon;Jungeun Yu;Jung Me Hwang;Hye-Won Park;Jiyeon Yu;Zee-Won Lee;Taesoo Kim;Jaerang Rho
    • IMMUNE NETWORK
    • /
    • v.22 no.5
    • /
    • pp.43.1-43.12
    • /
    • 2022
  • Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

Treatment strategies targeting specific genetic etiologies in epilepsy

  • Kim, Hyo Jeong;Kang, Hoon-Chul
    • Journal of Genetic Medicine
    • /
    • v.18 no.1
    • /
    • pp.8-15
    • /
    • 2021
  • Recent genetic advances allow for identification of the genetic etiologies of epilepsy within individual patients earlier and more frequently than ever. Specific targeted treatments have emerged from improvements in understanding of the underlying epileptogenic pathophysiology. These targeted treatment strategies include modifications of ion channels or other cellular receptors and their function, mechanistic target of rapamycin signaling pathways, and substitutive therapies in hereditary metabolic epilepsies. In this review, we explore targeted treatments based on underlying pathophysiologic mechanisms in specific genetic epilepsies.

Inverse association of improved adherence to dietary guidelines with metabolic syndrome: the Seoul Metabolic Syndrome Management program

  • Ham, Dongwoo;Cho, YoungYun;Park, Mi-Suk;Park, Yun-Sug;Kim, Sun-Young;Seol, Hye-Min;Park, Yoo Mi;Woo, Sunok;Joung, Hyojee;Lim, Do-Sun
    • Nutrition Research and Practice
    • /
    • v.14 no.6
    • /
    • pp.621-636
    • /
    • 2020
  • BACKGROUND/OBJECTIVES: The Seoul Metabolic Syndrome Management (SMESY) program is a 1-yr lifestyle modification program targeting metabolic syndrome (MetS) in Seoul residents. This study investigated the associations between adherence to dietary guidelines and MetS among the SMESY program participants. SUBJECTS/METHODS: Data of 54,385 participants aged 20-64 yrs who completed the SMESY program in 2015, had information on adherence to dietary guidelines, and were not medicated for diabetes, hypertension, or dyslipidemia were analyzed. Participants underwent MetS screening and completed a lifestyle questionnaire including adherence to 10 dietary guidelines before and after participation. Participants were classified according to the number of MetS risk factors at baseline (MetS group, ≥ 3; risk group, 1-2; healthy group, none). Adherence to dietary guidelines was determined from the number of "yes" responses regarding the fulfillment of each guideline on ≥ 5 days/week. Multiple logistic regression was used to evaluate associations between newly diagnosed MetS and changes in adherence to dietary guidelines. RESULTS: In the MetS group, MetS prevalence decreased after the SMESY program (men, -41.9%p; women, -48.7%p), and all risk factors were significantly improved (P < 0.0001). All groups exhibited improved adherence to all dietary guidelines after participation (P < 0.0001). In the MetS group with positively changed adherence scores, the MetS prevalence decreased by -44.1%p for men and -49.5%p for women, whereas the prevalence in those with negative changes decreased by -38.1%p for men and -48.6%p for women. In the risk group, those with positively changed adherence scores had significantly decreased odds ratios (ORs) for newly diagnosed MetS compared with those with negative changes (OR, 0.70; 95% confidence interval [CI], 0.61-0.80 for men; OR, 0.88; 95% CI, 0.79-0.99 for women). CONCLUSIONS: The SMESY program may effectively reduce the risk of MetS among adults with risk factors by improving adherence to dietary guidelines.