• Title/Summary/Keyword: risk expression

Search Result 623, Processing Time 0.023 seconds

Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains demonstrates phenotypic variability by Rg3 treatment

  • Bao Ngoc Nguyen;Soyeon Hong;Sowoon Choi;Choong-Gu Lee;GyHye Yoo;Myungsuk Kim
    • Journal of Ginseng Research
    • /
    • v.48 no.3
    • /
    • pp.310-322
    • /
    • 2024
  • Background: Osteosarcopenia is a common condition characterized by the loss of both bone and muscle mass, which can lead to an increased risk of fractures and disability in older adults. The study aimed to elucidate the response of various mouse strains to treatment with Rg3, one of the leading ginsenosides, on musculoskeletal traits and immune function, and their correlation. Methods: Six Collaborative Cross (CC) founder strains induced muscle atrophy and bone loss with dexamethasone (15 mg/kg) treatment for 1 month, and half of the mice for each strain were orally administered Rg3 (20 mg/kg). Different responses were observed depending on genetic background and Rg3 treatment. Results: Rg3 significantly increased grip strength, running performance, and expression of muscle and bone health-related genes in a two-way analysis of variance considering the genetic backgrounds and Rg3 treatment. Significant improvements in grip strength, running performance, bone area, and muscle mass, and the increased gene expression were observed in specific strains of PWK/PhJ. For traits related to muscle, bone, and immune functions, significant correlations between traits were confirmed following Rg3 administration compared with control mice. The phenotyping analysis was compiled into a public web resource called Rg3-OsteoSarco. Conclusion: This highlights the complex interplay between genetic determinants, pathogenesis of muscle atrophy and bone loss, and phytochemical bioactivity and the need to move away from single inbred mouse models to improve their translatability to genetically diverse humans. Rg3-OsteoSarco highlights the use of CC founder strains as a valuable tool in the field of personalized nutrition.

Role of TGF-β1/SMADs signalling pathway in resveratrol-induced reduction of extracellular matrix deposition by dexamethasone-treated human trabecular meshwork cells

  • Amy Suzana Abu Bakar;Norhafiza Razali;Renu Agarwal;Igor Iezhitsa;Maxim A. Perfilev;Pavel M. Vassiliev
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.28 no.4
    • /
    • pp.345-359
    • /
    • 2024
  • Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM) increases aqueous humour outflow resistance leading to elevation of intraocular pressure (IOP) in primary open-angle glaucoma, which remains the only modifiable risk factor. Resveratrol has been shown to counteract the steroid-induced increase in IOP and increase the TM expression of ECM proteolytic enzymes; however, its effects on the deposition of ECM components by TM and its associated pathways, such as TGF-β-SMAD signalling remain uncertain. This study, therefore, explored the effects of trans-resveratrol on the expression of ECM components, SMAD signalling molecules, plasminogen activator inhibitor-1 and tissue plasminogen activator in dexamethasone-treated human TM cells (HTMCs). We also studied the nature of molecular interaction of trans-resveratrol with SMAD4 domains using ensemble docking. Treatment of HTMCs with 12.5 µM trans-resveratrol downregulated the dexamethasone-induced increase in collagen, fibronectin and α-smooth muscle actin at gene and protein levels through downregulation of TGF-β1, SMAD4, and upregulation of SMAD7. Downregulation of TGF-β1 signalling by trans-resveratrol could be attributed to its effect on the transcriptional activity due to high affinity for the MH2 domain of SMAD4. These effects may contribute to resveratrol's IOP-lowering properties by reducing ECM deposition and enhancing aqueous humour outflow in the TM.

Mechanism of Formononetin-induced Stimulation of Adipocyte Fatty Acid Oxidation and Preadipocyte Differentiation

  • Seok-Yeong Yu;Youngmin Choi;Young-In Kwon;Ok-Hwan Lee;Young-Cheul Kim
    • Journal of Food and Nutrition Research
    • /
    • v.9 no.3
    • /
    • pp.163-169
    • /
    • 2021
  • Decreased adipocyte fatty acid oxidation (FAO) and impaired preadipocyte differentiation characterize hypertrophic expansion of adipose tissue (AT) from obese and insulin resistant humans and are recognized as potential mechanisms for obesity-mediated dyslipidemia. Supplementation of formononetin (FMN), one of the principal isoflavones extracted from red clover or Huangqi (Astragalus roots), has been shown to have beneficial effects on obesity-related hyperlipidemia, a well-established cardiovascular risk factor. However, a target tissue and underlying mechanism(s) through which FMN acts have been under-investigated. Thus, we investigated whether FMN promotes adipocyte FAO and preadipocyte differentiation using 3T3-L1 preadipocytes to provide potential mechanisms of FMN action. We further extended this to the culture of 10T1/2 mesenchymal stem cells (MSCs) as well as mouse AT explants to reflect in vivo effects of FMN. In fully differentiated 3T3-L1 adipocytes, FMN-treatment significantly increased the expression levels of FAO-related proteins such as pAMPK, pACC, and CPT1, all of which were consistently upregulated in AT explant cultures treated with 10 μM FMN. In addition, FMN significantly enhanced the degree of differentiation of both 3T3-L1 preadipocytes and 10T1/2 MSCs into adipocytes as evidenced by Oil Red O staining of cellular lipids. This observation correlated with increased expression levels of key adipogenic transcription factors (PPARγ and C/EBPα) and their down-stream target proteins (FABP4, Glut4 and adiponectin). Moreover, FMN failed to exert its stimulatory effects on preadipocyte differentiation in both cell types in the presence of a PPARγ antagonist, suggesting a PPARγ-dependent effect of FMN. Collectively, these data provide possible mechanisms of action of FMN on lipid metabolism and further support the favorable in vivo effects of FMN in diet and obesity-induced dyslipidemia.

Evaluation of Estrogenic Activity of Extract from the Herbal Mixture Cynanchum wilfordii Hemsley, Phlomis umbrosa Turczaninow, and Angelica gigas Nakai

  • Kim, Se Jong;Jin, Sun Woo;Lee, Gi-Ho;Kim, Yong An;Jeong, Hye Gwang
    • Toxicological Research
    • /
    • v.33 no.1
    • /
    • pp.71-77
    • /
    • 2017
  • Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

Epigenetic Changes in Asthma: Role of DNA CpG Methylation

  • Bae, Da-Jeong;Jun, Ji Ae;Chang, Hun Soo;Park, Jong Sook;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
    • /
    • v.83 no.1
    • /
    • pp.1-13
    • /
    • 2020
  • For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the 'missing' heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

Breast Cancer Metastasis Associations with Clinicopathological Characteristics in Mexican Women Younger than 40 Years of Age

  • Rosales, Azucena Moreno;Molina, Miguel Corres;Moo, Jacqueline Gongora;Morelos, Pablo Romero;Bandala, Cindy
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.17 no.11
    • /
    • pp.5019-5023
    • /
    • 2016
  • Background: In Mexico, breast cancer (BCa) is in first place regarding cancer mortality and has been established as a priority health issue. The incidence of metastasis from BCa is very high and presents as the principal mortality factor among women younger than 40 years of age. OBJECTIVE. To determine any associations between clinicopathological characteristics and metastasis in Mexican women under 40 years of age. Methods: During the 2010-2015 period, a total of 180 female BCa cases seen at the Navy General High Specialty Hospital, SEMAR, in Mexico City; we collected information on 20 patients with BCa younger than 40 years of age. Statistical analyses were conducted using the Kolmogorov-Smirnov, Students t, Fisher, Chi square, and Mantel-Haenszel tests. Results: The prevalence of women with BCa younger than the age of 40 years during the 2010-2015 period was 13.3%. We found a high frequency of obesity in of these cases (>75%); 100% of obese patients with a history of smoking presented with metastasis (p <0.05). In addition, the hormone phenotype was important; HER2-positive cases were 12 times more likely tto exhibit metastasis (p <0.05), while expression of estrogen and progesterone receptors appeared to be protective. Diabetes mellitus in combination with smoking was also a risk factor for development of metastasis (p <0.05). Conclusion: In this study, we obtained essential data regarding risk of metastasis in young breast cancer cases which could be useful for predicting disease evolution and treatment response.

Benefits of Metformin Use for Cholangiocarcinoma

  • Kaewpitoon, Soraya J;Loyd, Ryan A;Rujirakul, Ratana;Panpimanmas, Sukij;Matrakool, Likit;Tongtawee, Taweesak;Kootanavanichpong, Nusorn;Kompor, Ponthip;Chavengkun, Wasugree;Kujapun, Jirawoot;Norkaew, Jun;Ponphimai, Sukanya;Padchasuwan, Natnapa;Pholsripradit, Poowadol;Eksanti, Thawatchai;Phatisena, Tanida;Kaewpitoon, Natthawut
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.18
    • /
    • pp.8079-8083
    • /
    • 2016
  • Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention.

A Study of the Classification of Nursing Diagnoses (간호진단 분석 일 연구)

  • Shon Young-Hee
    • Journal of Korean Academy of Fundamentals of Nursing
    • /
    • v.4 no.1
    • /
    • pp.119-131
    • /
    • 1997
  • This study was conducted to analyze the nursing diagnoses applied for case studies of nursing students through their clinical practices, and to provide the educational basis of nursing diagnoses with its results. The data were collected for two years(1995 and 1996) from 70 case studies reported by the 2nd and 3rd year nursing junior college students. The students made 259 nursing diagnoses among which 230 diagnoses qualified NANDA classification and were taken for analysis. The results of the analysis were as follows : 1. The number of diagnoses indicating response patterns was 35(35.7%), whereas 98 diagnoses in NANDA table. Among the 35 diagnoses, the pattern of exchange was most frequent, then feeling, moving, knowing in rank. 2. The diagnoses were analyzed in the categories of response patterns. For Instance, 'Altered in Nutrition' was most frequent in exhange, then Risk for Infection', 'Ineffective Airway Clearance', in rank. 3. Among 230 diagnoses, 'Knowle Deficit' was most frequently mentioned, then 'Activity Intolerance' 'Anxiety', 'Pain', 'Altered in Nutrition', 'Risk for Infection', 'Ineffective airway clearance', in rank. 4. The types of word expression of each diagnoses were various. 'Activity Intolerance' was expressed in 6 types. 5. The relating factors applied to each diagnosis were analyzed. For Instance, the relating factor of 'Knowledge Deficit' were illness, and therapeutic process, lack of motivation, occurrance of complication, short experience, operation, and so on. From the above study, the researcher would like to recommend as follows : 1) The current diagnoses need to be verified its content validity, when they are applied to our culture. 2) The most effective educational method for applying nursing diagnoses should be explored. 3) Further study could be focused on not only 'relating factors' but also 'sign and symptoms'.

  • PDF

Molecular biological characteristics and analysis using the specific markers of leaf folder-resistant GM rice (혹명나방저항성 GM 벼의 분자생물학적 특성 및 특이 마커를 이용한 검정)

  • Shin, Kong-Sik;Lee, Si-Myoung;Lim, Sun-Hyung;Woo, Hee-Jong;Cho, Hyun-Suk;Lee, Kyeong-Ryeol;Lee, Myung-Chul;Kweon, Soon-Jong;Suh, Seok-Cheol
    • Journal of Plant Biotechnology
    • /
    • v.36 no.2
    • /
    • pp.115-123
    • /
    • 2009
  • In recent years, several genetically modified (GM) crops have been developed worldwide through the recombinant DNA technology and commercialized by various agricultural biotechnological companies. Commercialization of GM crops will be required the assesment of risks associated with the release of GM crops. In advance of the commercial release of GM crops, developer should submit the several information on GM crops for approval. In this study, we carried out to provide the molecular data for the risk assessment of GM rice containing insect-resistant gene, modified Cry1Ac (CryIAc1). Through the molecular analysis with CryIAc1 induced GM rice, we confirmed the steady integration and expression of transgene, the transgene copy number, the adjacent region sequences of inserted gene into rice genome, and the transgene stability in progenies. For the qualitative PCR detection methods, specific primer pairs were designed on the basis of integration sequences, and construct- and event-specific detection markers were developed for leaf folder-resistant rice, Cr7-1 line. From these results, we demonstrated that the molecular data and the PCR detection methods of leaf folderresistant GM rice could be acceptable to conduct the biosafety and environment risk assessment.

Prediction Value of XRCC 1 Gene Polymorphism on the Survival of Ovarian Cancer Treated by Adjuvant Chemotherapy

  • Miao, Jin;Zhang, Xian;Tang, Qiong-Lan;Wang, Xiao-Yu;Kai, Li
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.10
    • /
    • pp.5007-5010
    • /
    • 2012
  • Objective: We conducted a prospective study to test the association between three amino acid substitution polymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1 (Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. Methods: 195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in our study. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conducted by TaqMan Gene Expression assays. Results: The XRCC1 194 Trp/Trp genotype conferred a significant risk of death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, those carrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). Conclusion: This study is the first to provide evidence that XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovarian cancer cases undergoing adjuvant chemotherapy.