• 제목/요약/키워드: Translational medical research

검색결과 122건 처리시간 0.04초

Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders

  • Kim, Ki Chan;Gonzales, Edson Luck;Lazaro, Maria T.;Choi, Chang Soon;Bahn, Geon Ho;Yoo, Hee Jeong;Shin, Chan Young
    • Biomolecules & Therapeutics
    • /
    • 제24권3호
    • /
    • pp.207-243
    • /
    • 2016
  • Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

혈관내피세포와 흰쥐 대동맥 미세혈관 발아 모델을 이용한 황금 열수추출물의 세포의 이동, 침투 및 관형성 억제 연구 (Hot Water Extract of Scutellaria baicalensis Inhibits Migration, Invasion and Tube Formation in a Human Umbilical Vein Endothelial Cell Model and a Rat Aortic Ring Sprouting Model)

  • 김억천;배기호;김한성;유영민;겔린스키미첼;김택중
    • 생명과학회지
    • /
    • 제26권1호
    • /
    • pp.91-100
    • /
    • 2016
  • 혈관신생의 억제는 암과 같은 신생혈관형성 질환의 치료를 위해 유용한 접근법이다. 신생혈관형성의 핵심인자인 혈관내피세포성장인자는 신생혈관형성 질환의 치료를 위한 주요한 표적이다. 그러므로, 본 연구에서는 in vitro 분석과 ex vivo 동물 실험을 통해 황금 열수추출물의 신생혈관형성 억제효과를 연구했다. 본 연구결과에서 황금 열수추출물이 혈관내피세포성장인자에 의해 자극된 혈관내피세포에 있어 세포독성 없이 세포의 이동, 침투, 관형성을 농도 의존적으로 억제하였다. 더 나아가 황금 열수추출물은 혈관내피세포성장인자에 의해 유도된 흰쥐 대동맥 주변 미세혈관 발아를 예방하였다. 본 연구결과들은 황금 열수추출물이 신생혈관형성 억제작용이 있고, 이는 혈관내피세포성장인자에 의해 유도된 혈관신생을 억제 하는 잠재적 소재가 될 수 있음을 제안한다.

Diurnal Variation in Hydration of the Cervical Intervertebral Disc Assessed Using T2 Mapping of Magnetic Resonance Imaging

  • Chanyuan Liu;Jingyi Wang;Bowen Hou;Yitong Li;John N. Morelli;Peisen Zhang;Jun Ran;Xiaoming Li
    • Korean Journal of Radiology
    • /
    • 제23권6호
    • /
    • pp.638-648
    • /
    • 2022
  • Objective: The study aimed to investigate the diurnal variation in cervical disc hydration and its relationship with cervical degeneration. Materials and Methods: C3-C7 discs of 86 prospectively enrolled participants (37 males, 49 females; mean age ± standard deviation, 23.5 ± 2.5 years) were assessed using T2 mapping in the morning and evening. All discs were stratified by Miyazaki grade or C2-C7 Cobb angle and T2 values (T2). The degree of diurnal T2 variation (T2-DDV), defined as (morning T2 - evening T2)/morning T2 x 100%, was measured for the entire disc, annulus fibrosus (AF), nucleus pulposus (NP), and endplate zones. Results: T2 of the entire disc decreased significantly after the daytime load (p < 0.001), with a T2-DDV of 13.3% for all discs and 16.0%, 12.2%, and 13.0% for healthy (grade I), mild degenerative (grade II), and advanced degenerative (grade III/IV) discs, respectively. T2 of regional NPs and AFs decreased significantly from morning to evening (p ≤ 0.049) except in the healthy anterior inner AF (p = 0.092). Compared with healthy discs, mild degenerative discs displayed lower T2 and T2-DDV in regional NPs (p < 0.001). Advanced degenerative discs showed higher T2-DDV in the anterior inner AF compared with healthy discs (p = 0.050). Significant diurnal T2 changes in the endplate zones were observed only in healthy discs (p = 0.013). Cervical discs in the low Cobb angle group showed higher T2-DDV in the anterior AFs and anterior NP and lower T2-DDV in the posterior AF than those in the high Cobb angle group (p ≤ 0.041). Conclusion: This study characterized the diurnal variation in hydration of the cervical discs as assessed using T2 mapping and revealed early chemo-mechanical coupling dysfunction in degenerating discs. Cervical sagittal alignment on MRI can affect the diurnal stress patterns of the cervical discs. T2 mapping is sensitive to disc biomechanical dysfunction and offers translational potential from biomechanical research to clinical application.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

  • Li, Xing;Dong, Min;Wen, Jing-Yun;Wei, Li;Ma, Xiao-Kun;Xing, Yan-Fang;Deng, Yun;Chen, Zhan-Hong;Chen, Jie;Ruan, Dan-Yun;Lin, Ze-Xiao;Wang, Tian-Tian;Wu, Dong-Hao;Liu, Xu;Hu, Hai-Tao;Lin, Jia-Yu;Li, Zhuang-Hua;Liu, Yuan-Chao;Xia, Qing;Jia, Chang-Chang;Wu, Xiang-Yuan;Lin, Qu
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권15호
    • /
    • pp.6311-6316
    • /
    • 2015
  • Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

소 설사병 바이러스 구조단백에 대한 단크론항체 성상에 대한 연구 (Monoclonal antibodies against structural proteins of bovine viral diarrhea virus)

  • 권창희;;우희종
    • 대한수의학회지
    • /
    • 제32권1호
    • /
    • pp.83-90
    • /
    • 1992
  • 소 설사병 바이러스 구조단백에 대한 단크론항체를 작성하여 혈청중화시험, 전기영동, 면역침전반응을 이용하여 분석하였던 바 다음의 결과를 얻었다. 중화능력이 있는 항체의 경우 56K내지 54K의 구조단백에 대응하였다. 그외 중화력을 나타내지 않는 항체는 45K와 36K의 바이러스 항원과 대응하였다. 순수정제된 바이러스의 전기영동 분석결과 12종 이상의 바이러스 단백성분이 구조단백질로서 검출되었으며 중화능력을 나타내는 항체를 이용한 면역침전 결과는 이들의 존재를 뒷받침하였다. 중화단백성분의 세포내 전구물질의 검출은 불가능하였으나 방사선동위원소 부착즉시 세포배지에서 바이러스의 존재를 확인할 수 있었다. Staphylococcus aureus $V_8$효소를 이용한 항원의 부분소화 분석결과 45K와 36K의 바이러스 항원은 서로 상관이 있는 것으로서 입증되었다.

  • PDF

Association Analysis of TEC Polymorphisms with Aspirin-Exacerbated Respiratory Disease in a Korean Population

  • Lee, Jin Sol;Bae, Joon Seol;Park, Byung-Lae;Cheong, Hyun Sub;Kim, Jeong-Hyun;Kim, Jason Yongha;Namgoong, Suhg;Kim, Ji-On;Park, Choon-Sik;Shin, Hyoung Doo
    • Genomics & Informatics
    • /
    • 제12권2호
    • /
    • pp.58-63
    • /
    • 2014
  • The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second ($FEV_1$) by aspirin provocation, two variations (rs7664091 and rs12500534) and one haplotype (TEC_BL2_ht4) showed nominal associations with $FEV_1$ decline (p=0.03-0.04). However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.

두경부 편평상피세포암주에서 방사선 내성 관련 유전인자의 확인 (Identifying Genes Related with Radiation Resistance in Oral Squamous Cell Carcinoma Cell Lines)

  • 이세영;설정훈;박행란;조남훈;최윤표;라선영;백승재;황준연;김세헌
    • 대한두경부종양학회지
    • /
    • 제27권2호
    • /
    • pp.190-197
    • /
    • 2011
  • Background and Objective : Radiation resistance(RR) is one of main determinants of treatment outcome in oral squamous cell carcinoma(OSCC), but accurate prediction of RR is difficult. We aim to establish RR OSCC cell lines and identify genes related with RR by a measurement of altered gene expression after inducing RR. Material and Methods : OSCC cell lines, SCC15, SCC25 and QLL1, were treated with 2Gy radiation per session, and parts of them were alive in finally accumulated dosage of 60Gy through 30 times repetition of radiotherapy for inducing RR cell lines. We compared results of cDNA array and proteomics in non-radiated cell lines and RR cell lines to detect changes of gene expression. Western blot was used for the validation of results. Results : cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in 3 RR cell lines comparing their non-radiated counterpart. Among them, 30 cancer related genes were obtained. Proteomics showed 51 commonly altered protein expressions in 3 RR cell lines and 18 cancer related proteins were obtained. Among the detected genes, we found NM23-H1 and PA2G4 were over-expressed in both cDNA array and proteomics. Western blot showed increased expression of NME1 in RR cell lines but not in PA2G4. Conclusion: We concluded that NM23-H1 may be a candidate of RR related gene and over-expression of NM23-H1 could be a biomarker to predict RR in OSCC.

필발(Piper longum Linn.)로부터 전립선암 세포사멸물질 pipernonaline의 분리 및 동정 (Purification and Identification of Apoptosis Modulator Pipernonaline from Piper longum Linn. against Prostate Cancer Cells)

  • 김광연;김윤진;이완;유선녕;조효진;이선이;이한승;손재학;오현철;안순철
    • 생명과학회지
    • /
    • 제19권5호
    • /
    • pp.671-675
    • /
    • 2009
  • Prostate cancer has been a critical health problem due to an increase of prostate cancer-related deaths worldwide. Also, a frequent treatment option for prostate cancer is androgen ablation, but this treatment has a limited scope, especially for hormone-refractory cancer. There is an urgent need for the identification of alternative therapeutic strategies for prostate cancer. Previously, over one hundred species of dried-plant methanol extracts were tested for inhibitory effects on proliferation. One of them, Piper longum Linn. was selected based on its potent anti-proliferation effect. The dried root of P. longum Linn. was extracted with 100% methanol for 2-3 days and its extract was fractionated using chloroform. The chloroform layer was then subjected to column chromatography on silica gel, reverse phase-18 (RP-18) and Sephadex LH-20, in turn. Finally, the pure compound was obtained and identified as pipernonaline by NMR spectroscopic and physico-chemical analysis. In this study, anti-proliferation and cell cycle arrest effects of pipernonaline on human prostate cancer PC-3 cells were investigated using the MTT and PI staining, respectively. Our findings suggest that pipernonaline represents a dose-dependent growth inhibition pattern on PC-3 cells and, moreover, its growth inhibition is associated with sub-G1 and G0/G1 cell cycle accumulation in PC-3 cells. Also, these results provide an anticancer candidate for human prostate cancer.

Dual mechanisms for the regulation of brain-derived neurotrophic factor by valproic acid in neural progenitor cells

  • Ko, Hyun Myung;Jin, Yeonsun;Park, Hyun Ho;Lee, Jong Hyuk;Jung, Seung Hyo;Choi, So Young;Lee, Sung Hoon;Shin, Chan Young
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제22권6호
    • /
    • pp.679-688
    • /
    • 2018
  • Autism spectrum disorders (ASDs) are neurodevelopmental disorders that share behavioral features, the results of numerous studies have suggested that the underlying causes of ASDs are multifactorial. Behavioral and/or neurobiological analyses of ASDs have been performed extensively using a valid model of prenatal exposure to valproic acid (VPA). Abnormal synapse formation resulting from altered neurite outgrowth in neural progenitor cells (NPCs) during embryonic brain development has been observed in both the VPA model and ASD subjects. Although several mechanisms have been suggested, the actual mechanism underlying enhanced neurite outgrowth remains unclear. In this study, we found that VPA enhanced the expression of brain-derived neurotrophic factor (BDNF), particularly mature BDNF (mBDNF), through dual mechanisms. VPA increased the mRNA and protein expression of BDNF by suppressing the nuclear expression of methyl-CpG-binding protein 2 (MeCP2), which is a transcriptional repressor of BDNF. In addition, VPA promoted the expression and activity of the tissue plasminogen activator (tPA), which induces BDNF maturation through proteolytic cleavage. Trichostatin A and sodium butyrate also enhanced tPA activity, but tPA activity was not induced by valpromide, which is a VPA analog that does not induce histone acetylation, indicating that histone acetylation activity was required for tPA regulation. VPA-mediated regulation of BDNF, MeCP2, and tPA was not observed in astrocytes or neurons. Therefore, these results suggested that VPA-induced mBDNF upregulation was associated with the dysregulation of MeCP2 and tPA in developing cortical NPCs.

1차원 배열 탐촉자의 방사빔추적기법을 이용한 정적 3차원 초음파진단영상 구성 (Construction of Static 3D Ultrasonography Image by Radiation Beam Tracking Method from 1D Array Probe)

  • 김용태;도일;안봉영;김광연
    • 비파괴검사학회지
    • /
    • 제35권2호
    • /
    • pp.128-133
    • /
    • 2015
  • 원격진료를 요하는 응급현장에서 사용을 위하여 1차원 배열 탐촉자를 손으로 조작하는 동안 변하는 방사빔의 위치를 추적하여 정적인 3차원 초음파영상을 구성하였다. 탐촉자에 고정된 모션센서의 병진운동 및 회전운동에 대한 정보를 기준직교좌표계로 변환하는 이론적 모델을 제시하였으며, 신호 증폭과 시리얼 통신을 위한 인터페이스 용도의 모듈을 상용의 센서를 사용하여 제작하였다. 실리콘 퍼티로 제작된 시험용 팬텀에 대한 B-모드의 동영상과 센서의 신호를 동기화하여 기록하였다. 동영상으로부터 주기적으로 추출한 B-모드 영상과 각 영상내의 픽셀 각각의 그레이 레벨을 이용하여 3차원 복셀의 그레이 레벨을 재구성하였다. 이 복셀의 데이터를 이용하여 3차원 영상과 임의단면의 B-모드 방식의 2차원 영상을 구성하였으며, 이 영상들은 시험용 팬텀의 형상과 잘 일치하였다.