• Title/Summary/Keyword: Drug targeting

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The Study of Correlation Between the Balance, Cognition and Activity of Daily Living in Stroke Patients (뇌졸중 환자의 균형, 인지, 일상생활 평가의 상관성 연구)

  • Kang, Bo-Ra;Jeong, Eun-Song;Kim, Jae-Hee;Ha, Yoo-Na
    • Journal of Korean Society of Neurocognitive Rehabilitation
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    • v.10 no.2
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    • pp.45-52
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    • 2018
  • The purpose of the present study was to determine correlations between the Berg Balance Scale (BBS), Montreal Cognitive Assessment-Korean (MoCA-K) and Modified Barthel Index (MBI) targeting stroke patients, and it seeks to analyze the influence among each factor to establish the fundamental research in evaluating the functional performance capability of stroke patients. The study was conducted between December 2017 and March 2018 and the target of the study was 34 stroke patients who are hospitalized and treated in Y rehabilitation hospital located in Goyang city. Following in criteria of how participants were selected. First, a person without the onset of 6months or more. Second, a person who can communicate and score over 20 points on MMSE-K. Third, a person without unilateral neglect. Fourth, a person without lower motor neuron lesion and orthopedic disease on the bilateral lower extremity. Fifth, a person without audiovisual problem and history of using drug or surgery that influence athletic function. sixth, patients who agreed on participating in the study. The evaluation was processed by measuring BBS, MoCA-K, and MBI with the occupational therapist and physical therapist. Also, one assistant was participated in measuring balanced ability for the safety reason. It was found that significantly correlates (p<.01) with BBS and MoCA-K (r=.459), BBS and MBI (r=.550), MoCA-K and MBI (r=.565). This study is meaningful that it provided the basis for the active use of BBS, MoCA-K and MBI as a clinical evaluation tool and its usefulness.

A Comparative Study on the Perceptions of Nursing Students and Clinical Instructors on the Importance of Learning Contents of Nursing Management and Practical Experience (간호관리학실습 교과내용에 대한 중요도와 실습 경험에 대한 간호대학생과 임상현장지도자의 인식 비교 연구)

  • Koo, OK-Hee;Hong, Sung-Woo
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.6
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    • pp.90-99
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    • 2021
  • This study was conducted to provide basic data for improving nursing management practice by comparing and analyzing the perceptions of nursing students and clinical instructors about the importance of the learning contents of nursing management and their practical experience. The final 343 copies were analyzed using the Mann-Whitney test and cross-analysis, targeting 4th-grade students and clinical instructors at three universities. Both nursing students and clinical instructors recognized 'communication', 'interpersonal relationship', 'responsibility', 'trust', and 'morality' as important factors in the evaluation items of practice. Among the top 10 most importantly recognized items among nursing-management practice learning content, six items ('infection control', 'nursing record management', 'patient nursing management', 'drug management', 'patient safety', and 'nursing malpractice') were matched in the two groups. Moreover, clinical instructors recognized that interpersonal relationships and relationship ethics were important, while nursing students chose legal responsibility. As a result of the practical experience analysis between the two groups, nursing students had high experience of indirect participation, but the clinical instructors had a high experience of direct instruction. A plan is needed to reduce the difference by establishing an organic partnership relationship between the university and practice institutions and increase the experience of direct practice of nursing students.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

  • Lin, Ching-Ling;Tsai, Ming-Lin;Chen, Yu-hsin;Liu, Wei-Ni;Lin, Chun-Yu;Hsu, Kai-Wen;Huang, Chien-Yu;Chang, Yu-Jia;Wei, Po-Li;Chen, Shu-Huey;Huang, Li-Chi;Lee, Chia-Hwa
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.551-561
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    • 2021
  • Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

Conscious sedation in dentistry: knowledge and practice among dental professionals in Tanzania

  • Sales, Nicco;Sohal, Karpal Singh;Moshy, Jeremiah Robert;Owibingire, Sira Stanslaus;Deoglas, David K;Laizer, Paulo J
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.21 no.6
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    • pp.557-564
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    • 2021
  • Background: Conscious sedation is a useful adjunct in the treatment of patients in dentistry; however, a lack of knowledge among the dental profession regarding sedation is a restricting factor in the practice of dental sedation. Therefore, this study was conducted to assess the knowledge and practice of sedation in dentistry among dental professionals in Tanzania. Methods: This was a cross-sectional study conducted for five months targeting all practicing dental professionals in Tanzania. A modified questionnaire contained 14 questions regarding knowledge about sedative agents and a section on the practice of sedation. The data obtained from this study were coded and entered into a computer program and analyzed using SPSS software version 23.0. The data are presented as frequencies and percentages in tables and charts. Statistical significance was set at P < 0.05. Results: The age range of participants was between 24 and 63 years (mean 36.6 ± 7.7 years). There were 107 men (78.1%), and the male-to-female ratio was 3.6:1. The majority (76.6%) of participants only had an undergraduate dental degree. Thirty-one percent of participants only worked in publicly owned health facilities. Slightly more than half (59.9%) of participants had satisfactory knowledge regarding sedation in dentistry. There was no statistically significant association between the level of sedation-related knowledge and the demographic characteristics of the participants. Only 21.9% reported using sedation in their practice, and the most commonly used sedative drug was diazepam. The reasons for not using dental sedation in clinical practice included a perceived lack of knowledge on sedation, lack of equipment, and cost. Conclusion: Most dental professionals in Tanzania have basic knowledge of sedation in dentistry, although knowledge regarding sedative agents is generally low. The practice of sedation in dentistry in Tanzania is very low compared to that in middle- and high-income countries. Inadequate knowledge, lack of equipment, and the cost of practicing sedation are the main reasons for not practicing sedation.

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

  • Younghoon Jang
    • Journal of Life Science
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    • v.33 no.3
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    • pp.287-294
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    • 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.

RUNX1-Survivin Axis Is a Novel Therapeutic Target for Malignant Rhabdoid Tumors

  • Masamitsu, Mikami;Tatsuya, Masuda;Takuya, Kanatani;Mina, Noura;Katsutsugu, Umeda;Hidefumi, Hiramatsu;Hirohito, Kubota;Tomoo, Daifu;Atsushi, Iwai;Etsuko Yamamoto, Hattori;Kana, Furuichi;Saho, Takasaki;Sunao, Tanaka;Yasuzumi, Matsui;Hidemasa, Matsuo;Masahiro, Hirata;Tatsuki R., Kataoka;Tatsutoshi, Nakahata;Yasumichi, Kuwahara;Tomoko, Iehara;Hajime, Hosoi;Yoichi, Imai;Junko, Takita;Hiroshi, Sugiyama;Souichi, Adachi;Yasuhiko, Kamikubo
    • Molecules and Cells
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    • v.45 no.12
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    • pp.886-895
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    • 2022
  • Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin

  • Seung-On Lee;Sang Hoon Joo;Jin-Young Lee;Ah-Won Kwak;Ki-Taek Kim;Seung-Sik Cho;Goo Yoon;Yung Hyun Choi;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.104-114
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    • 2024
  • Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Enhanced Drug Carriage Efficiency of Curcumin-Loaded PLGA Nanoparticles in Combating Diabetic Nephropathy via Mitigation of Renal Apoptosis

  • Asmita Samadder;Banani Bhattacharjee;Sudatta Dey;Arnob Chakrovorty;Rishita Dey;Priyanka Sow;Debojyoti Tarafdar;Maharaj Biswas;Sisir Nandi
    • Journal of Pharmacopuncture
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    • v.27 no.1
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    • pp.1-13
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    • 2024
  • Background: Diabetic nephropathy (DN) is one of the major complications of chronic hyperglycaemia affecting normal kidney functioning. The ayurvedic medicine curcumin (CUR) is pharmaceutically accepted for its vast biological effects. Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.

Smad6 Gene and Suppression of Radiation-Induced Apoptosis by Genistein in K562 Cells (K562 세포주에서 Genistein에 의해 억제되는 Radiation-induced Apoptosis의 조절 유전자)

  • Jeong, Soo-Jin;Jin, Young-Hee;Yoo, Yeo-Jin;Do, Chang-Ho;Jeong, Min-Ho;Huh, Gi-Yeong;Bae, Hye-Ran;Yang, Kwang-Mo;Moon, Chang-Woo;Oh, Sin-Geun;Hur, Won-Joo;Lee, Hyung-Sik
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.245-251
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    • 2001
  • Prupose : The genes involved on the suppression or radiation-induced apoptosis by genistein in K562 leukemia cell line was investigated. Materials and methods : K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For X-ray irradiation and drug treatment, cultures were prepared at $2\times10^5\;cells/mL$. The cells were irradiated with 10 Gy (Clinac 1800C, Varian, USA), Stock solutions of herbimycin A (HMA, Calbiochem, UK) and genistein (Calbiochem, UK) were prepared in dimethylsulfoxide (DMSO, Sigma, UK). After incubation at $37^{\circ}C$ for 24 h, PCR-select cDNA subtractive hybridization, dot hybridization, DNA sequencing and Northern hybridization were examined. Results : Smad6 gene was identified from the differentially expressed genes in K562 cells incubated with genistein which had been selected by PCR-select cDNA subtractive hybridization. The mRNA expression of Smad6 in K562 cells incubated with genistein was also higher than control group by Northern hybridization analysis. Conclusion : We have shown that Smad6 involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line. It is plausible that the relationship between Smad6 and the suppression of radiation-induced apoptosis is essential for treatment development based on molecular targeting designed to modify radiation-induced apoptosis.

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Evaluation of Commercial Complementary DNA Synthesis Kits for Detecting Human Papillomavirus (인유두종바이러스 검출을 위한 상용화된 cDNA 합성 키트의 평가)

  • Yu, Kwangmin;Park, Sunyoung;Chang, Yunhee;Hwang, Dasom;Kim, Geehyuk;Kim, Jungho;Kim, Sunghyun;Kim, Eun-Joong;Lee, Dongsup
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.3
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    • pp.309-315
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    • 2019
  • Cervical cancer is the fourth most common malignant neoplasm in women worldwide. Most cases of cervical cancer are caused by an infection by the human papillomavirus. Molecular diagnostic methods have emerged to detect the HPV for sensitivity, specificity, and objectivity. In particular, real-time PCR has been introduced to acquire a more sensitive target DNA or RNA. RNA extraction and complementary DNA synthesis are proceeded before performing real-time PCR targeting RNA. To identify an adequate and sensitive cDNA synthesis kit, this study evaluated the two commonly used kits for cDNA synthesis. The results show that the $R^2$ and efficiency (%) of the two cDNA synthesis kits were similar in the cervical cancer cell lines. On the other hand, the Takara kit compared to Invitrogen kit showed P<0.001 in the $10^2$ and $10^3$ SiHa cell count. The Takara kit compared to the Invitrogen kit showed P<0.001 in the $10^1$ and $10^2$ HeLa cell count. Furthermore, 8, 4, 2, 1, and 0.5 ml of forty exfoliated cell samples were used to compare the cDNA synthesis kits. The Takara kit compared to the Invitrogen kit showed P<0.01 in 8, 4, and 1 ml and P<0.05 in 0.5 mL. The study was performed to identify the most appropriate cDNA synthesis kit and suggests that a cDNA synthesis kit could affect the real-time PCR results.