• Title/Summary/Keyword: translational research

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Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

  • Won Kyu Kim;Wooseon Choi;Barsha Deshar;Shinwon Kang;Jiyoon Kim
    • Molecules and Cells
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    • v.46 no.4
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    • pp.191-199
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    • 2023
  • The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to the insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

Indications for Dental Floss Clip Traction During Gastric Endoscopic Submucosal Dissection by Less-Experienced Endoscopists

  • Hirosato Tamari;Shiro Oka;Takahiro Kotachi;Hajime Teshima;Junichi Mizuno;Motomitsu Fukuhara;Hidenori Tanaka;Akiyoshi Tsuboi;Ken Yamashita;Ryo Yuge;Yuji Urabe;Yasuhiko Kitadai;Koji Arihiro;Shinji Tanaka
    • Journal of Gastric Cancer
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    • v.23 no.4
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    • pp.512-522
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    • 2023
  • Purpose: Dental floss clip (DFC) traction-assisted endoscopic submucosal dissection (ESD) is widely performed owing to its simplicity. This study aimed to clarify the appropriate indications for the DFC traction method in early gastric cancer when ESD is performed by less-experienced endoscopists. Methods and Methods: We retrospectively analyzed 1,014 consecutive patients who had undergone gastric ESD performed by less-experienced endoscopists between January 2015 and December 2020. Gastric ESD was performed without DFC in all cases before December 2017 [DFC (-) group, 376 cases], and ESD was performed with DFC in all cases after January 2018 [DFC (+) group, 436 cases]. The procedure time and rates of en bloc resection, complete resection, and adverse events of the groups were compared. Results: The procedure time did not differ significantly between the 2 groups. However, when comparing lesions >20 mm, the procedure time in the DFC (+) group was significantly shorter than that in the DFC (-) group (95±46 vs. 75±31, P<0.01). The procedure time for lesions located in the greater curvature of the upper or middle stomach and lesions >20 mm located in the lesser curvature side of the stomach in the DFC (+) group was significantly shorter than that in the DFC (-) group. Conclusions: The indications for DFC during gastric ESD by less-experienced endoscopists include lesions located in the greater curvature of the upper or middle stomach, and lesions >20 mm located in the lesser curvature of the stomach.

Comparison of 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma using endoscopic ultrasound fine-needle aspiration

  • Mitsuru Okuno;Keisuke Iwata;Tsuyoshi Mukai;Yusuke Kito;Takuji Tanaka;Naoki Watanabe;Senji Kasahara;Yuhei Iwasa;Akihiko Sugiyama;Youichi Nishigaki;Yuhei Shibata;Junichi Kitagawa;Takuji Iwashita;Eiichi Tomita;Masahito Shimizu
    • Clinical Endoscopy
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    • v.57 no.3
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    • pp.364-374
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    • 2024
  • Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML). Methods: Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles. Results: Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1-6] vs. 4 [1-6], p=0.023). There were no significant differences in cytological/ histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding as adverse events (AEs) were observed in three patients in the Franseen group. Conclusions: Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy.

Maximal strength and endurance scores of the tongue, lip, and cheek in healthy, normal Koreans

  • Jeong, Dong-Min;Shin, Yoo-Jin;Lee, Na-Ra;Lim, Ho-Kyung;Choung, Han-Wool;Pang, Kang-Mi;Kim, Bong-Ju;Kim, Soung-Min;Lee, Jong-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.43 no.4
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    • pp.221-228
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    • 2017
  • Objectives: The purpose of this study was to establish normative data for healthy Korean adults by measuring the maximal strength and endurance scores of the tongue, lip, and cheek, and to examine correlations between these measurements. Materials and Methods: This study included 120 subjects that were divided into three groups according to age: young (20-39 years), middle-aged (40-59 years), and older (over 60 years); and by gender. Measurements were taken using the Iowa Oral Performance Instrument (IOPI). Results: The mean maximal tongue strengths were as follows: young men ($46.7{\pm}10.2kPa$) and women ($32.1{\pm}7.9kPa$), middle-aged men ($40.9{\pm}9.3kPa$) and women ($36.9{\pm}8.6kPa$), and older men ($35.2{\pm}9.0kPa$) and women ($34.5{\pm}6.9kPa$). The mean tongue endurance scores were: young men ($28.8{\pm}12.6$ seconds) and women ($20.8{\pm}13.5$ seconds), middle-aged men ($17.0{\pm}8.5$ seconds) and women ($15.3{\pm}5.2$ seconds), and older men ($15.8{\pm}6.7$ seconds) and women ($17.9{\pm}8.1$ seconds). The mean maximal lip strengths were: young men ($11.6{\pm}3.0kPa$) and women ($11.4{\pm}3.8kPa$), middle-aged men ($11.4{\pm}4.2kPa$) and women ($11.1{\pm}5.1kPa$), and older men ($14.5{\pm}3.9kPa$) and women ($11.7{\pm}2.6kPa$). The mean lip endurance scores were: young men ($41.1{\pm}23.9$ seconds) and women ($22.4{\pm}21.7$ seconds), middle-aged men ($24.3{\pm}10.3$ seconds) and women ($30.5{\pm}13.4$ seconds), and older men ($24.9{\pm}11.0$ seconds) and women ($12.8{\pm}7.6$ seconds). The mean maximal cheek strengths were: young men ($24.5{\pm}4.6kPa$) and women ($20.5{\pm}4.3kPa$), middle-aged men ($25.2{\pm}6.4kPa$) and women ($21.2{\pm}5.5kPa$), and older men ($22.4{\pm}5.3kPa$) and women ($18.0{\pm}4.8kPa$). The mean cheek endurance scores were: young men ($47.8{\pm}24.4$ seconds) and women ($43.9{\pm}25.0$ seconds), middle-aged men ($27.3{\pm}11.3$ seconds) and women ($20.0{\pm}14.6$ seconds), and older men ($21.7{\pm}14.5$ seconds) and women ($17.2{\pm}11.4$ seconds). Conclusion: The data collected in this study will provide an important database of standardized measurements for maximal strength and endurance scores of the tongue, lip and cheek in healthy, normal Koreans.

Molecular Cloning of Two Genes Encoding Cinnamate 4-Hydroxylase (C4H) from Oilseed Rape (Brassica napus)

  • Chen, An-He;Chai, You-Rong;Li, Jia-Na;Chen, Li
    • BMB Reports
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    • v.40 no.2
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    • pp.247-260
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    • 2007
  • Cinnamate 4-hydroxylase (C4H) is a key enzyme of phenylpropanoid pathway, which synthesizes numerous secondary metabolites to participate in development and adaption. Two C4H isoforms, the 2192-bp BnC4H-1 and 2108-bp BnC4H-2, were cloned from oilseed rape (Brassica napus). They both have two introns and a 1518-bp open reading frame encoding a 505-amino-acid polypeptide. BnC4H-1 is 57.73 kDa with an isoelectric point of 9.11, while 57.75 kDa and 9.13 for BnC4H-2. They share only 80.6% identities on nucleotide level but 96.6% identities and 98.4% positives on protein level. Showing highest homologies to Arabidopsis thaliana C4H, they possess a conserved p450 domain and all P450-featured motifs, and are identical to typical C4Hs at substrate-recognition sites and active site residues. They are most probably associated with endoplasmic reticulum by one or both of the N- and C-terminal transmembrane helices. Phosphorylation may be a necessary post-translational modification. Their secondary structures are dominated by alpha helices and random coils. Most helices locate in the central region, while extended strands mainly distribute before and after this region. Southern blot indicated about 9 or more C4H paralogs in B. napus. In hypocotyl, cotyledon, stem, flower, bud, young- and middle-stage seed, they are co-dominantly expressed. In root and old seed, BnC4H-2 is dominant over BnC4H-1, with a reverse trend in leaf and pericarp. Paralogous C4H numbers in Brassicaceae genomes and possible roles of conserved motifs in 5' UTR and the 2nd intron are discussed.

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

  • Lee, Sei-Young;Seol, Jeong-Hun;Park, Haeng-Ran;Cho, Nam-Hoon;Choi, Yoon-Pyo;Rha, Sun-Young;Baek, Seung-Jae;Hwang, Jun-Yeon;Kim, Se-Heon
    • Korean Journal of Head & Neck Oncology
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    • v.27 no.2
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    • pp.190-197
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    • 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.

Autocrine Regulation of Gonadotropin-releasing Hormone (GnRH) Operates at Multiple Control levels of GnRH Gene Expression in GT1-1 Neuronal Cells

  • Jin Han;Sehyung Cho;Woong Sun;Kyungjin Kim
    • Animal cells and systems
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    • v.2 no.4
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    • pp.483-488
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    • 1998
  • We previously found that a potent gonadotropin-releasing hormone (GnRH) agonist, buserelin, decreases GnRH promoter activity together with GnRH mRNA level, providing evidence for an autoregulatory mechanism operating at the level of GnRH gene transcription in immortalized GT1-1 neuronal cells. To examine whether agonist-induced decrease in GnRH mRNA level requires the continuous presence of buserelin, we performed a pulse-chase experiment of buserelin treatment. Short-term exposure (15 min) of GT1-1 neuronal cells to buserelin ($10{\mu}M$) was able to decrease GnRH mRNA levels when determined 24 h later. When GT1-1 cells were treated with buserelin ( $10{\mu}M$) for 30 min and then incubated for 1, 3, 6, 12, 24, and 48 h after buserelin removal, a significant decrease in GnRH mRNA levels was observed after the 12 h incubation period. These data indicate that inhibitory signaling upon buserelin treatment may occur rapidly, but requires a long time (at least 12 h) to significantly decrease the GnRH mRNA level. To examine the possible involvement of de novo synthesis and/or mRNA stability in buserelin-induced decrease in GnRH gene expression, actinomycin D ($5{\mu}m/ml$), a potent RNA synthesis blocker, was co-treated with buserelin. Actinomycin D alone failed to alter basal GnRH mRNA Revel, but blocked the buserelin-induced decrease in GnRH mRNA level at 12 h of post-treatment. These data suggest that buserelin may exert its inhibitory action by altering the stability of GnRH mRNA. Moreover, a polvsomal RNA separation by sucrose gradient centrifugation demonstrated that buserelin decreased the translational efficiency of the transcribed GnRH mRNA. Taken together, these results clearly indicate that GnRH agonist buserelin acts as an inhibitory signal at multiple levels such as transcription mRNA stability, and translation.

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Association between Laryngeal Squamous Cell Carcinoma and Polymorphisms in Tumor Necrosis Factor Related Apoptosis Induce Ligand (TRAIL), TRAIL Receptor and sTRAIL Levels

  • Verim, Aysegul;Turan, Saime;Farooqi, Ammad Ahmad;Kahraman, Ozlem Timirci;Tepe-Karaca, Cigdem;Yildiz, Yemliha;Naiboglu, Baris;Ozkan, Nazli Ezgi;Ergen, Arzu;Isitmangil, Gulbu Aydinoglu;Yaylim, Ilhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10697-10703
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    • 2015
  • The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.

Risk-Scoring System for Prediction of Non-Curative Endoscopic Submucosal Dissection Requiring Additional Gastrectomy in Patients with Early Gastric Cancer

  • Kim, Tae-Se;Min, Byung-Hoon;Kim, Kyoung-Mee;Yoo, Heejin;Kim, Kyunga;Min, Yang Won;Lee, Hyuk;Rhee, Poong-Lyul;Kim, Jae J.;Lee, Jun Haeng
    • Journal of Gastric Cancer
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    • v.21 no.4
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    • pp.368-378
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    • 2021
  • Purpose: When patients with early gastric cancer (EGC) undergo non-curative endoscopic submucosal dissection requiring gastrectomy (NC-ESD-RG), additional medical resources and expenses are required for surgery. To reduce this burden, predictive model for NC-ESD-RG is required. Materials and Methods: Data from 2,997 patients undergoing ESD for 3,127 forceps biopsy-proven differentiated-type EGCs (2,345 and 782 in training and validation sets, respectively) were reviewed. Using the training set, the logistic stepwise regression analysis determined the independent predictors of NC-ESD-RG (NC-ESD other than cases with lateral resection margin involvement or piecemeal resection as the only non-curative factor). Using these predictors, a risk-scoring system for predicting NC-ESD-RG was developed. Performance of the predictive model was examined internally with the validation set. Results: Rate of NC-ESD-RG was 17.3%. Independent pre-ESD predictors for NC-ESD-RG included moderately differentiated or papillary EGC, large tumor size, proximal tumor location, lesion at greater curvature, elevated or depressed morphology, and presence of ulcers. A risk-score was assigned to each predictor of NC-ESD-RG. The area under the receiver operating characteristic curve for predicting NC-ESD-RG was 0.672 in both training and validation sets. A risk-score of 5 points was the optimal cut-off value for predicting NC-ESD-RG, and the overall accuracy was 72.7%. As the total risk score increased, the predicted risk for NC-ESD-RG increased from 3.8% to 72.6%. Conclusions: We developed and validated a risk-scoring system for predicting NC-ESD-RG based on pre-ESD variables. Our risk-scoring system can facilitate informed consent and decision-making for preoperative treatment selection between ESD and surgery in patients with EGC.

Impact of Indoor Plants on Indoor Air Quality and Occupational Health in Newly Built Public Building Offices - Focusing on Allergic Conjunctivitis and Stress-related Symptom Questionnaires - (신축건물 사무실내 식물 적용의 실내 공기질 및 재실자 건강영향 평가 - 알레르기 비결막염 및 스트레스 관련 증상설문을 중심으로 -)

  • Lee, Yong Won;Lim, Young Wook;Kim, Kwang-Jin;Kim, Ho-Hyun
    • Journal of Environmental Health Sciences
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    • v.43 no.4
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    • pp.334-348
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    • 2017
  • Objectives: We investigated the impacts of indoor plants on indoor air quality and occupational health, focusing on allergic rhinconjunctivitis and stress among employees in new office buildings. Methods: A total of 34 employees working at new public office buildings were enrolled as subjects (n=17, with indoor plants) and as a control (n=17) group. Before and after introducing indoor plants for three months, indoor air quality measurements including VOCs and aldehydes and questionnaires on sick building syndrome, AR symptoms (ARIA based), stress (DASS 42, KOSS, and SACL), and indoor characteristics were performed and statistically analysed. Results: Among the 34 enrolled subjects, 19 were included in the probable AR subject group (subjects with indoor plants, n=8, control n=11) and completed all questionnaires. Statistical analyses were done for total, AR subject groups, and controls. As a result, it was confirmed that major indoor air pollutants decreased after the introduction of indoor plants (p<0.5). Among major symptoms of allergic rhinoconjunctivitis, watery rhinorrhea, nasal stuffiness, and nasal itching indexes decreased (p<0.5, respectively). A decrease was noted in some areas of work-related stress indexes (mainly KOSS) among the subject group (total and AR) and a decrease of indoor environmental attractiveness among the control group (total and AR) (p<0.5, for all). Conclusions: Indoor plants may help reduce indoor air pollutants and decrease AR symptoms and work-related stress of employees in newly built office buildings. Various further follow-up studies on the mechanism of environmental, physical, and emotional influences and utilization of indoor plants in association with allergic diseases will be needed.