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Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials

  • Hyeonjin Kim;Soohyun Jeong;Sung Wook Kim;Hyung-Jin Kim;Dae Yong Kim;Tae Han Yook;Gabsik Yang
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.59-69
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    • 2024
  • This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

A Statistical Analysis of Outpatients in Ophthalmology and Otolaryngology of Korean Medicine at Kyung Hee University Korean Medicine Hospital in 2018-2022 (2018-2022년 경희대학교 한방병원 한방 안이비인후과 외래환자에 대한 통계분석)

  • Byunghyun Kim;YeEun Hong;EunKyung Lee;Heejae Lee;Kyuseok Kim;HaeJeong Nam;YoonBum Kim
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.37 no.2
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    • pp.1-13
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    • 2024
  • Objectives : The purpose of this study is to figure out the changes in sex, age, disease distribution of outpatients in ophthalmology and otolaryngology of Korean medicine. Methods : We analyzed the medical records of 2,834 outpatients who visited department of ophthalmology and otolaryngology of Korean medicine at Kyung Hee university Korean medicine hospital between 2018 and 2022. And we compared the results with those of studies from 2000, 2007, and 2017, considering sex, age, and diseases. Results : 1. The total number of patients in ophthalmology and otolaryngology increased compared to 2012-2016, with a higher proportion of patients aged 50 and above in all departments. 2. The number of patients in ophthalmology has been continuously decreasing since 1996-1998. 3. The number of patients in otology has increased significantly compared to 2012-2016, with a trend towards a lower proportion of tinnitus and hearing loss. 4. The number of patients in rhinology has not recovered from the significant decrease in 2012-2016, and rhinitis continues to constitute a significant proportion. 5. The number of patients in laryngology has increased significantly compared to 2012-2016, with a trend towards a less proportion of laryngopharyngitis. Conclusion : The active utilization of diagnostic equipment, further research and promotion of Korean medicine treatment for ophthalmology and otholaryngology diseases are essential for expanding the treatment domain within ophthalmology and otolaryngology of Korean medicine.

Literature Review of AI Hallucination Research Since the Advent of ChatGPT: Focusing on Papers from arXiv (챗GPT 등장 이후 인공지능 환각 연구의 문헌 검토: 아카이브(arXiv)의 논문을 중심으로)

  • Park, Dae-Min;Lee, Han-Jong
    • Informatization Policy
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    • v.31 no.2
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    • pp.3-38
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    • 2024
  • Hallucination is a significant barrier to the utilization of large-scale language models or multimodal models. In this study, we collected 654 computer science papers with "hallucination" in the abstract from arXiv from December 2022 to January 2024 following the advent of Chat GPT and conducted frequency analysis, knowledge network analysis, and literature review to explore the latest trends in hallucination research. The results showed that research in the fields of "Computation and Language," "Artificial Intelligence," "Computer Vision and Pattern Recognition," and "Machine Learning" were active. We then analyzed the research trends in the four major fields by focusing on the main authors and dividing them into data, hallucination detection, and hallucination mitigation. The main research trends included hallucination mitigation through supervised fine-tuning (SFT) and reinforcement learning with human feedback (RLHF), inference enhancement via "chain of thought" (CoT), and growing interest in hallucination mitigation within the domain of multimodal AI. This study provides insights into the latest developments in hallucination research through a technology-oriented literature review. This study is expected to help subsequent research in both engineering and humanities and social sciences fields by understanding the latest trends in hallucination research.

Analysis and implications of North Korea's new strategic drones 'Satbyol-4', 'Satbyol-9' (북한의 신형 전략 무인기 '샛별-4형', '샛별-9형' 분석과 시사점)

  • Kang-Il Seo;Jong-Hoon Kim;Man-Hee Won;Dong-Min Lee;Jae-Hyung Bae;Sang-Hyuk Park
    • The Journal of the Convergence on Culture Technology
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    • v.10 no.2
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    • pp.167-172
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    • 2024
  • In major wars of the 21st century, drones are expanding beyond surveillance and reconnaissance to include land and air as well as sea and underwater for purposes such as precision strikes, suicide attacks, and cognitive warfare. These drones will perform multi-domain operations, and to this end, they will continue to develop by improving the level of autonomy and strengthening scalability based on the High-Low Mix concept. Recently, drones have been used as a major means in major wars around the world, and there seems to be a good chance that they will evolve into game changers in the future. North Korea has also been making significant efforts to operate reconnaissance and attack drones for a long time. North Korea has recently continued to engage in provocations using drones, and its capabilities are gradually becoming more sophisticated. In addition, with the recent emergence of new strategic Drones, wartime and peacetime threats such as North Korea's use of these to secure surveillance, reconnaissance and early warning capabilities against South Korea and new types of provocations are expected to be strengthened. Through this study, we hope to provide implications by analyzing the capabilities of North Korea's strategic Drones, predicting their operation patterns, and conducting active follow-up research on the establishment of a comprehensive strategy, such as our military's drone deployment and counter-drone system solutions.

A study on the diversification of Interpretation according to the Bible didactics by Horst Klaus Berg (Horst Klaus Berg의 성서교수학에 나타난 해석 다양성에 관한 연구)

  • Jeongdo An
    • Journal of Christian Education in Korea
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    • v.77
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    • pp.127-150
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    • 2024
  • This study seeks to shed light on the contributions of Horst Klaus Berg to German Bible didactics, underscoring the pivotal role of diverse interpretative approaches in the teaching and learning of the Bible. In an era where the complexities and intricacies of the Bible present significant challenges to contemporary readers, the prevalence of one-dimensional interpretations further obstructs the pathway to a profound comprehension of the spiritual depth embedded within its texts. By centering on Horst Klaus Berg's influential theories in the field of German Bible didactics, this research delves into the impact of varied biblical interpretations on Christian education. Berg's work is celebrated for its insightful strategies, notably his advocacy for comprehensive interpretative methods such as "Railway Tracks" and "Free-Learning." These approaches seek to reconcile traditional biblical teachings with individual experiences, thereby facilitating a more expansive understanding of the Bible's applicability to modern life. Through a detailed examination of Berg's theory on biblical interpretation, this paper argues that Christian education must prioritize the cultivation of diverse interpretative skills and their practical integration into Bible study. This educational model encourages learners to become active interpreters, capable of discerning the text's deep-seated meanings by relating it to their personal experiences. The study concludes by affirming Berg's delineation of three critical tasks in biblical interpretation: "reciprocal interpretation," "acknowledgment of the biblical texts' diversity," and "free learning." These elements are portrayed as interrelated and essential, reinforcing Berg's proposition that understanding the Bible's complexity and diversity is crucial for advancing Christian education. This paper offers a novel perspective on the significance of embracing multifaceted interpretations within the domain of biblical studies.

Differential expression of tescalcin by modification of promoter methylation controls cell survival in gastric cancer cells

  • Tae Woo Kim;Seung Ro Han;Jong-Tae Kim;Seung-Min Yoo;Myung-Shin Lee;Seung-Hoon Lee;Yun Hee Kang;Hee Gu Lee
    • Oncology Letters
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    • v.41 no.6
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    • pp.3464-3474
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    • 2019
  • The EF-hand calcium binding protein tescalcin (TESC) is highly expressed in various human and mouse cancer tissues and is therefore considered a potential oncogene. However, the underlying mechanism that governs TESC expression remains unclear. Emerging evidence suggests that TESC expression is under epigenetic regulation. In the present study, the relationship between the epigenetic modification and gene expression of TESC in gastric cancer was investigated. To evaluate the relationship between the methylation and expression of TESC in gastric cancer, the methylation status of CpG sites in the TESC promoter was analyzed using microarray with the Illumina Human Methylation27 BeadChip (HumanMethylation27_270596_v.1.2), gene profiles from the NCBI Dataset that revealed demethylated status were acquired, and real-time methylation-specific PCR (MSP) in gastric cancer cells was conducted. In the present study, it was demonstrated that the hypermethylation of TESC led to the downregulation of TESC mRNA/protein expression. In addition, 5-aza-2c-deoxycytidine (5'-aza-dC) restored TESC expression in the tested gastric cancer cells except for SNU-620 cells. ChIP assay further revealed that the methylation of the TESC promoter was associated with methyl-CpG binding domain protein (MBD)1, histone deacetylase (HDAC)2, and Oct-1 and that treatment with 5'-aza-dC facilitated the dissociation of MBD1, HDAC2, and Oct-1 from the promoter of TESC. Moreover, silencing of TESC increased MBD1 expression and decreased the H3K4me2/3 level, thereby causing transcriptional repression and suppression of cell survival in NCI-N87 cells; conversely, overexpression of TESC downregulated MBD1 expression and upregulated the H3K4me2 level associated with active transcription in SNU-638 cells. These results indicated that the differential expression of TESC via the modification status of the promoter and histone methylation controled cell survival in gastric cancer cells. Overall, the present study provided a novel therapeutic strategy for gastric cancer.

A Role for Leu247 Residue within Transmembrane Domain 2 in Ginsenoside-Mediated α7 Nicotinic Acetylcholine Receptor Regulation

  • Lee, Byung-Hwan;Choi, Sun-Hye;Pyo, Mi Kyung;Shin, Tae-Joon;Hwang, Sung-Hee;Kim, Bo-Ra;Lee, Sang-MoK;Lee, Jun-Ho;Lee, Joon-Hee;Lee, Hui Sun;Choe, Han;Han, Kyou-Hoon;Kim, Hyoung-Chun;Rhim, Hyewhon;Yong, Joon-Hwan;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.27 no.5
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    • pp.591-599
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    • 2009
  • Nicotinic acetylcholine receptors (nAChRs) play important roles in nervous system functions and are involved in a variety of diseases. We previously demonstrated that ginsenosides, the active ingredients of Panax ginseng, inhibit subsets of nAChR channel currents, but not ${\alpha}7$, expressed in Xenopus laevis oocytes. Mutation of the highly conserved Leu247 to Thr247 in the transmembrane domain 2 (TM2) channel pore region of ${\alpha}7$ nAChR induces alterations in channel gating properties and converts ${\alpha}7$ nAChR antagonists into agonists. In the present study, we assessed how point mutations in the Leu247 residue leading to various amino acids affect 20(S)-ginsenoside $Rg_3$ ($Rg_3$) activity against the ${\alpha}7$ nAChR. Mutation of L247 to L247A, L247D, L247E, L247I, L247S, and L247T, but not L247K, rendered mutant receptors sensitive to $Rg_3$. We further characterized $Rg_3$ regulation of L247T receptors. We found that $Rg_3$ inhibition of mutant ${\alpha}7$ nAChR channel currents was reversible and concentration-dependent. $Rg_3$ inhibition was strongly voltage-dependent and noncompetitive manner. These results indicate that the interaction between $Rg_3$ and mutant receptors might differ from its interaction with the wild-type receptor. To identify differences in $Rg_3$ interactions between wild-type and L247T receptors, we utilized docked modeling. This modeling revealed that $Rg_3$ forms hydrogen bonds with amino acids, such as Ser240 of subunit I and Thr244 of subunit II and V at the channel pore, whereas $Rg_3$ localizes at the interface of the two wild-type receptor subunits. These results indicate that mutation of Leu247 to Thr247 induces conformational changes in the wild-type receptor and provides a binding pocket for $Rg_3$ at the channel pore.

Cell Migration and Wound Healing Activities of Recombinant Thymosin β-4 Expressed in Escherichia coli (재조합 Thymosin β-4의 세포이동능과 상처치유능)

  • Hong, Kyo-Chang;Choi, Yung Hyun;Kim, Gun-Do;Cha, Hee-Jae;Jeon, Sung-Jong;Nam, Soo-Wan
    • Journal of Life Science
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    • v.32 no.2
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    • pp.135-141
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    • 2022
  • Thymosin β-4 (TB4) is a small peptide composed of 43 amino acids. To obtain sufficient biologically active mouse TB4 economically, we cloned and overexpressed this gene in an Escherichia coli system. With the isopropyl β-D-1-thiogalactopyranoside induction of the E. coli transformant, TB4 fusion protein with intein- and chitin-binding domain was successfully expressed in the soluble fraction within the E. coli cell. The TB4-intein - chitin-binding domain fusion protein was purified from the soluble fraction of E. coli cell lysate. The affinity chromatography with chitin beads and dithiothreitol-mediated intein self-cleavage reaction releases the TB4 peptide into the stripping solution. Sodium dodecyl sulphate - polyacrylamide gel electrophoresis and Western blot analyses were used to confirm that the recombinant TB4 peptide was produced with the expected size of 5 kDa. We found that the recombinant TB4 stimulated cell migration in the transwell plate chamber assay. After 18 hr of the treatment of the recombinant TB4 with 1 ng/ml concentration, the migration of the HT1080 cell was increased by 20% compared with that of the chemically synthesized TB4. The recombinant TB4 was also observed to promote the healing of a wound area in C57BL/6 mice by as high as 35% compared with that of the chemically synthesized TB4. These results suggest that the recombinant TB4 has better biological activity for cell migration and wound healing than that of the chemically synthesized TB4 peptide.

A Study on the Prospect of Implementing a Public Common Practice of Ethics Based upon the Reordering Works of Heaven and Earth (천지공사의 공공윤리 실천전망에 관한 연구)

  • Kim, Yong-Hwan
    • Journal of the Daesoon Academy of Sciences
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    • v.28
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    • pp.37-72
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    • 2017
  • The purpose of this article is to study the prospect of implementing a public common practice of ethics based on the 'Reordering Works of Heaven and Earth.' The 'Reordering Works of Heaven and Earth' demonstrated the prospect of a public common practice of ethics through the shared public action that would connect and mediate both the public domain and the private domain. In addition, the 'Reordering Works of Heaven and Earth' of Gucheon Sangje (九天上帝) provided us with a complete transformation, meaning the opening of a new era, transforming heaven and earth from their state in the Prior World to their optimized state in the Later World. This culminates in a new manifestation of a peaceful world revealed a prosperity and the prospect of common happiness and common order for the public. In addition, the 'Reordering Works of Heaven and Earth' has a public value as a religious culture that responds to social change and social needs. The 'Reordering Works of Heaven and Earth' revealed the prospect of a public common practice of ethics, placed importance on creating a new foundation, and restoring phenomena back to its original order. The 'Reordering Works of Heaven and Earth' presented various multi-faceted, multi-layered outlets of soteriology while exploring solutions to public issues and revealing human dignity. Through the new construction of Heaven and Earth, Gucheon Sangje had intervened in projects for human relief. The public ethical indicators of 'the actor' here are in line with those of the 'Non-action Tao' of Laozi. As the cosmos enters into the new epoch, humans have living together with the previous cosmic principle. Now we can expect the Prior World to open into a different era as humans embrace a cosmic life of 'Non-action Tao.' The active conjunction of the virtues of yin and yang is an idea of horizontal communication related to reordering of the universe. The harmonious union of divine beings and human beings suggests the way of enabling vertical communication. The resolution of grievances for the mutual beneficence of life is an ethics of peace that aims at achieving coexistence and prosperity. The private realization of Tao and the completion of the Tao in the world suggest the prospect of a common practice of ethics as means of implementing human dignity.

A Folksonomy Ranking Framework: A Semantic Graph-based Approach (폭소노미 사이트를 위한 랭킹 프레임워크 설계: 시맨틱 그래프기반 접근)

  • Park, Hyun-Jung;Rho, Sang-Kyu
    • Asia pacific journal of information systems
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    • v.21 no.2
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    • pp.89-116
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    • 2011
  • In collaborative tagging systems such as Delicious.com and Flickr.com, users assign keywords or tags to their uploaded resources, such as bookmarks and pictures, for their future use or sharing purposes. The collection of resources and tags generated by a user is called a personomy, and the collection of all personomies constitutes the folksonomy. The most significant need of the folksonomy users Is to efficiently find useful resources or experts on specific topics. An excellent ranking algorithm would assign higher ranking to more useful resources or experts. What resources are considered useful In a folksonomic system? Does a standard superior to frequency or freshness exist? The resource recommended by more users with mere expertise should be worthy of attention. This ranking paradigm can be implemented through a graph-based ranking algorithm. Two well-known representatives of such a paradigm are Page Rank by Google and HITS(Hypertext Induced Topic Selection) by Kleinberg. Both Page Rank and HITS assign a higher evaluation score to pages linked to more higher-scored pages. HITS differs from PageRank in that it utilizes two kinds of scores: authority and hub scores. The ranking objects of these pages are limited to Web pages, whereas the ranking objects of a folksonomic system are somewhat heterogeneous(i.e., users, resources, and tags). Therefore, uniform application of the voting notion of PageRank and HITS based on the links to a folksonomy would be unreasonable, In a folksonomic system, each link corresponding to a property can have an opposite direction, depending on whether the property is an active or a passive voice. The current research stems from the Idea that a graph-based ranking algorithm could be applied to the folksonomic system using the concept of mutual Interactions between entitles, rather than the voting notion of PageRank or HITS. The concept of mutual interactions, proposed for ranking the Semantic Web resources, enables the calculation of importance scores of various resources unaffected by link directions. The weights of a property representing the mutual interaction between classes are assigned depending on the relative significance of the property to the resource importance of each class. This class-oriented approach is based on the fact that, in the Semantic Web, there are many heterogeneous classes; thus, applying a different appraisal standard for each class is more reasonable. This is similar to the evaluation method of humans, where different items are assigned specific weights, which are then summed up to determine the weighted average. We can check for missing properties more easily with this approach than with other predicate-oriented approaches. A user of a tagging system usually assigns more than one tags to the same resource, and there can be more than one tags with the same subjectivity and objectivity. In the case that many users assign similar tags to the same resource, grading the users differently depending on the assignment order becomes necessary. This idea comes from the studies in psychology wherein expertise involves the ability to select the most relevant information for achieving a goal. An expert should be someone who not only has a large collection of documents annotated with a particular tag, but also tends to add documents of high quality to his/her collections. Such documents are identified by the number, as well as the expertise, of users who have the same documents in their collections. In other words, there is a relationship of mutual reinforcement between the expertise of a user and the quality of a document. In addition, there is a need to rank entities related more closely to a certain entity. Considering the property of social media that ensures the popularity of a topic is temporary, recent data should have more weight than old data. We propose a comprehensive folksonomy ranking framework in which all these considerations are dealt with and that can be easily customized to each folksonomy site for ranking purposes. To examine the validity of our ranking algorithm and show the mechanism of adjusting property, time, and expertise weights, we first use a dataset designed for analyzing the effect of each ranking factor independently. We then show the ranking results of a real folksonomy site, with the ranking factors combined. Because the ground truth of a given dataset is not known when it comes to ranking, we inject simulated data whose ranking results can be predicted into the real dataset and compare the ranking results of our algorithm with that of a previous HITS-based algorithm. Our semantic ranking algorithm based on the concept of mutual interaction seems to be preferable to the HITS-based algorithm as a flexible folksonomy ranking framework. Some concrete points of difference are as follows. First, with the time concept applied to the property weights, our algorithm shows superior performance in lowering the scores of older data and raising the scores of newer data. Second, applying the time concept to the expertise weights, as well as to the property weights, our algorithm controls the conflicting influence of expertise weights and enhances overall consistency of time-valued ranking. The expertise weights of the previous study can act as an obstacle to the time-valued ranking because the number of followers increases as time goes on. Third, many new properties and classes can be included in our framework. The previous HITS-based algorithm, based on the voting notion, loses ground in the situation where the domain consists of more than two classes, or where other important properties, such as "sent through twitter" or "registered as a friend," are added to the domain. Forth, there is a big difference in the calculation time and memory use between the two kinds of algorithms. While the matrix multiplication of two matrices, has to be executed twice for the previous HITS-based algorithm, this is unnecessary with our algorithm. In our ranking framework, various folksonomy ranking policies can be expressed with the ranking factors combined and our approach can work, even if the folksonomy site is not implemented with Semantic Web languages. Above all, the time weight proposed in this paper will be applicable to various domains, including social media, where time value is considered important.