• BMB Reports
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• v.51 no.5
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7415-7423
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• 2015

Chronic myeloid leukemia (CML) is a stem cell disorder characterized by unrestricted proliferation of the myeloid series that occurs due to the BCR-ABL fusion oncogene as a result of reciprocal translocation t(9;22) (q34;q11). This discovery has made this particular domain a target for future efforts to cure CML. Imatinib revolutionized the treatment options for CML and gave encouraging results both in case of safety as well as tolerability profile as compared to agents such as hydroxyurea or busulfan given before Imatinib. However, about 2-4% of patients show resistance and mutations have been found to be one of the reasons for its development. European Leukemianet gives recommendations for BCR-ABL mutational analysis along with other tyrosine kinase inhibitors (TKIs) that should be administered according to the mutations harbored in a patient. The following overview gives recommendations for monitoring patients on the basis of their mutational status.

• The Plant Pathology Journal
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• v.36 no.3
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• pp.204-217
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• 2020

In nature, plants are always under the threat of pests and diseases. Pathogenic bacteria are one of the major pathogen types to cause diseases in diverse plants, resulting in negative effects on plant growth and crop yield. Chemical bactericides and antibiotics have been used as major approaches for controlling bacterial plant diseases in the field or greenhouse. However, the appearance of resistant bacteria to common antibiotics and bactericides as well as their potential negative effects on environment and human health demands bacteriologists to develop alternative control agents. Bacteriophages, the viruses that can infect and kill only target bacteria very specifically, have been demonstrated as potential agents, which may have no negative effects on environment and human health. Many bacteriophages have been isolated against diverse plant-pathogenic bacteria, and many studies have shown to efficiently manage the disease development in both controlled and open conditions such as greenhouse and field. Moreover, the specificity of bacteriophages to certain bacterial species has been applied to develop detection tools for the diagnosis of plant-pathogenic bacteria. In this paper, we summarize the promising results from greenhouse or field experiments with bacteriophages to manage diseases caused by plant-pathogenic bacteria. In addition, we summarize the usage of bacteriophages for the specific detection of plant-pathogenic bacteria.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.5
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• pp.132-138
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• 2021

Artificial intelligence technology sheds light on new ways of innovating acupuncture research. As acupoint selection is specific to target diseases, each acupoint is generally believed to have a specific indication. However, the specificity of acupoint selection may be not always same with the specificity of acupoint indication. In this review, we propose that the specificity of acupoint indication can be inferred from clinical data using reverse inference. Using forward inference, the prescribed acupoints for each disease can be quantified for the specificity of acupoint selection. Using reverse inference, targeted diseases for each acupoint can be quantified for the specificity of acupoint indication. It is noteworthy that the selection of an acupoint for a particular disease does not imply the acupoint has specific indications for that disease. Electronic medical record includes various symptoms and chosen acupoint combinations. Data mining approach can be useful to reveal the complex relationships between diseases and acupoints from clinical data. Combining the clinical information and the bodily sensation map, the spatial patterns of acupoint indication can be further estimated. Interoperable medical data should be collected for medical knowledge discovery and clinical decision support system. In the era of artificial intelligence, machine learning can reveal the associations between diseases and prescribed acupoints from large scale clinical data warehouse.

• IMMUNE NETWORK
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• v.23 no.2
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• pp.12.1-12.17
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• 2023

Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4⁺ T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4⁺ T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.11.1-11.26
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• 2022

When epithelial cells are exposed to potentially threatening external stimuli such as allergens, bacteria, viruses, and helminths, they instantly produce "alarmin" cytokines, namely, IL-33, IL-25, and TSLP. These alarmins alert the immune system about these threats, thereby mobilizing host immune defense mechanisms. Specifically, the alarmins strongly stimulate type-2 immune cells, including eosinophils, mast cells, dendritic cells, type-2 helper T cells, and type-2 innate lymphoid cells. Given that the alarm-raising role of IL-33, IL-25, and TSLP was first detected in allergic and infectious diseases, most studies on alarmins focus on their role in these diseases. However, recent studies suggest that alarmins also have a broad range of effector functions in other pathological conditions, including psoriasis, multiple sclerosis, and cancer. Therefore, this review provides an update on the epithelium-derived cytokines in both allergic and non-allergic diseases. We also review the progress of clinical trials on biological agents that target the alarmins and discuss the therapeutic potential of these agents in non-allergic diseases.

• BMB Reports
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• v.42 no.11
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• pp.737-742
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• 2009

Hypoxia-inducible factor-$1{\alpha}/{\beta}$ (HIF-$1{\alpha}/{\beta}$) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-$1{\alpha}$ has been noted as an effective therapeutic target for ischemic diseases such as myocardiac infarction, stroke and cancer. By using a yeast two-hybrid system and a random peptide library, we found a 16-mer peptide named F29 that directly interacts with the bHLH-PAS domain of HIF-$1{\alpha}$. We found that F29 facilitates the interaction of the HIF-$1{\alpha/\beta}$ heterodimer with its target DNA sequence, hypoxia-responsive element (HRE). The transient transfection of an F29-expressing plasmid increases the expression of both an HRE-driven luciferase gene and the endogenous HIF-1 target gene, vascular endothelial growth factor (VEGF). Taken together, we conclude that F29 increases the DNA-binding ability of HIF-$1{\alpha}$, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-$1{\alpha}$ and increases its activity.

• Journal of Gastric Cancer
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• v.18 no.1
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• pp.1-19
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• 2018

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant diseases. While continued efforts have been focused on GC treatment, the introduction of trastuzumab marked the beginning of a new era of target-specific treatments. Considering the diversity of mutations in GC, satisfactory results obtained from various target-specific therapies were expected, yet most of them were unsuccessful in controlled clinical trials. There are several possible reasons underlying the failures, including the absence of patient selection depending on validated predictive biomarkers, the inappropriate combination of drugs, and tumor heterogeneity. In contrast to targeted agents, immuno-oncologic agents are designed to regulate and boost immunity, are not target-specific, and may overcome tumor heterogeneity. With the successful establishment of predictive biomarkers, including Epstein-Barr virus pattern, microsatellite instability status, and programmed death-ligand 1 (PD-L1) expression, as well as ideal combination regimens, a new frontier in the immuno-oncology of GC treatment is on the horizon. Since the field of immuno-oncology has witnessed innovative, practice-changing successes in other cancer types, several trials on GC are ongoing. Among immuno-oncologic therapies, immune checkpoint inhibitors are the mainstay of clinical trials performed on GC. In this article, we review target-specific agents currently used in clinics or are undergoing clinical trials, and highlight the future clinical application of immuno-oncologic agents in inoperable GC.

• Toxicological Research
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• v.24 no.2
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• pp.101-107
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• 2008

Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

• The Journal of Pediatrics of Korean Medicine
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• v.33 no.3
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• pp.82-102
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• 2019

Objectives The purpose of this study is to investigate clinical studies on the efficacy and safety of herbal medicine inhalation therapy in children by analyzing recent randomized controlled trials conducted in China. Methods We searched the clinical studies from the China Academic Journal (CAJ) in China National Knowledge Infrastructure (CNKI) using a by key word '霧化吸入' and specific criteria from 1st January 2010 to 2nd July 2019. Data regarding years of publication, demographic information, target diseases or symptoms, treatment methods, outcome measure, results and adverse events are collected for this study. Results Total of 44 randomized controlled trials were selected and analyzed. Respiratory diseases and symptoms (84.1%) were the most frequent target diseases that herbal medicine inhalation therapy was used. Acute stomatitis was another disease state that the therapy was used. In most of the studies, the herbal medicine inhalation in children showed significant efficacies. The most commonly used herbal medicines were Ephedrae Herba (麻黃), Lonicera Flos (金銀花), Armeniacae Semen (杏仁), Glycyrrhizae Radix et Rhizoma (甘草), Scutellaria Radix (黃芩), Forsythia Fructus (連翹) etc. Hardly any adverse effects were reported from the trials selected. Conclusions Based on the results of the clinical studies from China, herbal medicine inhalation therapy in children can be an effective and safe option for treatment and symptom improvement.