• BMB Reports
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• v.51 no.7
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• pp.315-316
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• 2018

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) system can be used as a tool to correct pathological mutations or modulate gene expression levels associated with pathogenesis of human diseases. Owing to well-established local administration methods including intravitreal and subretinal injection, it is relatively easy to administer therapeutic genome engineering machinery to ocular tissues for treating retinal diseases. In this context, we have investigated the potential of in vivo genome engineering as a therapeutic approach in the form of ribonucleoprotein or CRISPR packaged in viral vectors. Major issues in therapeutic application of genome engineering include specificity and efficacy according to types of CRISPR system. In addition to previous platforms based on ribonucleoprotein and CRISPR-associated protein 9 derived from Campylobacter jejuni, we evaluated the therapeutic effects of a CRISPR RNA-guided endonuclease derived from Lachnospiraceae bacterium ND2006 (LbCpf1) in regulating pathological angiogenesis in an animal model of wet-type age-related macular degeneration. LbCpf1 targeting Vegfa or Hif1a effectively disrupted the expression of genes in ocular tissues, resulting in suppression of choroidal neovascularization. It was also notable that there were no significant off-target effects in vivo.

• BMB Reports
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• v.41 no.4
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• pp.278-286
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• 2008

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.

• BMB Reports
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• v.49 no.8
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• pp.405-413
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• 2016

Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders.

• BMB Reports
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• v.46 no.6
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• pp.295-304
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• 2013

Extracellular acidification occurs not only in pathological conditions such as inflammation and brain ischemia, but also in normal physiological conditions such as synaptic transmission. Acid-sensing ion channels (ASICs) can detect a broad range of physiological pH changes during pathological and synaptic cellular activities. ASICs are voltage-independent, proton-gated cation channels widely expressed throughout the central and peripheral nervous system. Activation of ASICs is involved in pain perception, synaptic plasticity, learning and memory, fear, ischemic neuronal injury, seizure termination, neuronal degeneration, and mechanosensation. Therefore, ASICs emerge as potential therapeutic targets for manipulating pain and neurological diseases. The activity of these channels can be regulated by many factors such as lactate, $Zn^{2+}$, and Phe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides by interacting with the channel's large extracellular loop. ASICs are also modulated by G protein-coupled receptors such as CB1 cannabinoid receptors and 5-$HT_2$. This review focuses on the physiological roles of ASICs and the molecular mechanisms by which these channels are regulated.

• BMB Reports
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• v.48 no.10
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• pp.549-558
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• 2015

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

• BMB Reports
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• v.41 no.8
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• pp.555-559
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• 2008

Reactive oxygen species (ROS) are generated in mammalian cells via both enzymatic and non-enzymatic mechanisms. Although certain ROS production pathways are required for the performance of specific physiological functions, excessive ROS generation is harmful, and has been implicated in the pathogenesis of a number of diseases. Among the ROS-producing enzymes, NADPH oxidase is widely distributed among mammalian cells, and is a crucial source of ROS for physiological and pathological processes. Reactive oxygen species are also generated by arachidonic acid (AA) metabolites, which are released from membrane phospholipids via the activity of cytosolic phospholipase $A_2$ ($cPLA_2$). In this study, we describe recent studies concerning the generation of ROS by AA metabolites. In particular, we have focused on the manner in which AA metabolism via lipoxygenase (LOX) and LOX metabolites contributes to ROS generation. By elucidating the signaling mechanisms that link LOX and LOX metabolites to ROS, we hope to shed light on the variety of physiological and pathological mechanisms associated with LOX metabolism.

• The Journal of Internal Korean Medicine
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• v.39 no.6
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• pp.1085-1104
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• 2018

Objectives: The purpose of this research is to investigate recent clinical studies of Intestinal Metaplasia (IM) based on a search of the China National Knowledge Infrastructure (CNKI). Methods: We investigated recent clinical studies of Oriental medicine therapies in traditional Chinese medical journals for IM through a CNKI search. 20 clinical articles published from 2010 to 2016 were analyzed. This study examined the authors, publication years, types of studies, criteria for diagnosis and evaluation, periods, purposes of study and articles classified by methods of treatment. Results: Most of articles were classified as randomized controlled trial. IM was diagnosed using gastroscopy, pathological examination and clinical symptoms in a high proportion of articles. The criteria for evaluation most frequently used were the effective ratios of clinical symptoms, gastroscopy and pathological tests. The methods of treatment in all studies were Chinese herb medicine. Acupuncture, acupoint injection therapy, and embedding therapy were also used in several studies. Conclusion: In this study, the Chinese treatment for IM was markedly effective. To improve the treatment of IM in Korea, many clinical studies and case reports are required, based on Chinese medicine.

• Journal of Trauma and Injury
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• v.37 no.1
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• pp.89-96
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• 2024

The indications for total hip replacement are increasing and not limited to osteoarthritis. Total hip replacement may also be done for trauma and pathological fractures in patients otherwise physiologically fit and active. This trend has led to an inevitable rise in complications such as periprosthetic femoral fracture. Periprosthetic femoral fracture can be challenging due to poor bone quality, osteoporosis, and stress fractures. We present a case of periprosthetic femoral fracture in a 71-year-old woman with some components of an atypical femoral fracture. The fracture was internally fixed but was subsequently complicated by infection, implant failure needing revision, and later stress fracture. She was on a bisphosphonate after her index total hip replacement surgery for an impending pathological left proximal femur fracture, and this may have caused the later stress fracture. Unfortunately, she then experienced implant breakage (nonunion), which was treated with a biplanar locking plate and bone grafting. The patient finally regained her premorbid mobility 13 months after the last surgery and progressed satisfactorily towards bony union.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1907-1910
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• 2012

Background: Breast cancer is the most prevalent cancer and the fifth cause of cancer death in Iranian women. Early detection and treatment are important for appropriate management of this disease. Mammography and ultrasonography are used for screening and evaluation of symptomatic cases and the main diagnostic test for breast cancer is pathological. In this study we evaluated mammography and ultrasonography as diagnostic tools. Methods: In this cross-sectional study 384 mammography and ultrasonography reports for 255 women were assessed, divided into benign and malignant groups. Suspected cases were referred for pathology evaluation. The radiologic and pathologic reports were compared and also comparison was performed based on age groups (more and less than 50 years old), history of breastfeeding and gravidity. Statistical analysis was performed by SPSS. Results: The mean ages of malignant and benign cases were $49{\pm}11.6$ and $43{\pm}11.2$ years, respectively. Sensitivity and specificity for mammography were 73% and 45%, respectively. Sensitivity and specificity for ultrasonography were 69% and 49%, respectively. There were statistical differences between specificity of mammography in patients based on factors such as history of gravidity, breastfeeding and sensitivity in patients equal or more than 50 years old and less. Conclusion: Factors affecting different results in mammography and ultrasonography reports were classified into three groups, consisting of skill, experience and training of medical staff, and setting of instruments. It is recommended that health managers in developing countries pay attention the quality of setting and man power more than current status. Policy-makers and managers must establish guidelines regarding breast imaging in Iran.

• BMB Reports
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• v.35 no.1
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• pp.28-40
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• 2002

Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-${\kappa}B$ activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-${\kappa}B$ and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which mayor may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-${\kappa}B$ controls apoptosis.