• Title/Summary/Keyword: molecular pathogenesis

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Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis

  • Son, Young-Ok;Chun, Jang-Soo
    • BMB Reports
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    • v.51 no.4
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    • pp.165-166
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    • 2018
  • Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability with a large socioeconomic cost. OA is a whole-joint disease characterized by cartilage destruction, synovial inflammation, osteophyte formation, and subchondral bone sclerosis. To date, however, no effective disease-modifying therapies for OA have been developed. The estrogen-related receptors (ERRs), a family of orphan nuclear receptor transcription factors, are composed of $ERR{\alpha}$, $ERR{\beta}$, and $ERR{\gamma}$, which play diverse biological functions such as cellular energy metabolism. However, the role of ERRs in OA pathogenesis has not been studied yet. Among the ERR family members, $ERR{\gamma}$ is markedly upregulated in human and various models of mouse OA cartilage. Adenovirus-mediated overexpression of $ERR{\gamma}$ in the mouse knee joint tissue caused OA pathogenesis. Additionally, cartilage-specific $ERR{\gamma}$ transgenic (Tg) mice exhibited enhanced experimental OA. Consistently, $ERR{\gamma}$ in articular chondrocytes directly caused expression of matrix metalloproteinase (MMP) 3 and MMP13, which play a crucial role in cartilage destruction. In contrast, genetic ablation of Esrrg or shRNA-mediated Esrrg silencing in the joint tissues abrogated experimental OA in mice. These results collectively indicated that $ERR{\gamma}$ is a novel catabolic regulator of OA pathogenesis and can be used as a therapeutic target for OA.

Recent Advances in Molecular Basis of Lung Aging and Its Associated Diseases

  • Kang, Min-Jong
    • Tuberculosis and Respiratory Diseases
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    • v.83 no.2
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    • pp.107-115
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    • 2020
  • Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.

Anti-inflammatory Action of Calorie Restriction for Life-Prolongation: A Possible Mechanism

  • Chung, Hae-Young
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.173-174
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    • 2002
  • Oxidative modification of cellular structures and functions by redox imbalance is the basis of the current oxidative stress hypothesis of aging. The experimental support for this hypothsis has been generated from recent molecular probing on the interrelation between the age-related functional impairments and the pathogenesis. (omitted)

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Middle East Respiratory Syndrome-Coronavirus Infection into Established hDPP4-Transgenic Mice Accelerates Lung Damage Via Activation of the Pro-Inflammatory Response and Pulmonary Fibrosis

  • Kim, Ju;Yang, Ye Lin;Jeong, Yongsu;Jang, Yong-Suk
    • Journal of Microbiology and Biotechnology
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    • v.30 no.3
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    • pp.427-438
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    • 2020
  • Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

Identification of Glycine max Genes Expressed in Response to Soybean mosaic virus Infection

  • Jeong, Rae-Dong;Lim, Won-Seok;Kwon, Sang-Wook;Kim, Kook-Hyung
    • The Plant Pathology Journal
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    • v.21 no.1
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    • pp.47-54
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    • 2005
  • Identification of host genes involved in disease progresses and/or defense responses is one of the most critical steps leading to the elucidation of disease resistance mechanisms in plants. Soybean mosaic virus (SMV) is one of the most prevalent pathogen of soybean (Glycine max). Although the soybeans are placed one of many important crops, relatively little is known about defense mechanism. In order to obtain host genes involved in SMV disease progress and host defense especially for virus resistance, two different cloning strategies (DD RT-PCR and Subtractive hybridization) were employed to identify pathogenesis- and defenserelated genes (PRs and DRs) from susceptible (Geumjeong 1) and resistant (Geumjeong 2) cultivars against SMV strain G7H. Using these approaches, we obtained 570 genes that expressed differentially during SMV infection processes. Based upon sequence analyses, differentially expressed host genes were classified into five groups, i.e. metabolism, genetic information processing, environmental information processing, cellular processes and unclassified group. A total of 11 differentially expressed genes including protein kinase, transcription factor, other potential signaling components and resistant-like gene involved in host defense response were selected to further characterize and determine expression profiles of each selected gene. Functional characterization of these genes will likely facilitate the elucidation of defense signal transduction and biological function in SMV-infected soybean plants.

Prevalence and Molecular Characterization of Echinococcus granulosus Sensu Stricto in Northern Xinjiang, China

  • Guo, Baoping;Zhang, Zhuangzhi;Zheng, Xueting;Guo, Yongzhong;Guo, Gang;Zhao, Li;Cai, Ren;Wang, Bingjie;Yang, Mei;Shou, Xi;Zhang, Wenbao;Jia, Bin
    • Parasites, Hosts and Diseases
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    • v.57 no.2
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    • pp.153-159
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    • 2019
  • Echinococcus granulosus is an important zoonotic parasite globally causing cystic echinococcosis (CE) in humans and animals. In this study, prevalence of CE and variation of cox1 gene sequence were analyzed with isolates E. granulosus collected from different areas in northern Xinjiang, China. The survey showed that 3.5% of sheep and 4.1% of cattle were infected with CE. Fragment of cox1 was amplified from all the positive sheep and cattle samples by PCR. In addition, 26 positive samples across the 4 areas were included. The isolates were all E. granulosus sensu stricto (s.s.) containing 15 haplotypes (Hap1-15), and clustered into 2 genotypes, G1 (90.1%, 91/101) and G3 (9.9%, 10/101). Hap1 was the most common haplotype (48.5%, 49/101). Hap9 were found in humans samples, indicating that sheep and cattle reservoir human CE. It is indicate that E. granulosus may impact on control of CE in livestock and humans in the region.

Biological function of nonxpressor of pathogenesis-related genes 1 (NPR1) in response to biotic and abiotic stresses (생물학 및 비생물학적 스트레스 반응에서의 NPR1 기능 고찰)

  • Cheong, Mi Sun;Kim, Sewon;Yun, Dae-Jin
    • Journal of Plant Biotechnology
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    • v.43 no.3
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    • pp.281-292
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    • 2016
  • Plants can recognize and respond in various ways to diverse environmental stresses, including pathogenic microorganisms, salt, drought, and low temperature. Salicylic acid (SA) is one phytohormone that plays important roles in the regulation of plant growth and development. Nonexpressor of pathogenesis-related genes 1 (NPR1) was originally identified as a core protein that could function as a transcriptional co-regulator and SA receptor during systemic acquired resistance (SAR), a plant immune response that could activate PR genes after pre-exposure of a pathogen. Although the function of NPR1 in plant defense response and the role of SA hormone in the regulation of plant physiological processes have been well characterized, the biological role of NPR1 in plant abiotic stress responses is largely unknown. In this review, we will summarize and discuss the current understanding of NPR1 function in response to plant environmental stresses.

Hepatitis Delta Virus Large Antigen Sensitizes to TNF-α-Induced NF-κB Signaling

  • Park, Chul-Yong;Oh, Sang-Heun;Kang, Sang Min;Lim, Yun-Sook;Hwang, Soon B.
    • Molecules and Cells
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    • v.28 no.1
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    • pp.49-55
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    • 2009
  • Hepatitis delta virus (HDV) infection causes fulminant hepatitis and liver cirrhosis. To elucidate the molecular mechanism of HDV pathogenesis, we examined the effects of HDV viral proteins, the small hepatitis delta antigen (SHDAg) and the large hepatitis delta antigen (LHDAg), on $NF-{\kappa}B$ signaling pathway. In this study, we demonstrated that $TNF-{\alpha}-induced$ $NF-{\kappa}B$ transcriptional activation was increased by LHDAg but not by SHDAg in both HEK293 and Huh7 cells. Furthermore, LHDAg promoted TRAF2-induced $NF-{\kappa}B$ activation. Using coimmunoprecipitation assays, we demonstrated that both SHDAg and LHDAg interacted with TRAF2 protein. We showed that isoprenylation of LHDAg was not required for the increase of $NF-{\kappa}B$ activity. We further showed that only LHDAg but not SHDAg increased the $TNF-{\alpha}-mediated$ nuclear translocation of p65. This was accomplished by activation of $I{\kappa}B_{\alpha}$ degradation by LHDAg. Finally, we demonstrated that LHDAg augmented the COX-2 expression level in Huh7 cells. These data suggest that LHDAg modulates $NF-{\kappa}B$ signaling pathway and may contribute to HDV pathogenesis.

Performance of DNA Methylation on the Molecular Pathogenesis of Helicobacter pylori in Gastric Cancer; targeted therapy approach

  • Vahidi, Sogand;Mirzajani, Ebrahim;Norollahi, Seyedeh Elham;Aziminezhad, Mohsen;Samadani, Ali Akbar
    • Journal of Pharmacopuncture
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    • v.25 no.2
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    • pp.88-100
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    • 2022
  • Gastric cancer (GC) is a significant cause of cancer mortality which has led to focused exploration of the pathology of GC. The advent of genome-wide analysis methods has made it possible to uncover genetic and epigenetic fluctuation such as abnormal DNA methylation in gene promoter regions that is expected to play a key role in GC. The study of gastric malignancies requires an etiological perspective, and Helicobacter pylori (H. pylori) was identified to play a role in GC. H. pylori infection causes chronic inflammation of the gastric epithelium causing abnormal polyclonal methylation, which might raise the risk of GC. In the last two decades, various pathogenic factors by which H. pylori infection causes GC have been discovered. Abnormal DNA methylation is triggered in several genes, rendering them inactive. In GC, methylation patterns are linked to certain subtypes including microsatellite instability. Multiple cancer-related processes are more usually changed by abnormal DNA methylation than through mutations, according to current general and combined investigations. Furthermore, the amount of acquired abnormal DNA methylation is heavily linked to the chances of developing GC. Therefore, we investigated abnormal DNA methylation in GC and the link between methylation and H. pylori infection.

A review of the latest research on Ganoderma boninense

  • Su-Han LEE;Su-Han LEE
    • The Korean Journal of Food & Health Convergence
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    • v.9 no.2
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    • pp.1-6
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    • 2023
  • As oil palm trees are an important economic source in many countries, particularly in Southeast Asia and Africa, the study of Ganoderma boninense is crucial for the sustainability of the oil palm industry. This study aims to understand the biology and ecology of the fungus, its pathogenesis, and the impact it has on oil palm trees. This knowledge can be used to develop management strategies to mitigate the damage caused by the fungus, such as the use of resistant varieties, chemical and biological control methods, and cultural practices. This study is to ensure the long-term productivity and sustainability of the oil palm industry. The main method of recent academic studies on this pathogen is molecular biology, with a focus on genetic analysis and functional genomics. Researchers have used techniques such as PCR, DNA sequencing, and transcriptomics to identify genes and pathways involved in pathogenesis and better understand the fungus's interactions with its host plant. Other methods used in recent studies include biochemical analysis, microscopy, and phytohormonal assays to investigate the biochemistry and physiology of the interaction between G. boninense and oil palm. This study is intended to provide implications from a new perspective by organizing and integrating studies on Ganoderma boninense.