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https://www.readbyqxmd.com/read/29441299/livedo-racemosa-reticulated-ulcerations-panniculitis-and-violaceous-plaques-in-a-46-year-old-woman
#1
Alfredo Agulló, Brian Hinds, Mónica Larrea, Ignacio Yanguas
Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) that has conventional cutaneous manifestations of DM, but paradoxically, little or no muscle involvement. In 2005, a novel antibody was described in association with CADM - anti-melanoma differentiation-associated gene 5 (anti-MDA5). Patients with this serologic marker have a characteristic mucocutaneous phenotype consisting of skin ulceration among other signs. We describe the case of a 46-year-old woman with CADM, elevated anti-MDA5 autoantibodies, and unusual clinical features (livedo racemosa, florid acral edema) among the classical phenotype of MDA5 DM (arthralgias, ulcerations, panniculitis) and classical DM lesions (Gottron papules, heliotrope rash)...
January 2018: Indian Dermatology Online Journal
https://www.readbyqxmd.com/read/29429386/r516q-mutation-in-melanoma-differentiation-associated-protein-5-mda5-and-its-pathogenic-role-towards-rare-singleton-merton-syndrome-a-signature-associated-molecular-dynamics-study
#2
P Raghuraman, C Sudandiradoss
Singleton Merton syndrome, a critical and rare multifactorial disorder that is closely linked to R516Q mutation in MDA5 protein associated with an enhanced interferon response in the affected individual. In the present study, we provide conclusive key evidence on R516Q mutation and their connectivity towards sequence-structural basis dysfunction of MDA5 protein. Among the various mutations, we found R516Q is the most pathogenic mutation based on mutational signature Q-A-[RE]-G-R-[GA]-R-A-[ED]-[DE]-S-[ST]-Y-[TSAV]-L-V designed from our work...
February 11, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29427062/identification-of-new-type-i-interferon-stimulated-genes-and-investigation-of-their-involvement-in-ifn-%C3%AE-activation
#3
Xiaolin Zhang, Wei Yang, Xinlu Wang, Xuyuan Zhang, Huabin Tian, Hongyu Deng, Liguo Zhang, Guangxia Gao
Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production...
February 9, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29425484/sort-your-self-out
#4
Carolina Uggenti, Yanick J Crow
Discrimination between viral and self-derived nucleic acid species is crucial in maintaining effective antiviral immunity whilst avoiding autoinflammation. Ahmad et al. and Chung et al. delineate the consequences of MDA5 gain of function and loss of ADAR1 activity, highlighting the blurring of the concept of self and non-self when considering endogenous retroelements.
February 8, 2018: Cell
https://www.readbyqxmd.com/read/29417209/rapidly-progressive-interstitial-lung-disease-due-to-anti-mda5-antibodies-without-skin-involvement-a-case-report-and-literature-review
#5
REVIEW
Juan González-Moreno, Manuel Raya-Cruz, Ines Losada-Lopez, Ana Paula Cacheda, Cristina Oliver, Bartomeu Colom
Anti-MDA5 antibodies have been strongly associated with rapidly progressive interstitial lung disease (RP-ILD) in dermatomyositis (DM) patients, especially in the clinically amyopathic subset (CADM). We present a case of anti-MDA5 antibody-associated RP-ILD in a patient with arthritis but with no other clinical signs suggestive of DM or CADM successfully treated with a combination of cyclophosphamide, cyclosporine and corticoids. A review of the literature was also done. Despite its rarity, anti-MDA5 antibody-associated ILD should be suspected in cases of RP-ILD even without other signs of DM or CADM as prompt and aggressive treatment could improve prognosis...
February 7, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29415054/chitosan-oligosaccharide-ameliorates-acute-lung-injury-induced-by-blast-injury-through-the-ddah1-adma-pathway
#6
Yun-En Liu, Cang-Ci Tong, Yu-Biao Zhang, Pei-Fang Cong, Xiu-Yun Shi, Ying Liu, Lin Shi, Zhou Tong, Hong-Xu Jin, Ming-Xiao Hou
OBJECTIVE: To investigate the protective effect of chitosan oligosaccharide (COS) on acute lung injury (ALI) caused by blast injury, and explore possible molecular mechanisms. METHODS: A mouse model of blast injury-induced ALI was established using a self-made explosive device. Thirty mice were randomly assigned to control, ALI and ALI + COS groups. An eight-channel physiological monitor was used to determine the mouse physiological index. Enzyme linked immunosorbent assay was used to measure serum inflammatory factors...
2018: PloS One
https://www.readbyqxmd.com/read/29407895/innate-antiviral-immune-response-against-infectious-bronchitis-virus-and-involvement-of-prostaglandin-e2-in-the-uterine-mucosa-of-laying-hens
#7
M Elhamouly, T Terada, T Nii, N Isobe, Y Yoshimura
Infectious bronchitis virus (IBV) is an enveloped RNA virus that causes deformities in eggshells. The aim of this study was to investigate the innate immune response to IBV, and to determine whether prostaglandin (PG) E2, which is synthesized during inflammation, is involved in the innate immune response in the uterine mucosa. The effects of intra-oviductal inoculation with attenuated IBV (aIBV) on the expression of viral RNA recognition receptors and innate antiviral factors were examined by real-time PCR and immunohistochemistry, and on PGE2 levels by ELISA...
January 11, 2018: Theriogenology
https://www.readbyqxmd.com/read/29407574/pathogenicity-of-duck-hepatitis-a-virus-type-3-and-innate-immune-responses-of-the-ducklings-to-virulent-dhav-3
#8
Xuelian Zhang, Chong Cao, Zhehui Qu, Wenjing Zhang, Yue Liu, Haihui Qi, Chunxue Hao, Wenlong Zhang, Mingchun Gao, Junwei Wang, Bo Ma
Duck virus hepatitis caused by duck hepatitis A virus (DHAV) is an acute and contagious disease. To better understand the pathogenic mechanism of DHAV-3 in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DHAV-3 could infect many tissues, leading to pathological lesions, especially on the livers and spleen, and the host immune responses are activated in infection. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the livers and spleen, and antiviral innate immune response was established, but not sufficient to restrict the virus replication of lethal dose...
January 26, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29397456/immune-responses-of-mature-chicken-bone-marrow-derived-dendritic-cells-infected-with-newcastle-disease-virus-strains-with-differing-pathogenicity
#9
Bin Xiang, Wenxian Zhu, Yaling Li, Pei Gao, Jianpeng Liang, Di Liu, Chan Ding, Ming Liao, Yinfeng Kang, Tao Ren
Infection of chickens with virulent Newcastle disease virus (NDV) is associated with severe pathology and increased morbidity and mortality. The innate immune response contributes to the pathogenicity of NDV. As professional antigen-presenting cells, dendritic cells (DCs) play a unique role in innate immunity. However, the contribution of DCs to NDV infection has not been investigated in chickens. In this study, we selected two representative NDV strains, i.e., the velogenic NDV strain Chicken/Guangdong/GM/2014 (GM) and the lentogenic NDV strain La Sota, to investigate whether NDVs could infect LPS-activated chicken bone-derived marrow DCs (mature chicken BM-DCs)...
February 3, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29395576/reduced-hmgb1-suppresses-poly-i-c-induced-inflammation-in-keratinocytes
#10
Hideki Mori, Masamoto Murakami, Teruko Tsuda, Kenji Kameda, Ryo Utsunomiya, Kana Masuda, Ken Shiraishi, Xiuju Dai, Mikiko Tohyama, Hiroki Nakaoka, Koji Sayama
BACKGROUND: High mobility group box 1 (HMGB1) is a nuclear protein that stabilizes DNA and facilitates gene transcription. Additionally, cell stress or death induces the release of HMGB1 outside the cell membrane, where HMGB1 functions as an alarmin, causing an inflammatory response in combination with other cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs). OBJECTIVE: To evaluate the effect of reduced-HMGB1 (previously termed chemoattractive-HMGB1) on polyinosine-polycytidylic acid [poly(I:C)]-induced inflammation in normal human keratinocytes (NHKs)...
January 29, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29395326/breaching-self-tolerance-to-alu-duplex-rna-underlies-mda5-mediated-inflammation
#11
Sadeem Ahmad, Xin Mu, Fei Yang, Emily Greenwald, Ji Woo Park, Etai Jacob, Cheng-Zhong Zhang, Sun Hur
Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral dsRNA sensor that induces antiviral immune response. Using a newly developed RNase-protection/RNA-seq approach, we demonstrate here that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNAs because of its limited filament formation on imperfect duplexes, AGS variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNAs...
January 8, 2018: Cell
https://www.readbyqxmd.com/read/29395325/human-adar1-prevents-endogenous-rna-from-triggering-translational-shutdown
#12
Hachung Chung, Jorg J A Calis, Xianfang Wu, Tony Sun, Yingpu Yu, Stephanie L Sarbanes, Viet Loan Dao Thi, Abigail R Shilvock, H-Heinrich Hoffmann, Brad R Rosenberg, Charles M Rice
Type I interferon (IFN) is produced when host sensors detect foreign nucleic acids, but how sensors differentiate self from nonself nucleic acids, such as double-stranded RNA (dsRNA), is incompletely understood. Mutations in ADAR1, an adenosine-to-inosine editing enzyme of dsRNA, cause Aicardi-Goutières syndrome, an autoinflammatory disorder associated with spontaneous interferon production and neurologic sequelae. We generated ADAR1 knockout human cells to explore ADAR1 substrates and function. ADAR1 primarily edited Alu elements in RNA polymerase II (pol II)-transcribed mRNAs, but not putative pol III-transcribed Alus...
January 12, 2018: Cell
https://www.readbyqxmd.com/read/29395320/pattern-recognition-receptor-mrna-expression-and-cytokine-and-granzyme-levels-in-hiv-infected-individuals-with-neurotuberculosis
#13
Deepashri Rao, Ravi Vasanthapuram, P Satishchandra, Anita Desai
Neurotuberculosis is one of the commonest HIV-associated opportunistic infections (OI) of the CNS. Cross-talk between HIV, Mycobacterium tuberculosis and host immune responses may alter expression of pattern recognition receptors (PRRs), thereby affecting cytokine profiles and functional responses. We examined PRR mRNA expression and cytokine and granzyme levels in HIV infected individuals with neurotuberculosis and found significant downregulation of TLR9 and increased MDA5 expression compared to healthy subjects...
January 27, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29380533/analysis-of-anti-melanoma-differentiation-associated-gene-5-antibody-in-hong-kong-chinese-patients-with-idiopathic-inflammatory-myopathies-diagnostic-utility-and-clinical-correlations
#14
Ho So, Ricky W-K Ip, Victor T-L Wong, Ronald M-L Yip
AIM: To compare the prevalence of the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) in Hong Kong Chinese patients with dermatomyositis (DM) and polymyositis (PM); in addition, to examine the association of anti-MDA5 Ab and the clinical characteristics of these patients. METHODS: Twenty consecutive existing patients with DM being followed up at the Rheumatology Clinic of Kwong Wah Hospital, Hong Kong were recruited. Twenty patients with PM were recruited from the same clinic as the controls...
January 30, 2018: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29367762/suppression-of-sting-signaling-through-epigenetic-silencing-and-missense-mutation-impedes-dna-damage-mediated-cytokine-production
#15
Hiroyasu Konno, Shota Yamauchi, Anders Berglund, Ryan M Putney, James J Mulé, Glen N Barber
The production of cytokines in response to DNA-damage events may be an important host defense response to help prevent the escape of pre-cancerous cells. The innate immune pathways involved in these events are known to be regulated by cellular molecules such as stimulator of interferon genes (STING), which controls type I interferon and pro-inflammatory cytokine production in response to the presence of microbial DNA or cytosolic DNA that has escaped from the nucleus. STING signaling has been shown to be defective in a variety of cancers, such as colon cancer and melanoma, actions that may enable damaged cells to escape the immunosurveillance system...
January 25, 2018: Oncogene
https://www.readbyqxmd.com/read/29351913/the-rig-i-like-receptor-lgp2-inhibits-dicer-dependent-processing-of-long-double-stranded-rna-and-blocks-rna-interference-in-mammalian-cells
#16
Annemarthe G van der Veen, Pierre V Maillard, Jan Marten Schmidt, Sonia A Lee, Safia Deddouche-Grass, Annabel Borg, Svend Kjær, Ambrosius P Snijders, Caetano Reis E Sousa
In vertebrates, the presence of viral RNA in the cytosol is sensed by members of the RIG-I-like receptor (RLR) family, which signal to induce production of type I interferons (IFN). These key antiviral cytokines act in a paracrine and autocrine manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein products restrict viral entry, replication and budding. ISGs include the RLRs themselves: RIG-I, MDA5 and, the least-studied family member, LGP2. In contrast, the IFN system is absent in plants and invertebrates, which defend themselves from viral intruders using RNA interference (RNAi)...
January 19, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29344607/bosentan-for-cutaneous-ulcers-in-anti-mda5-dermatomyositis
#17
Andrea Combalia, Priscila Giavedoni, Lorena Tamez, Josep M Grau-Junyent, Jose M Mascaró
No abstract text is available yet for this article.
January 17, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29338781/correlation-between-disease-activity-and-serum-ferritin-in-clinically-amyopathic-dermatomyositis-with-rapidly-progressive-interstitial-lung-disease-a-case-report
#18
Kazuhiro Yamada, Kazuhisa Asai, Atsuko Okamoto, Tetsuya Watanabe, Hiroshi Kanazawa, Mai Ohata, Masahiko Ohsawa, Kazuto Hirata
BACKGROUND: Clinically amyopathic dermatomyositis with anti-Melanoma Differentiation-Associated gene 5 (MDA5) antibody often presents with severe interstitial lung disease. Although serum ferritin level is known to reflect interstitial lung disease activity, there are few case reports describing this association. CASE PRESENTATION: A 58-year-old man was referred to our outpatient clinic with a 3-week history of cough and respiratory distress. He had erythema over the V area of the neck and a Gottron's sign...
January 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29331962/splicing-variant-of-wdfy4-augments-mda5-signalling-and-the-risk-of-clinically-amyopathic-dermatomyositis
#19
Yuta Kochi, Yoichiro Kamatani, Yuya Kondo, Akari Suzuki, Eiryo Kawakami, Ryosuke Hiwa, Yukihide Momozawa, Manabu Fujimoto, Masatoshi Jinnin, Yoshiya Tanaka, Takashi Kanda, Robert G Cooper, Hector Chinoy, Simon Rothwell, Janine A Lamb, Jiří Vencovský, Heřman Mann, Koichiro Ohmura, Keiko Myouzen, Kazuyoshi Ishigaki, Ran Nakashima, Yuji Hosono, Hiroto Tsuboi, Hidenaga Kawasumi, Yukiko Iwasaki, Hiroshi Kajiyama, Tetsuya Horita, Mariko Ogawa-Momohara, Akito Takamura, Shinichiro Tsunoda, Jun Shimizu, Keishi Fujio, Hirofumi Amano, Akio Mimori, Atsushi Kawakami, Hisanori Umehara, Tsutomu Takeuchi, Hajime Sano, Yoshinao Muro, Tatsuya Atsumi, Toshihide Mimura, Yasushi Kawaguchi, Tsuneyo Mimori, Atsushi Takahashi, Michiaki Kubo, Hitoshi Kohsaka, Takayuki Sumida, Kazuhiko Yamamoto
OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases in which both genetic and environmental factors play important roles. To identify genetic factors of IIM including polymyositis, dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first genome-wide association study for IIM in an Asian population. METHODS: We genotyped and tested 496 819 single nucleotide polymorphism for association using 576 patients with IIM and 6270 control subjects...
January 13, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29329033/onjisaponin-b-prevents-cognitive-impairment-in-a-rat-model-of-d-galactose-induced-aging
#20
Gaowen Li, Jimian Yu, Ling Zhang, Yong Wang, Chuang Wang, Qun Chen
In this study, we investigated the potential effect of onjisaponin B (OB) on aging rats induced by D-gal (D-galactose). Sub-acute aging model was established in rats by the subcutaneous injection of D-gal (120 mg/kg) for 42 days, accompanied with OB (10, 20 mg/kg, p.o.) or normal saline intervention for 28 days since the 14th day after the beginning of D-gal stimulation. Morris water maze test and step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The superoxidase dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-px) contents in hippocampus were measured by according kits, respectively...
January 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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