Many annotated long noncoding RNAs (lncRNAs) harbor predicted short open reading frames (sORFs), but the coding capacities of these sORFs and the functions of the resulting micropeptides remain elusive. Here, we report that human lncRNA MIR155HG encodes a 17–amino acid micropeptide, which we termed miPEP155 (P155). MIR155HG is highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacts with the adenosine 5′-triphosphate binding domain of heat shock cognate protein 70 (HSC70), a chaperone required for antigen trafficking and presentation in dendritic cells (DCs). P155 modulates major histocompatibility complex class II–mediated antigen presentation and T cell priming by disrupting the HSC70-HSP90 machinery. Exogenously injected P155 improves two classical mouse models of DC-driven auto inflammation. Collectively, we demonstrate the endogenous existence of a micropeptide encoded by a transcript annotated as “non-protein coding” and characterize a micropeptide as a regulator of antigen presentation and a suppressor of inflammatory diseases.
Interferon-γ-inducible protein 10 (IP-10), or C-X-C motif chemokine (CXCL10), is a small cytokine belonging to the non-ELR CXC chemokine family. By binding to its specific receptor CXCR3, IP-10 recruits activated CXCR3+ T cells to the liver parenchyma and plays a pivotal role in liver disease initiation and progression. IP-10 is mainly secreted by hepatocytes and liver sinusoidal endothelium. Different IP-10 forms exert different functions: long-length IP-10 directs CXCR3+ T cell migration and is associated with inflammation, while short IP-10 is a CXCR3 antagonist, thereby playing protective role in liver injury. IP-10 levels are positively associated with the severity of liver inflammation, fibrosis stage and acute graft rejection. High IP-10 levels are closely related to anti-HCV therapy failure. Thus, IP-10 may be both a potential prognostic tool and a therapeutic target for the treatment of patients with HCV or HIV/HCV co-infection. The purpose of this review is to highlight the growing advances in basic knowledge and clinical interest of IP-10 in liver disease.
Hepatitis C virus (HCV) infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.
BackgroundPsoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic acids, a group of compounds with anti-inflammatory and anti-cancer properties. Target identification of AKBA and metabolomics analysis of psoriasis helped to elucidate the molecular mechanism underlying its effect, and provide new target(s) to treat the disease.MethodsTo explore the targets and molecular mechanism of AKBA, we performed affinity purification, metabolomics analysis of HaCaT cells treated with AKBA, and epidermis of imiquimod (IMQ) induced mouse model of psoriasis and psoriasis patients.FindingsAKBA directly interacts with methionine adenosyltransferase 2A (MAT2A), inhibited its enzyme activity, decreased level of S-adenosylmethionine (SAM) and SAM/SAH ratio, and reprogrammed one‑carbon metabolism in HaCaT cells. Untargeted metabolomics of epidermis showed one‑carbon metabolism was activated in psoriasis patients. Topical use of AKBA improved inflammatory phenotype of IMQ induced psoriasis-like mouse model. Molecular docking and site-directed mutagenesis revealed AKBA bound to an allosteric site at the interface of MAT2A dimer.InterpretationOur study extends the molecular mechanism of AKBA by revealing a new interacting protein MAT2A. And this leads us to find out the dysregulated one‑carbon metabolism in psoriasis, which indicates the therapeutic potential of AKBA in psoriasis.FundThe National Natural Science Foundation, the National Program on Key Basic Research Project, the Shanghai Municipal Commission, the Leading Academic Discipline Project of the .
Callus culture has, to date, been reported only in a few species of Narcissus. We used anthers of Chinese narcissus (Narcissus tazetta L. var. chinensis Roem) as explants for callus induction and plant regeneration. A high percentage of anthers at the early- to mid-uninucleate microspore stage were responsive on the basal MS medium supplemented with 0.5-1 mg l(-1) 2,4-dichlorophenoxyacetic acid and 0.5-2 mg l(-1) 6-benzyladenine under dark conditions. Calli were initiated from anther connective tissue or anther wall tissue, and no division of microspores occurred during callus formation, as determined by histological observation. Using 20 random amplified polymorphic DNA primers, we verified the genetic integrity of the anther-derived plants of Chinese narcissus with respect to the donor plants. These results suggest that anther culture in vitro can provide an efficient new micropropagation technique for Chinese narcissus as well as a new strategy for in vitro mass propagation of other daffodils.
Background Integrated information on the global prevalence and incidence of bullous pemphigoid (BP) is lacking. Objective To estimate the incidence and prevalence of BP in a systematic review and meta‐analysis. Methods Observational studies were included by using databases of Medline, EMBASE, and Cochrane Library. Subgroup analysis was by continent, age, sex, and country income level. Random‐effects model was used. Between‐study heterogeneity was assessed using the I2 statistic. Results The global incidence was 0.0419 per 1000 person‐years (95% CI: 0.0414–0.0424). The incidence was 0.047 per 1000 person‐years (95% CI: 0.0462–0.0477), 0.0419 per 1000 person‐years (95% CI: 0.0411–0.0426), 0.0072 per 1000 person‐years (95% CI: 0.0067–0.0078), 0.003 per 1000 person‐years (95% CI: 0.0023–0.0039) in North America, Europe, Asia, and Africa, respectively; 0.0202 per 1000 person‐years (95% CI: 0.0196–0.0208) and 0.0181 per 1000 person‐years (95% CI: 0.0175–0.0188) females and males; 0.001 per 1000 person‐years (95% CI: 0.001–0.001), 0.002 per 1000 person‐years (95% CI: 0.001–0.002), 0.004 per 1000 person‐years (95% CI: 0.004–0.004); 0.007 per 1000 person‐years (95% CI: 0.007–0.008), 0.011 per 1000 person‐years (95% CI: 0.011–0.012), 0.017 per 1000 person‐years (95% CI: 0.015–0.018) for age <50, 50–59, 60–69, 70–79, 80–89, and ≥90 years; 0.0038 per 1000 person‐years (95% CI: 0.0036–0.004112) (I2 = 99%, p < .05) and 0.0456 per 1000 person‐years (95% CI: 0.0450–0.0462) (I2 = 100%, p < .05). The pooled clinic‐based prevalence was 0.79% (95% CI: 0.75%–0.84%), 1.13% (95% CI: 1.06%–1.21%), 0.21% (95% CI: 0.17%–0.26%), and 0.13% (95% CI: 0.1%–0.15%) for Asia, Africa, and Europe. Conclusions This study identified the global incidence and prevalence of BP in terms of spatial and population distributions and among various income level. A relatively higher incidence was in Europe, females, older people, and high‐income level country. The prevalence was higher in Asia. These findings should be interpreted with caution due to high heterogeneity of included studies.
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