Riiseirwin6568
Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription.
Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. A-1210477 Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4weeks and 7weeks, respectively. Importantly, except for ~ 1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300.
Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.
Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.Kidney diseases pose a threat to human health due to their rising incidence and fatality rate. In preclinical and clinical studies, it has been acknowledged that mesenchymal stem cells (MSCs) are effective and safe when used to treat kidney diseases. MSCs play their role mainly by secreting trophic factors and delivering extracellular vesicles (EVs). The genetic materials and proteins contained in the MSC-derived EVs (MSC-EVs), as an important means of cellular communication, have become a research focus for targeted therapy of kidney diseases. At present, MSC-EVs have shown evident therapeutic effects on acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), and atherosclerotic renovascular disease (ARVD); however, their roles in the transplanted kidney remain controversial. This review summarises the mechanisms by which MSC-EVs treat these diseases in animal models and proposes certain problems, expecting to facilitate corresponding future clinical practice.
Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC).
Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Western blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in HCC cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Flow cytometry was used to analyze cell cycle distribution and apoptosis rate. A xenograft model was established to study the effect of PCSK9 on HCC growth in vivo. TUNEL and immunofluorescence assays were used to detect cell apoptosis.
High expression of PCSK9 in tumor tissues was related to microvascular invasion (p = 0.036) and large tumor size (p = 0.001) in HCC patients. Overall survival and disease-free survival after surgery were poor in patients with high expression of PCSK9 (p = 0.035 and p = 0.007, respectively). In vivo and in vitro experiments showed that PCSK9 promoted the growth of HCC by inhibiting cell apoptosis. A mechanistic study revealed that PCSK9 increases FASN expression, thereby inhibiting apoptosis of HCC cells via the Bax/Bcl-2/Caspase9/Caspase3 pathway.
PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.
PCSK9 expression level in HCC is an indicator of poor prognosis for patients with HCC. FASN-mediated anti-apoptosis plays an important role in PCSK9-induced HCC progression.
Although Japanese radish (Raphanus sativus L.) is a common Japanese ingredient, there are few reports of IgE-mediated immediate food allergy caused by Japanese radish.
A 48-year-old woman developed urticarial lesions on her hands after grating Japanese radish and also developed lip edema and oral itching when she ate a salad composed of raw Japanese radishes. Skin prick testing was positive to extract of grated Japanese radish. Moreover, immunoblotting analysis showed IgE reactivity in the patient's serum to a single band at the 18kDa in grated Japanese radish, suggesting that the heat-labile 18kDa protein of raw Japanese radish may be a radish-specific antigen.
To the best of our knowledge, this is the first case report of a patient with hand urticaria, lip angioedema, and oropharyngeal pruritus to raw Japanese radish through IgE-mediated immediate allergic reaction.
To the best of our knowledge, this is the first case report of a patient with hand urticaria, lip angioedema, and oropharyngeal pruritus to raw Japanese radish through IgE-mediated immediate allergic reaction.
Transient ischemic attack (TIA) is considered to be an important risk factor for the development of ischemic stroke and requires complete etiopathogenic evaluation and prompt initiation of secondary prevention treatment. In addition, an accurate differential diagnosis should be performed in order to exclude other disorders mimicking TIA.
In this case report, we describe the clinical and neuroimaging evaluation and the differential diagnosis of a patient with suspected crescendo TIAs.
A 79-year-old man presented with recurrent episodes of right-sided numbness over the past 7 months, despite different single and dual antiplatelet therapies that were sequentially prescribed for suspected TIAs. Brain MRI revealed cortical superficial siderosis, symmetrical periventricular leukoencephalopathy and enlarged perivascular spaces. Cerebral amyloid angiopathy was considered in the differential diagnosis of the patient. Antiplatelet withdrawal was recommended and led to complete remission of the patient's transient focal neurological episodes (TFNE) that were initially misdiagnosed as TIAs.
