miR-1246 inhibits NFATc1 phosphorylation and regulates Th17 cell activation in the pathogenesis of severe alopecia areata

Si-si Qi,Ying Miao,You-yu Sheng,Rui-ming Hu,Jun Zhao,Qin-ping Yang 대한피부과학회 2023 Annals of Dermatology Vol.35 No.1

Background: We found microRNA (miR)-1246 to be significantly differentially expressedbetween severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ Tcells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistryassays. Peripheral CD4+ T cells from the AA patients were transfectedwith lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis wereused to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclearreceptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylatedNFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA wasused to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantlyincreased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cellsbut not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltratinginflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA,overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1,ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in theCD4+IL-17+ cells proportion and the IL-17F level. Conclusion: miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may bebeneficial in the severe AA treatment.

Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going

Chen Liang,Si Shi,Qingcai Meng,Dingkong Liang,Shunrong Ji,Bo Zhang,Yi Qin,Jin Xu,Quanxing Ni,Xianjun Yu 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.

The Influence of Changing PV Array Interconnections under a Non-uniform Irradiance

Ding, Kun,Feng, Li,Qin, Si-Yu,Mao, Jing,Zhang, Jing-Wei,Wang, Xiang,Peng, Tao,Zhai, Quan-Xin The Korean Institute of Power Electronics 2016 JOURNAL OF POWER ELECTRONICS Vol.16 No.2

Usually, the output characteristics of a photovoltaic (PV) array are significantly affected by non-uniform irradiance which is caused by ambient obstacles, clouds, orientations, tilts, etc. Some local maximum power points (LMPP) in the current-voltage (I-V) curves of a PV array can result in power losses of the array. However, the output power at the global maximum power point (GMPP) is different in different interconnection schemes in a PV array. Therefore, based on the theoretical analysis and mathematical derivation of different topological structures of a PV array, this paper investigated the output characteristics of dual series PV arrays with different interconnections. The proposed mathematical models were also validated by experimental results. Finally, this paper also concluded that in terms of performance, the total cross tied (TCT) interconnection was not always the optimal structure, especially in a dual series PV array. When one of the PV modules was severely mismatched, the TCT worked worse than the series parallel (SP) structure. This research can provide guidance for switching the interconnection to gain the greatest energy yield in a changeable- structure PV system.

The Influence of Changing PV Array Interconnections under a Non-uniform Irradiance

Kun Ding,Li Feng,Si-Yu Qin,Jing Mao,Jing-Wei Zhang,Xiang Wang,Tao Peng,Quan-Xin Zhai 전력전자학회 2016 JOURNAL OF POWER ELECTRONICS Vol.16 No.2

Usually, the output characteristics of a photovoltaic (PV) array are significantly affected by non-uniform irradiance which is caused by ambient obstacles, clouds, orientations, tilts, etc. Some local maximum power points (LMPP) in the current-voltage (I-V) curves of a PV array can result in power losses of the array. However, the output power at the global maximum power point (GMPP) is different in different interconnection schemes in a PV array. Therefore, based on the theoretical analysis and mathematical derivation of different topological structures of a PV array, this paper investigated the output characteristics of dual series PV arrays with different interconnections. The proposed mathematical models were also validated by experimental results. Finally, this paper also concluded that in terms of performance, the total cross tied (TCT) interconnection was not always the optimal structure, especially in a dual series PV array. When one of the PV modules was severely mismatched, the TCT worked worse than the series parallel (SP) structure. This research can provide guidance for switching the interconnection to gain the greatest energy yield in a changeable- structure PV system.

Gut microbiota metabolic characteristics in coronary artery disease patients with hyperhomocysteine

Tian Ran,Liu Hong-Hong,Feng Si-Qin,Wang Yi-Fei,Wang Yi-Yang,Chen Yu-Xiong,Wang Hui,Zhang Shu-Yang 한국미생물학회 2022 The journal of microbiology Vol.60 No.4

Hyperhomocysteine (HHcy) is known as a risk factor for coronary artery disease (CAD). Despite the knowledge that gut microbiota related metabolism pathway shares metabolites with that of Hcy, little has been shown concerning the association between HHcy and gut microbiota. To explore their relationship in the context of CAD, 105 patients and 14 healthy controls were recruited from one single medical center located in Beijing, China. Their serum and fecal samples were collected, with multi-omics analyses performed via LC/MS/ MS and 16S rRNA gene V3-V4 region sequencing, respectively. Participants from the prospective cohort were divided into CAD, CAD & HHcy and healthy controls (HC) groups based on the diagnosis and serum Hcy concentration. The results revealed significant different metabolic signatures between CAD and CAD & HHcy groups. CAD patients with HHcy suffered a heavier atherosclerotic burden compared to CAD patients, and the difference was closely associated to betaine-homocysteine S-methyltransferase (BHMT)-related metabolites and trimethylamine N-oxide (TMAO)-related metabolites. Dimethylglycine (DMG) exhibited a strong positive correlation with serum total Hcy (tHcy), and TMAO and trimethylysine (TML) were associated with heavier atherosclerotic burden. Multiple other metabolites were also identified to be related to distinct cardiovascular risk factors. Additionally, Clostridium cluster IV and Butyricimonas were enriched in CAD patients with elevated tHcy. Our study suggested that CAD patients with elevated tHcy were correlated with higher atherosclerotic burden, and the impaired Hcy metabolism and cardiovascular risk were closely associated with BHMT-related metabolites, TMAO-related metabolites and impaired gut microbiota homeostasis.