1.miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease.
Man LUO ; Yayan PANG ; Junjie LI ; Lilin YI ; Bin WU ; Qiuyun TIAN ; Yan HE ; Maoju WANG ; Lei XIA ; Guiqiong HE ; Weihong SONG ; Yehong DU ; Zhifang DONG
Acta Pharmaceutica Sinica B 2024;14(2):635-652
Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.
2.Horseshoe kidney transplantation: a report of 2 cases
Qiong CHEN ; Yehong YAN ; Zeyu CAI ; Jialiang HAN ; Xingjian ZHANG ; Qi XIAO
Chinese Journal of Organ Transplantation 2024;45(11):807-810
To explore the feasibility and experience of kidney transplantation with horseshoe kidney as donor kidney. The horseshoe kidney donated by a brain dead donor was obtained by in-situ perfusion and whole piece incision. After methylene blue staining was injected into the inferior pole artery of the kidney and separated from the isthmus along the edge of the stained site, two kidney donors were divided into two recipients with successful implantation. After renal transplantation, the blood supply of the two donor kidneys was good. During the perioperative period, there was no bleeding or urine leakage. Postoperative ureteral obstruction occurred in one recipient. After the double J-tube drainage was ineffective, autologous ureter was anastomoted with the renal pelvis of the transplanted kidney. Up to now, the renal function of two recipients remained stable. According to literature analysis, kidney transplantation with well-functioning horseshoe kidney as donor kidney is safe and feasible, but its postoperative complication rate is higher than that of conventional kidney transplantation.
3.Dietary intervention for the treatment of psoriasis
Liping JIN ; Wu ZHU ; Yan LU ; Panpan LIU ; Minjia TAN ; Ying WANG ; Jing YANG ; Licong XU ; Kun HU ; Yehong KUANG
Chinese Journal of Dermatology 2023;56(4):357-360
This review summarizes dietary characteristics of patients with psoriasis, discusses effects of gluten-free diet, Mediterranean diet and dietary intervention-induced weight loss on psoriasis, and analyzes the efficacy of dietary supplements in the treatment of psoriasis, such as fish oil, vitamin D, vitamin B12, selenium, and probiotics.
4.Penicillium marneffei infection after renal transplantation: one case report
Zeyu CAI ; Yehong YAN ; Qi XIAO ; Xingjian ZHANG ; Chen ZHOU ; Jialiang HAN ; Qiong CHEN
Chinese Journal of Organ Transplantation 2023;44(7):428-432
Clinical data were retrospectively reviewed for one case of penicillium marneffei infection after renal transplantation (RT) to explore a proper management of peniciliosis marneffei (PSM)transplantation.This case had a history of pulmonary tuberculosis and underwent RT due to uremia.After discharging, postoperative recovery was excellent.Recurrent cough occurred at Month 7 post-operation.Fiberoptic bronchoscopy and pulmonary CT indicated a possibility of pulmonary tuberculosis.However, a definite diagnosis of PSM was confirmed by next generation sequencing (NGS) and pathogenic bacteria culture of alveolar lavage fluid.After adjusting immunosuppressive agents and regular antifungal treatment with voriconazole, respiratory symptoms improved and pulmonary CT hinted at a resorption of lesion.Features of pulmonary CT and bronchoscopic examination were nearly similar to those of tuberculosis.Thus early bacterium culture and NGS may aid an definite diagnosis.Voriconazole is an effective treatment of the disease.
5.Analysis of anticancer compound,indole-3-carbinol,in broccoli using a new ultrasound-assisted dispersive-filter extraction method based on poly(deep eutectic solvent)-graphene oxide nanocomposite
Yanan YUAN ; Huanhuan CHEN ; Yehong HAN ; Fengxia QIAO ; Hongyuan YAN
Journal of Pharmaceutical Analysis 2022;12(2):301-307
Indole-3-carbinol(I3C),an important anticancer compound found in broccoli,has attracted considerable attention.The rapid extraction and accurate analysis of I3C in the pharmaceutical industry in broccoli is challenging as I3C is unstable at low pH and high temperature.In this study,a rapid,accurate,and low-cost ultrasound-assisted dispersive-filter extraction(UADFE)technique based on poly(deep eutectic solvent)-graphene oxide(PDES-GO)adsorbent was developed for the isolation and analysis of I3C in broccoli for the first time.PDES-GO with multiple adsorption interactions and a fast mass transfer rate was synthesized to accelerate adsorption and desorption.UADFE was developed by combining dispersive solid-phase extraction(DSPE)and filter solid-phase extraction(FSPE)to realize rapid extraction and separation.Based on the above two strategies,the proposed PDES-GO-UADFE method coupled with high-performance liquid chromatography(HPLC)allowed the rapid(15-16 min),accurate(84.3%-96.4%),and low-cost(adsorbent:3.00 mg)analysis of I3C in broccoli and was superior to solid-phase extraction,DSPE,and FSPE methods.The proposed method showed remarkable linearity(r=0.9998;range:0.0840-48.0 μg/g),low limit of quantification(0.0840 μg/g),and high precision(relative standard deviation≤5.6%).Therefore,the PDES-GO-UADFE-HPLC method shows significant potential in the field of pharmaceutical analysis for the separation and analysis of anti-cancer compounds in complex plant samples.
6.Preoperative prediction of microvascular invasion in patients with hepatocellular carcinoma based on SII, AFP and tumor diameter
Huangbin ZHANG ; Yehong YAN ; Hao WAN ; Zuochuan DING ; Chen ZHOU ; Jiansheng XIAO
Chinese Journal of Hepatobiliary Surgery 2021;27(10):733-738
Objective:To study the predictive value of systemic immune-inflammation index (SII), alpha-fetoprotein (AFP) and tumor diameter on microvascular invasion (MVI) in patients with resectable hepatocellular carcinoma (HCC), with an aim to establish a preoperative prediction model.Methods:The clinical data of 283 patients who underwent hepatectomy at the First Affiliated Hospital of Nanchang University from September 2017 to September 2020 were retrospectively analyzed. In the 283 patients with HCC who were included into this study, 249 were males and 34 were females, aged (53.7±11.0) years. Using postoperative pathology findings, these patients were divided into two groups: the MVI negative group ( n=140) and the MVI positive group ( n=143). Correlation between MVI and related indicators was analyzed using logistic regression analysis. The prediction model of MVI was then established by selecting independent risk factors. Univariate and multivariate analysis of recurrence-free survival (RFS) were performed using the Cox proportional hazards regression model. Results:Multivariate logistic regression analysis showed that AFP>400 ng/ml ( OR=2.304, 95% CI: 1.329-3.995, P=0.003), SII>376.30×10 9/L ( OR=2.249, 95% CI: 1.299-3.894, P=0.004) and tumor diameter>5 cm ( OR=2.728, 95% CI: 1.587-4.687, P<0.001) were independent risk factors for MVI. The Cox proportional hazards regression model showed that AFP ( HR=1.663, 95% CI: 1.063-2.602, P=0.026) and SII ( HR=1.851, 95% CI: 1.173-2.920, P=0.008) were independent risk factors for RFS in HCC patients. The sensitivity and specificity of the model based on SII, AFP and tumor diameter were 59.4% and 75.7%, respectively. Conclusions:SII, AFP and tumor diameter were closely related to occurrence of MVI in patients with HCC. AFP and SII were independent prognostic factors of RFS. This prediction model has certain predictive values for occurrence of MVI and prognosis of HCC patients.
7.Human parvovirus B19 infection-associated anemia after liver transplantation: three case reports with a literature review
Shitao ZHAO ; Yehong YAN ; Huangbin ZHANG ; Zide CHEN ; Chen ZHOU ; Hao WAN ; Qi XIAO ; Jiansheng XIAO
Chinese Journal of Organ Transplantation 2021;42(11):675-679
Objective:To explore the diagnosis and treatment of pure red cell aplastic anemia (PRCA) caused by parvovirus B19 (HPV-B19)infection after liver transplantation (LT).Methods:Three adult PRCA patients caused by parvovirus B19 infection after LT were reviewed retrospectively.The relevant literatures were collected to sort out the detection methods and treatment of parvovirus B19 infection after LT.Results:All three patients received liver transplantation due to end-stage liver disease with massive intraoperative blood transfusion and smooth postoperative recovery.Severe anemia occurred at 1-2 Months after discharge.Hemorrhagic anemia was excluded after re-admission and PRCA was diagnosed by bone marrow aspiration and next generation sequencing (NGS). After tapering the intensity of immunosuppressive therapy, intravenous immunoglobulin (IVIG) was administered for 7-10 days and hemoglobin soon normalized.A review of 15 recent literatures on HPV-B19 infection after LT revealed that the diagnosis and treatment of parvovirus B19 infection after LT gradually were became same.Conclusions:HPV-B19 infection causes PRCA after LT in adults.Diagnosing with NGS, intravenous injection of immunoglobulin and modification of immunosuppressant regimen may achieve excellent therapeutic efficacies.
8.One case of gastrointestinal mucor infection secondary to severe pneumonia after renal transplantation and literature review
Yuan DU ; Jianfeng LI ; Yehong YAN ; Jiansheng XIAO ; Hao WAN ; Feixiang WU ; Huangbing ZHANG
Chinese Journal of Organ Transplantation 2020;41(5):301-304
Objective:To explore the clinical diagnosis and treatment of invasive gastrointestinal fungal infection plus pulmonary infection after renal transplantation.Methods:Clinical data were analyzed retrospectively for one patient with invasive fungal infection plus pulmonary infection after renal transplantation. The middle-aged female recipient underwent allogeneic kidney transplantation due to end-stage uremia. After successful kidney transplantation, there was postprandial epigastric pain not relieved by proton pump inhibitor. Gastroscopy after admission suggested that the nature of gastric mucosal lesions was to be determined. Pathological examination and special staining confirmed mucor.Results:After clarifying her conditions, the doses of such immunosuppression as tacrolimus, mycophenolate mofetil and prednisone were tapered and discontinued when necessary and using amphotericin B liposome plus posaconazole alleviated the digestive tract symptoms. Chest tightness, fever, shortness of breath after activities hinted at pulmonary infection after renal transplantation. Treatment was guided by the results of sputum culture.Conclusions:Mucor infection is rare in digestive tract complicated with pulmonary infection after renal transplantation. Clinicians should actively search for etiological evidence, seek multidisciplinary consultations for a definite diagnosis and provide empirical anti-infection treatments. Due attention is to be paid for double infection caused by anti-infection treatments and anti-infection treatment strategy should be timely adjusted and the dosage of immunosuppressant based upon immune monitoring.
10.Effect of methotrexate on regulation for the number of regulatory T cells and expression of Foxp3 in psoriasis.
Yehong KUANG ; Heng ZHANG ; Wu ZHU ; Lisha WU ; Wangqing CHEN ; Yan LU ; Qunshi QIN ; Xuekun JIA ; Liqiu LIAO
Journal of Central South University(Medical Sciences) 2018;43(8):835-842
To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.
Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes.
Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05).
Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.
Adjuvants, Immunologic
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pharmacology
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Aminoquinolines
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pharmacology
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Animals
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Case-Control Studies
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Female
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Forkhead Transcription Factors
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metabolism
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Humans
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Imiquimod
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Immunosuppressive Agents
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administration & dosage
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pharmacology
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Lymphocyte Count
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Methotrexate
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administration & dosage
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pharmacology
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Mice
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Mice, Inbred BALB C
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Psoriasis
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drug therapy
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immunology
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metabolism
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pathology
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RNA, Messenger
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metabolism
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Random Allocation
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Spleen
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cytology
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T-Lymphocytes, Regulatory
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cytology
;
drug effects
;
metabolism

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