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1.
Life Sci ; : 119233, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600863

RESUMO

Aim Increasing evidence demonstrated circular RNAs (circRNAs) are involved in the development of various diseases, including sepsis-induced AKI. Although CIRC-Ttc3 has been proved to regulate cardiac function after myocardial infarction, its role in sepsis-induced AKI remains unclear. MATERIALS AND METHODS: The AKI rat model was firstly induced by sepsis through cecal ligation puncture (CLP). Serum levels of creatinine, BUN, NGAL, TNF-α, IL-6, SOD, MDA and IL-1ß were measured through appropriate kits. The pathological alteration and renal microvascular permeability in renal tissues were determined by HE staining and Evans Blue assays. Cell apoptosis was detected by TUNEL assay. The expression levels of CIRC-Ttc3, miR-148a, TNF-α, IL-1ß and iNOS in rats' renal samples were tested by qRT-PCR or/and western blot. The binding ability between CIRC-Ttc3 and miR-148a was evaluated through luciferase reporter, RIP and RNA pull-down assays. KEY FINDINGS: Kidney injury was found in CLP-treated rats. CIRC-Ttc3 expression was down-regulated, and upregulation of CIRC-Ttc3 improved inflammatory responses and oxidative stress in AKI rats. Mechanismly, CIRC-Ttc3 was confirmed to bind to and negatively regulate miR-148a. Further rescue assays revealed that overexpression of miR-148a rescued the improvement of CIRC-Ttc3 on sepsis-induced AKI. Then, it was illustrated that CIRC-Ttc3 regulated Rcan2 expression by binding to miR-148a. Finally, knockdown of Rcan2 reversed the effects of miR-148a inhibition on sepsis-induced AKI. SIGNIFICANCE: CIRC-Ttc3 relieved inflammation and oxidative stress through regulating the miR-148a/Rcan2 axis in rats with AKI induced by sepsis. Therefore, CIRC-Ttc3 may be a potential therapeutic target for sepsis-induced AKI.

2.
FASEB J ; 35(2): e21367, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33508160

RESUMO

Millions of human deaths occur annually due to chronic kidney disease, caused by diabetic kidney disease (DKD). Despite having effective drugs controlling the hyperglycemia and high blood pressure, the incidence of DKD is increasing, which indicates the need for the development of novel therapies to control DKD. In this article, we discussed the recent advancements in the basic innate immune mechanisms in renal tissues triggered under the diabetes environment, leading to the pathogenesis and progression of DKD. We also summarized the currently available innate immune molecules-targeting therapies tested against DKD in clinical and preclinical settings, and highlighted additional drug targets that could potentially be employed for the treatment of DKD. The improved understanding of the disease pathogenesis may open avenues for the development of novel therapies to rein in DKD, which consequently, can reduce morbidity and mortality in humans in the future.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33420914

RESUMO

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an ongoing global pandemic of coronavirus disease 2019 (COVID-19). The challenges associated with imaging infected patients have resulted, to date, in a paucity of metabolic imaging studies of patients with severe COVID-19 infection. Furthermore, it remains unclear if any abnormal metabolic events are taking place in patients who have recovered from COVID-19. PURPOSE: To use [18F] fluorodeoxyglucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) to measure metabolic activity in inflamed organs of patients convalescing post severe COVID-19 infection. MATERIALS AND METHODS: A prospective study was performed in seven convalescing patients who were recovering from severe COVID-19 infection in February 2020. Prior to [18F] FDG PET/CT, all patients had received two consecutive negative results of real-time reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 nucleic acid. Clinical intake including symptoms, treatment, laboratory test results, and follow-up was performed. The PET/CT images of COVID-19 patients were compared to a control group of patients that were matched for age and sex. RESULTS: Residual pulmonary lesions were present in all patients and maximum standard uptake value (SUVmax), average standard uptake value (SUVavg), maximum CT intensity (CTmax), and average CT intensity (CTavg) were all significantly greater than in the control group (p < 0.01 for all). In addition, SUVmax and SUVavg were significantly greater in the mediastinal lymph node and liver, and SUVmax was significantly greater in the spleen, of COVID-19 patients compared with controls (p < 0.05 for all). For the spleen, SUVmax (r2 = 0.863, p = 0.003) and SUVavg (r2 = 0.797, p = 0.007) were significantly correlated with blood lymphocyte count, and which was below the normal range in five of the seven (71.4%) patients convalescing post severe COVID-19 infection. CONCLUSION: [18F] FDG PET/CT quantitative analysis has shown that significant inflammation remained in lungs, mediastinal lymph nodes, spleen, and liver after two consecutive negative RT-PCR tests in patients convalescing post severe COVID-19 infection.

5.
Bioorg Chem ; : 104561, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33349457

RESUMO

Although targeted therapy for renal cell carcinoma (RCC) has achieved good therapeutic effects in clinic, a considerable number of patients develop drug resistance over time. So, there is still an urgent need to develop new drugs for RCC treatment. As LSD1 is considered as a promising drug target in diverse cancers, including RCC, we tried to find new LSD1 inhibitor using drug repurposing strategy from a compound library, and fenoldopam, an FDA-approved drug, was identified as a potent LSD1 inhibitor with IC50 = 0.8974 µM in a reversible manner. Molecular docking predicted that fenoldopam occupied the FAD cavity of LSD1, forming hydrogen bonds with surrounding residues. Moreover, fenoldopam inactivated LSD1 and performed antiproliferative activity against ACHN cells and promoted cells apoptosis in vitro. Taken together, fenoldopam was identified as a novel LSD1 inhibitor firstly, and may serve as a new skeleton for RCC therapy.

6.
Int Immunopharmacol ; 88: 106891, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32853927

RESUMO

BACKGROUND: The therapeutic approaches guided toward microRNAs (miRNAs) have been extensively explored in lupus nephritis (LN), but the precise position of miR-10a-3p posted in disease is not translated thoroughly. Therein, this work pivoting on miR-10a-3p was launched with the involvement of regenerating islet-derived 3 α (REG3A). METHODS: Peripheral blood samples from LN patients and healthy controls (n = 132) were collected. miR-10a-3p and REG3A expression in peripheral blood mononuclear cells were tested. Mice were injected with miR-10a-3p agomir, miR-10a-3p antagomir and/or REG3A low expression vector for presentation of their roles in renal function, T helper cell 17 (Th17)/regulatory cell (Treg) balance, renal pathological damage, JAK2/STAT3 pathway activation and renal injury in LN. The relation between miR-10a-3p and REG3A was tested. RESULTS: MiR-10a-3p was down-regulated while REG3A was up-regulated in LN. Restoring miR-10a-3p or silencing REG3A decreased Th17/Treg ratio in CD4+ T cells, inhibited JAK2/STAT3 pathway activation, ameliorated renal function, improved renal pathological damage and alleviated renal injury in LN. REG3A depletion negated the effects of down-regulated miR-10a-3p on LN. MiR-10a-3p targeted REG3A. CONCLUSION: The work elucidates that miR-10a-3p restoration decreases Th17/Treg ratio and attenuates renal injury in LN via inhibiting REG3A and the activation of JAK2/STAT3 pathway, which renews the therapeutic reference for LN management.

7.
Artif Organs ; 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32779737

RESUMO

Hypercytokines cause acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients, which is the main reason for intensive care unit treatment and the leading cause of death in COVID-19 patients. Cytokine storm is a critical factor in the development of ARDS. This study evaluated the efficacy and safety of Oxiris filter in the treatment of COVID-19 patients. Five patients with COVID-19 who received continuous renal replacement therapy (CRRT) in Henan provincial people's hospital between January 23, 2019 and March 28, 2020, were enrolled in this study. Heart rate (HR), mean arterial pressure (MAP), oxygenation index (PaO2 /FiO2 ), renal function, C-reactive protein (CRP), cytokines, procalcitonin (PCT), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure score (SOFA), and prognosis were compared after CRRT. Five COVID-19 patients, three males and two females, aged 70.2 ± 19.6 years, were enrolled. After treatment, HR (101.4 ± 14.08 vs. 83.8 ± 6.22 bpm/min), CRP (183 ± 25.21 vs. 93.78 ± 70.81 mg/L), IL-6 (3234.49 (713.51, 16038.36) vs. 181.29 (82.24, 521.39) pg/mL), IL-8 (154.86 (63.97, 1476.1) vs. 67.19 (27.84, 85.57) pg/mL), and IL-10 (17.43 (9.14, 41.22) vs. 4.97 (2.39, 8.70) pg/mL), APACHE II (29 ± 4.92 vs. 18.4 ± 2.07), and SOFA (17.2 ± 1.92 vs. 11.2 ± 3.4) significantly decreased (P < .05), while MAP (75.8 ± 4.92 vs. 85.8 ± 6.18 mm Hg), and PaO2 /FiO2 (101.2 ± 7.49 vs. 132.6 ± 26.15 mm Hg) significantly increased (P < .05). Among the five patients, negative conversion of nucleic acid test was found in three cases, while two cases died. No adverse events occurred during the treatment. Our study observed a reduced level of overexpressed cytokines, stabilization of hemodynamic status, and staged improvement of organ function during the treatment with Oxiris filter.

11.
JMIR Mhealth Uhealth ; 8(7): e19417, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32568722

RESUMO

BACKGROUND: The coronavirus disease (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in the self-quarantine of countless people due to possible infection. This situation makes telemedicine necessary as it can overcome geographical barriers, increase the number of people served, and provide online clinical support for patients. However, the outcomes of telemedicine have not yet been evaluated. OBJECTIVE: The aim of our study is to describe the epidemiological features and clinical symptoms of patients receiving remote diagnosis and treatment at the online outpatient clinic of our hospital, as well as to analyze the outcomes and advantages of telemedicine, during the COVID-19 pandemic. METHODS: Data from patients receiving remote diagnosis and treatment via consultation services for COVID-19 concerns at the online outpatient clinic of Henan Provincial People's Hospital from January 24 to February 17, 2020, were collected. A retrospective analysis was performed on epidemiological features, clinical symptoms, and preliminary outcomes. RESULTS: Online inquiry, consultation, and suggestions were provided for patient concerns related to COVID-19. Our hospital also offered offline noncontact drug delivery services following online ordering and payment. A total of 4589 patients receiving remote diagnosis and treatment were recruited. The daily number of online outpatient visits initially increased and then decreased, reaching its peak on January 28 when the daily number of online outpatient visits totaled 612. Of 4589 patients, 1940 (42.3%) were males and 2649 (57.7%) were females (age range: 78 days to 85 years). Most patients were aged 20-39 years (n=3714, 80.9%) and came from Henan Province (n=3898, 84.9%). The number of patients from other provinces was 691 (15.1%). During the online consultations, patients discussed the following symptoms: fever (n=2383), cough (n=1740), nasal obstruction (n=794), fatigue (n=503), and diarrhea (n=276). A total of 873 orders of noncontact drug delivery following online payment was completed. The daily number of such orders gradually stabilized after the initial, steady increase. For offline drug delivery orders, the median (IQR) was 36 (58). An online satisfaction survey was filled out postconsultation by patients; of the 985 responses received, 98.1% (n=966) of respondents were satisfied with the service they received. CONCLUSIONS: Remote diagnosis and treatment offered via online outpatient consultations effectively reduced the burden on hospitals, prevented overcrowding, reduced the risk of cross-infection, and relieved patients' anxiety during the COVID-19 outbreak. This plays an essential role in pandemic management.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Surtos de Doenças , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Telemedicina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
BMC Nephrol ; 21(1): 155, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349711

RESUMO

BACKGROUND: Whether ligation of the dorsal branch of the cephalic vein during the surgical establishment of the radiocephalic arteriovenous fistula (RCAVF) favorably or adversely affects the patency rate of the RCAVF remains controversial. We performed a randomized controlled trial to evaluate the effect of dorsal branch ligation on the patency rate of RCAVF. METHODS: A total of 115 patients who underwent surgical establishment were randomized to two groups treated with or without ligation of the dorsal branch of the cephalic vein during the surgical process. The primary patency rates of the RCAVF at 90, 270, and 360 days after the surgery and the secondary patency rates during a follow-up up to 1 year were compared. RESULTS: The patency rate did not differ significantly between the two groups at 3, 9, or 12 months after the procedure (P > 0.05). The combined primary patency rates of the RCAVF in patients from both groups at 3, 9 and 12 months after the procedure were 87.6, 82, and 74.5% respectively, while the combined secondary patency rate was 92.2% at the 1-year follow-up. The Log-rank test indicated that the initial patency rate and secondary patency rate did not differ significantly between the two groups (P = 0.674 and 0.759, respectively). CONCLUSION: This clinical study indicated that ligation of the dorsal branch of the cephalic vein does not significantly affect the patency of the arteriovenous fistula with a 1-year follow-up. TRIAL REGISTRATION: ISRCTN ISRCTN12288675, Registered 25 September 2019 in the ISRCTN registry. retrospectively registered.

14.
Front Med ; 14(3): 293-304, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31884526

RESUMO

Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

15.
Biochem Biophys Res Commun ; 519(1): 172-178, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31492499

RESUMO

Renal clear cell carcinoma (RCC) is the most common pathological type of renal carcinoma and drug resistance often occurs. We studied the effect of hsa_circ_0035483 on gemcitabine sensitivity in RCC, and explored its regulatory effect on downstream hsa-miR-335 and Cyclin B1 (CCNB1). High-throughput sequencing was used to analyze the differentially expressed circRNA in RCC. The expressions of hsa_circ_0035483, hsa-miR-335, CCNB1, and autophagy-related proteins were detected by RT-PCR or Western blot. The target relationships were revealed by RNA pulldown assay and dual luciferase report assay. Autophagy marker LC3 was detected by immunofluorescence. Cell viability was detected by MTT assay. Hsa_circ_0035483 can facilitate gemcitabine-induced autophagy, and enhance the resistance of RCC to gemcitabine. Hsa-miR-335 is the target regulatory point of hsa_circ_0035483. In addition, hsa_circ_0035483 promotes autophagy and tumor growth and enhances gemcitabine resistance in RCC by regulating hsa-miR-335/CCNB1, and silenced hsa_circ_0035483 can enhance gemcitabine sensitivity in vivo. Hsa_circ_0035483 may be the target of gemcitabine resistance in the treatment of RCC.


Assuntos
Autofagia/genética , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/metabolismo , RNA Circular/metabolismo , Animais , Autofagia/efeitos dos fármacos , Sequência de Bases , Linhagem Celular Tumoral , Ciclina B1/genética , Ciclina B1/metabolismo , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , RNA Circular/genética
16.
BMJ Open ; 9(9): e023162, 2019 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-31501092

RESUMO

INTRODUCTION: Starting dialysis early or late both result in a low quality of life and a poor prognosis in patients undergoing haemodialysis. However, there remains no consensus on the optimal timing of dialysis initiation, mainly because of a lack of suitable methods to assess variations in dialysis initiation time. We have established a novel equation named DIFE (Dialysis Initiation based on Fuzzy-mathematics Equation) through a retrospective, multicentre clinical cohort study in China to determine the most suitable timing of dialysis initiation. The predictors of the DIFE include nine biochemical markers and clinical variables that together influence dialysis initiation. To externally validate the clinical accuracy of DIFE, we designed the assessment of DIFE (ADIFE) study as a prospective, open-label, multicentre, randomised controlled trial to assess the clinical outcomes among patients who initiate dialysis in an optimal start dialysis group and a late-start dialysis group, based on DIFE. METHODS AND ANALYSIS: A total of 388 enrolled patients with end-stage renal disease will be randomised 1:1 to the optimal start dialysis group, with a DIFE value between 30 and 35, or the late-start dialysis group, with a DIFE value less than 30, using the Randomization and Trial Supply Management system. Participants will be assessed for changes in signs and symptoms, dialysis mode and parameters, biochemical and inflammatory markers, Subjective Global Assessment, Kidney Disease Quality of Life Short Form, Cognitive Assessment, medical costs, adverse events and concomitant medication at baseline, predialysis visiting stage and postdialysis visiting stage, every 12-24 weeks. The following data will be recorded on standardised online electronic case report forms. The primary endpoint is 3-year all-cause mortality. The secondary endpoints include non-fatal cerebrocardiovascular events, annual hospitalisation rate, quality of life, medical costs and haemodialysis related complications. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of the First Affiliated Hospital of Dalian Medical University China (registration no: YJ-KY-2017-119) and the ethics committees of all participating centres. The final results of the ADIFE trial will be presented to the study sponsor, clinical researchers and the patient and public involvement reference group. Findings will be disseminated through peer-reviewed journals, Clinical Practice Guidelines and at scientific meetings. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov. Registry (NCT03385902); pre-results.


Assuntos
Falência Renal Crônica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/normas , Tempo para o Tratamento/normas , Adulto , Algoritmos , Estudos de Coortes , Feminino , Lógica Fuzzy , Humanos , Masculino , Estudos Prospectivos , Projetos de Pesquisa
17.
Sci Rep ; 9(1): 5871, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971708

RESUMO

In order to develop an equation that integrates multiple clinical factors including signs and symptoms associated with uraemia to assess the initiation of dialysis, we conducted a retrospective cohort study including 25 haemodialysis centres in Mainland China. Patients with ESRD (n = 1281) who commenced haemodialysis from 2008 to 2011 were enrolled in the development cohort, whereas 504 patients who began haemodialysis between 2012 and 2013 were enrolled in the validation cohort comprised. An artificial neural network model was used to select variables, and a fuzzy neural network model was then constructed using factors affecting haemodialysis initiation as input variables and 3-year survival as the output variable. A logistic model was set up using the same variables. The equation's performance was compared with that of the logistic model and conventional eGFR-based assessment. The area under the bootstrap-corrected receiver-operating characteristic curve of the equation was 0.70, and that of two conventional eGFR-based assessments were 0.57 and 0.54. In conclusion, the new equation based on Fuzzy mathematics, covering laboratory and clinical variables, is more suitable for assessing the timing of dialysis initiation in a Chinese ESRD population than eGFR, and may be a helpful tool to quantitatively evaluate the initiation of haemodialysis.


Assuntos
Falência Renal Crônica/patologia , Redes Neurais de Computação , Adulto , Idoso , Área Sob a Curva , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Diálise Renal , Estudos Retrospectivos , Fatores de Tempo
18.
Medicine (Baltimore) ; 98(6): e14376, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732173

RESUMO

There are few studies on the correlation between red blood cell distribution width (RDW) and cardiovascular events in the patients receiving peritoneal dialysis (PD). We explored the correlation between RDW and cardiovascular events in PD patients and possible mechanism.A total of 138 PD patients were divided into RDW < 15% group (n = 104) and RDW ≥ 15% group (n = 34).The levels of serum C-reactive protein (CRP) [3.05 (0.79, 15.30) mg/L vs 2.15 (1.00, 6.50) mg/L] and parathyroid hormone (PTH) [260.0 (192.7, 352.6) ng/L vs 200.7 (118.0, 319.7) ng/L] were significantly higher, but the levels of serum albumin [30.65 (27.4,32.8) g/L vs 32.3 (29.25,34.95) g/L], prealbumin [(299 ±â€Š96) g/L vs (346 ±â€Š86) g/L], triglyceride [1.24 (0.72, 1.50) mmol/L vs 1.42 (1.12,1.84) mmol/L], and transferrin saturation [27.9 (16.4, 43.6)% vs 37.8 (23.3, 57.2)%] were significantly lower in the RDW ≥ 15% group than in the RDW < 15% group (all P < 0.05). The RDW was negatively correlated with albumin (r = - 0.258, P = 0.002), prealbumin (r = -0.236, P = 0.005), and triglyceride (r = -0.194, P = 0.023), but was positively correlated with CRP level (r = 0.174, P = 0.041). The incidence of cardiovascular events was significantly higher in the RDW ≥ 15% group (6 patients, 17.6%) than in the RDW < 15% group (6.7%) (7 patients, P < 0.01). Cox proportional hazard model showed that elevated RDW level was an independent risk factor for cardiovascular events in PD patients (HR = 1.622, 95% CI: 1.063-2.475, P = 0.025).The elevated RDW may be served as a risk factor to predict the cardiovascular events in PD patients.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Eritrócitos/metabolismo , Diálise Peritoneal/estatística & dados numéricos , Adulto , Proteína C-Reativa , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Pré-Albumina/análise , Albumina Sérica
19.
Ann Transl Med ; 7(23): 765, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32042781

RESUMO

Background: The characteristics of mesenchymal stem cells (MSCs) in the repair of acute kidney injury (AKI) have been extensively studied. However, some potential molecular mechanisms remain indistinct. The aim of this study was to combine published microRNA (miRNA) transcriptional profiling with quantitative proteomic analyses to reveal specific miRNAs or genes for MSC-based therapy in AKI. Methods: Transcriptome data containing significantly changed miRNAs in renal tissue from AKI mice treated with and without MSCs were downloaded. Proteomics resources were downloaded from a human proximal renal tubule cell line (HK-2) that served as a good in vitro model for AKI treated with MSCs. We connected the proteomics data with transcriptional records based on miRNA function. Differentially expressed genes (DEGs) were sorted. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted, and protein-protein interaction (PPI) chains were formed. The genes identified in the analyses were verified in a cisplatin-induced AKI rat model and in HK-2 cells exposed to cisplatin and cocultured with MSCs. Results: A total of 207 specific DEGs were sorted. The ribosomal pathway was identified in pathway enrichment, and ribosomal proteins were identified from the PPI network complex. The targeting of the microRNAs, miR-107 to RPS19, was directly verified by the dual-luciferase method. miR-107 knockdown induced RPS19 expression, protected HK-2 cells from cisplatin-induced apoptosis, and promoted cell proliferation. Conclusions: By analyzing comprehensive bioinformatics data, we have confirmed the DEGs and pathways in AKI treated with MSCs. Bone marrow-derived MSCs reduce miR-107 expression and increase RPS19 expression by repressing the proliferation of cisplatin-induced AKI cells and initiating apoptosis.

20.
Pharmacogenomics J ; 19(3): 277-285, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30237582

RESUMO

Xuesaitong (XST) is mainly used to treat cardiovascular and cerebrovascular diseases, sometimes causing cutaneous adverse drug reactions (cADRs) with unknown mechanisms of pathogenicity or risk factors. We aimed to verify whether human leukocyte antigen (HLA) alleles are associated with XST-related cADRs in Han Chinese population. We carried out an association study including 12 subjects with XST-induced cADRs, 283 controls, and 28 XST-tolerant subjects. Five out of 12 patients with XST-induced cADRs carried HLA-C*12:02, and all of them received XST via intravenous drip. The carrier frequency of HLA-C*12:02 was significantly high compare to that of the control population (Pc = 4.4 × 10-4, odds ratio (OR) = 21.75, 95% CI = 5.78-81.88). Compared with that of the XST-tolerant group, the patients who received XST through intravenous drip presented a higher OR of cADRs (Pc = 0.011, OR = 27.00, 95% CI = 2.58-282.98). The results suggest that HLA-C*12:02 is a potentially predictive marker of XST-induced cADRs in Han Chinese, especially when XST is administered via intravenous drip.


Assuntos
Erupção por Droga/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Medicamentos de Ervas Chinesas/efeitos adversos , Predisposição Genética para Doença/genética , Antígenos HLA-C/genética , Saponinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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