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1.
Theranostics ; 9(24): 7239-7250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695765

RESUMO

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is growing in incidence but treatment options remain limited, particularly for late stage disease. As liver cirrhosis is the principal risk state for HCC development, markers to detect early HCC within this patient population are urgently needed. Perturbation of epigenetic marks, such as DNA methylation (5mC), is a hallmark of human cancers, including HCC. Identification of regions with consistently altered 5mC levels in circulating cell free DNA (cfDNA) during progression from cirrhosis to HCC could therefore serve as markers for development of minimally-invasive screens of early HCC diagnosis and surveillance. Methods: To discover DNA methylation derived biomarkers of HCC in the background of liver cirrhosis, we profiled genome-wide 5mC landscapes in patient cfDNA using the Infinium HumanMethylation450k BeadChip Array. We further linked these findings to primary tissue data available from TCGA and other public sources. Using biological and statistical frameworks, we selected CpGs that robustly differentiated cirrhosis from HCC in primary tissue and cfDNA followed by validation in an additional independent cohort. Results: We identified CpGs that segregate patients with cirrhosis, from patients with HCC within a cirrhotic liver background, through genome-wide analysis of cfDNA 5mC landscapes. Lasso regression analysis pinpointed a panel of probes in our discovery cohort that were validated in two independent datasets. A panel of five CpGs (cg04645914, cg06215569, cg23663760, cg13781744, and cg07610777) yielded area under the receiver operating characteristic (AUROC) curves of 0.9525, 0.9714, and 0.9528 in cfDNA discovery and tissue validation cohorts 1 and 2, respectively. Validation of a 5-marker panel created from combining hypermethylated and hypomethylated CpGs in an independent cfDNA set by bisulfite pyrosequencing yielded an AUROC of 0.956, compared to the discovery AUROC of 0.996. Conclusion: Our finding that 5mC markers derived from primary tissue did not perform well in cfDNA, compared to those identified directly from cfDNA, reveals potential advantages of starting with cfDNA to discover high performing markers for liquid biopsy development.

2.
Nurs Health Sci ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31698541

RESUMO

Patient empowerment has been shown to have some positive impacts on self-efficacy, self-esteem, and recovery. However, information about the empowerment needs of patients after a percutaneous coronary intervention is scarce. The aim of this study was to develop a Chinese-language instrument to measure empowerment needs of such patients. The initial instrument was generated based on a literature review and interviews with patients after a percutaneous coronary intervention procedure. Content validity was tested with a panel of experts using the Delphi method. In total, 226 patients were recruited for psychometric tests using the revised instrument. Expert authority coefficient was 0.92, and content validity index was 0.95. The internal consistency reliability was demonstrated by Cronbach's α coefficients (0.86 for the total score, 0.66-0.74 for the dimensions). The newly developed 19-item, five-dimension instrument has shown satisfactory validity (face/content validity and construct validity) and internal consistency reliability. The instrument could help clinical nurses who have close contact with patients after a percutaneous coronary intervention to gain a better understanding of their empowerment needs and could help develop appropriate health education to address such needs.

3.
Int J Med Inform ; 133: 104010, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31675540

RESUMO

BACKGROUND: Given that China has free universities dedicated solely to the elderly, such universities may be the perfect place to provide large numbers of elderly with a systematic program of self-management. Yet, testing health applications in this location has not occurred, partly because time-consuming training is required before applications can be used. OBJECTIVE: This study aimed to develop and implement a smartphone training program for the elderly and to confirm the effects on smartphone competency and quality of life. METHODS: A randomized controlled trial was conducted. Participants were randomly assigned to either the intervention group or the wait-list control group. A smartphone operation manual was provided to all participants. The intervention group received the smartphone training program once a week for 20 weeks. After the study was finished, participants in the wait-list control group were permitted to undergo the smartphone training program. RESULTS: Of the 344 participants were randomized at the elder university in Huzhou. After 20 weeks of the intervention, the intervention group showed significant improvement in smartphone usage competency (except health applications) and quality of life relative to the wait-list control group (P < 0.05). CONCLUSION: This study confirmed the effectiveness of the smartphone training program in the elder university setting. However, further research is needed to strengthen the intervention in the area of health applications.

4.
BMC Geriatr ; 19(1): 313, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729965

RESUMO

BACKGROUND: Anxiety symptoms are pervasive among elderly populations around the world. The Geriatric Anxiety Inventory (the GAI) has been developed and widely used in screening those suffering from severe symptoms. Although debates about its dimensionality have been mostly resolved by Molde et al. (2019) with bifactor modeling, evidence regarding its measurement invariance across sex and somatic diseases is still missing. METHODS: This study attempted to provide complemental evidence to the dimensionality debates of the GAI with Mokken scale analysis and to examine its measurement invariance across sex and somatic diseases by conducting differential item functioning (DIF) analysis among a sample of older Chinese adults. The data was from responses of a large representative sample (N = 1314) in the Chinese National Survey Data Archive, focusing on the mental health of elderly adults. RESULTS: The results of Mokken scale analysis confirmed the unidimensionality of the GAI, and DIF analysis indicated measurement invariance of this inventory across individuals with different sex and somatic diseases, with just a few items exhibiting item bias but all of them negligible. CONCLUSIONS: All these findings supported the use of this inventory among Chinese elders to screen anxiety symptoms and to make comparisons across sex and somatic diseases.

5.
Virol J ; 16(1): 129, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699105

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever that was first described in China in 2011. We report a patient who died of Severe fever with thrombocytopenia syndrome virus (SFTSV) infection, with a rapidly progressive central nervous system (CNS) disturbance, in Dongyang, Zhejiang Province, China, in 2017. CASE PRESENTATION: A 64-year-old man was admitted to hospital after 4 days of fever. SFTSV was detected 1 day after the patient was admitted to hospital. The patient presented with CNS disturbance and died 4 days after admission. Detailed clinical and epidemiological investigations and laboratory tests were conducted. Reduced platelet, white blood cell, lymphocyte, and neutrophil counts, elevated lactate dehydrogenase, creatine kinase, aspartate aminotransferaseand alanine aminotransferase concentrations, and an increased activated partial thromboplastin time were observed. In a phylogenetic analysis, the isolate clustered close to a strain derived from South Korea. CONCLUSIONS: This is the first case of SFTSV infection with CNS disturbance in Dongyang, Zhejiang Province, China. The surveillance of suspected cases of SFTS is important in SFTSV endemic regions.

6.
Am J Hum Genet ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31679651

RESUMO

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples. We performed low-pass GS retrospectively for 1,090 RM-affected couples, all of whom had routine chromosome analysis. A customized sequencing and interpretation pipeline was developed to identify chromosomal rearrangements and deletions/duplications with confirmation by fluorescence in situ hybridization, chromosomal microarray analysis, and PCR studies. Low-pass GS yielded results in 1,077 of 1,090 couples (98.8%) and detected 127 chromosomal abnormalities in 11.7% (126/1,077) of couples; both members of one couple were identified with inversions. Of the 126 couples, 39.7% (50/126) had received former diagnostic results by karyotyping characteristic of normal human male or female karyotypes. Low-pass GS revealed additional chromosomal abnormalities in 50 (4.0%) couples, including eight with balanced translocations and 42 inversions. Follow-up studies of these couples showed a higher miscarriage/fetal-anomaly rate of 5/10 (50%) compared to 21/93 (22.6%) in couples with normal GS, resulting in a relative risk of 2.2 (95% confidence interval, 1.1 to 4.6). In these couples, this protocol significantly increased the diagnostic yield of chromosomal abnormalities per couple (11.7%) in comparison to chromosome analysis (8.0%, chi-square test p = 0.000751). In summary, low-pass GS identified underlying chromosomal aberrations in 1 in 9 RM-affected couples, enabling identification of a subgroup of couples with increased risk of subsequent miscarriage who would benefit from a personalized intervention.

7.
BMC Neurol ; 19(1): 272, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690277

RESUMO

BACKGROUD: Patients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear. METHODS: We retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed. RESULTS: FT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI) networks. Three modules were selected from PPI, of which MMP4, ADRA2C and EIF3E were recognized as the seed genes. CONCLUSIONS: Low FT3 value on admission was associated with stroke severity, subtype and prognosis. In addition, DEGs identified from bioinformatics analysis are likely to be candidates for elucidating clinical outcomes with low FT3, and provide us with therapeutic targets for improving stroke prognosis.

8.
J Cell Physiol ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654396

RESUMO

Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMP-activated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway.

9.
Cell Death Dis ; 10(10): 777, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611604

RESUMO

MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET expression were examined in EGFR-activating mutated NSCLC by immunohistochemical (IHC) analysis. The relationship between COX2, TOPK, and MET was explored in vitro and ex vivo. In addition, the inhibition of HCC827GR cell growth by combining COX2 inhibitor (celecoxib), TOPK inhibitor (pantoprazole), and gefitinib was verified ex vivo and in vivo. We found that COX2 and TOPK were highly expressed in EGFR-activating mutated NSCLC and the progression-free survival (PFS) of triple-positive (COX2, MET, and TOPK) patients was shorter than that of triple-negative patients. Then, we observed that the COX2-TXA2 signaling pathway modulated MET through AP-1, resulting in an inhibition of apoptosis in gefitinib-resistant cells. Moreover, we demonstrated that MET could phosphorylate TOPK at Tyr74 and then prevent apoptosis in gefitinib-resistant cells. In line with these findings, the combination of celecoxib, pantoprazole, and gefitinib could induce apoptosis in gefitinib-resistant cells and inhibit tumor growth ex vivo and in vivo. Our work reveals a novel COX2/MET/TOPK signaling axis that can prevent apoptosis in gefitinib-resistant cells and suggests that a triple combination of FDA-approved drugs would provide a low-cost and practical strategy to overcome gefitinib resistance.

10.
J Agric Food Chem ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31642668

RESUMO

Atherosclerosis, the major risk of cardiovascular events, is a chronic vascular inflammatory disease. Pterostilbene is a naturally occurring dimethylated analogue of resveratrol and has recently been demonstrated to be beneficial against cardiovascular diseases. However, the underlying mechanisms of pterostilbene on atherosclerosis remain elusive. Experimental atherosclerosis was induced by a high-fat diet (HFD) in apolipoprotein E knockout (ApoE-/-) mice. Pterostilbene was administered intragastrically for 16 weeks. We found that pterostilbene significantly attenuated thoracic and abdominal atherosclerotic plaque formation in HFD-fed ApoE-/-mice, accompanied by modulated lipid profiles and reduced production of proinflammatory cytokines (including IL-6, IFN-γ, and TNF-α). In addition, pterostilbene restored vascular redox balance in thoracic and abdominal aorta, evidenced by enhanced catalase (CAT) expression and activities, and decreased malondialdehyde and H2O2 production. Notably, pterostilbene specifically induced CAT expression and activities in the vascular smooth muscle cells (VSMCs) of thoracic and abdominal aorta. In vitro, pterostilbene markedly promoted the expression and activity of CAT and decreased ox-low-density lipoprotein (LDL)-mediated VSMC proliferation and intracellular H2O2 production, which was abolished by CAT siRNA knockdown or inhibition. Pterostilbene-induced CAT expression was associated with inhibition of Akt, PRAS40, and GSK-3ß signaling activation and upregulation of PTEN. Our data clearly demonstrated that pterostilbene exerted an antiatherosclerotic effect by inducing CAT and modulating the VSMC function.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31636065

RESUMO

GLS4 is a novel inhibitor of the hepatitis B virus (HBV) capsid assembly with inhibitory activities against nucleot(s)ide-resistant HBV strains. This study investigated the pharmacokinetics, safety, and tolerability of GLS4 and the effects of food and ritonavir in healthy adults. GLS4 was administered in a single-ascending-dose study over 1-240 mg and multiple-ascending-dose study that ranged from 30 mg once daily to 180 mg thrice daily. The drug interaction study included sequential-design (day 1 for 120 mg GLS4 alone, day 5 for 100 mg ritonavir alone followed by 9 days of both drugs) and a placebo-control (9 days of both 240 mg GLS4 and 100 mg ritonavir). The results showed that the steady-state trough concentration of multiple dosing of GLS4 alone was significantly lower than the 90% effective concentration (EC90) of 55.7 ng/ml, even with increasing dosing frequency and dosage. An initial dose of 100 mg ritonavir significantly boosted plasma concentration at 24 h of 120 mg GLS4 from 2.40 ng/ml to 49.8 ng/ml (geometric mean ratio of 20.7, 90% confidence interval 17.0-25.3), while a milder effect was observed on the area under the curve (AUC)0-24h with a 7.42-fold increase and on Cmax, with a 4.82-fold increase. The pharmacokinetics change in GLS4 persisted after 9 days of chronic dosing, with a trough concentration of 182 ng/ml. Both single and multiple doses of GLS4 up to 240 mg with or without ritonavir were well tolerated. These results support the investigation of a novel HBV treatment regimen containing GLS4 with 100 mg ritonavir added solely to enhance GLS4 concentrations in plasma.

12.
Medicine (Baltimore) ; 98(38): e17219, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567979

RESUMO

RATIONALE: Retained placenta accreta is an increasing obstetric problem in recent years, and pulmonary embolism (PE) during pregnancy and the postpartum period is a vital condition, but lack of standard therapy guidelines. This report describes a case of postpartum PE combined with retained placenta accreta. PATIENT CONCERNS: A 27-year-old woman presenting with fever and dyspnea after delivery was admitted to our hospital with retained placenta accreta. DIAGNOSES: The patient was diagnosed with the infection, postpartum PE, and residual placenta. INTERVENTIONS: The antibiotics and low molecular weight heparin were initially started to cure the infection and control PE. Mifepristone was then used to promote the necrosis of residual placenta while long-term use of warfarin was served as continuous anticoagulant therapy. Hysteroscopic resection of retained placenta was not performed until thrombi had been almost disappeared after more than 2 months of anticoagulation therapy. OUTCOMES: The patient's menstruation returned to normal within several weeks after hysteroscopic resection and she completely recovered from PE after 3 months of anticoagulant therapy. LESSONS: Treatment of retained placenta accreta can be postponed when encountering complicated cases, such as postpartum PE. PE in perinatal stage can be managed referring to nonmaternal PE.


Assuntos
Placenta Acreta/terapia , Placenta Retida/terapia , Período Pós-Parto , Embolia Pulmonar/terapia , Adulto , Feminino , Humanos , Placenta Acreta/diagnóstico , Placenta Retida/diagnóstico , Gravidez , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/etiologia , Tomografia Computadorizada por Raios X
13.
Zhongguo Gu Shang ; 32(9): 806-809, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31615175

RESUMO

OBJECTIVE: To analyze the clinical effect of Zhuang medicine tendon therapy combined with chiropractic manipulation in treating sacroiliac joint dislocation. METHODS: From January 2017 to May 2018, 60 patients with sacroiliac joint dislocation were divided into treatment group and control group according to the order of admission. There were 19 males and 11 females in the treatment group, aged from 23 to 52 (38.97±3.23) years old, with a course of 2 h to 5.1 months, with an average of (2.19±1.12) months. There were 14 males and 16 females in the control group, aged from 26 to 50 (39.07±3.30) years old, with a course of 3 h to 6 months, with an average of(2.41±1.05) months. The treatment group was treated with Zhuang medicine tendon therapy combined with chiropractic manipulation, while the control group was treated with conventional acupuncture and massage. Before treatment, the main clinical symptoms of the patients were lumbosacral pain, posterior superior iliac spine not at the same level and accompanied with dyskinesia. The pelvic separation test and the "4" test were positive. After treatment, the curative effect was evaluated according to the improved Macnab standard and the "score of treatment of lumbar diseases". RESULTS: Sixty patients were followed up for an average of 8 months. At the latest follow-up, the clinical effect of modified Macnab was better in the treatment group than in the control group(P<0.01). After treatment, the treatment group was better than the control group on lumbar function score (P<0.01). CONCLUSIONS: The treatment of sacroiliac joint dislocation by Zhuang medicine tendon therapy combined with chiropractic manipulation has good clinical effect and is worth further application and development.


Assuntos
Luxações Articulares , Manipulação Quiroprática , Adulto , Feminino , Fixação Interna de Fraturas , Humanos , Luxações Articulares/terapia , Masculino , Pessoa de Meia-Idade , Articulação Sacroilíaca , Tendões , Adulto Jovem
14.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31642468

RESUMO

Neuron-specific enolase (NSE), also known as gamma (γ) enolase or enolase-2 (Eno2), is a form of glycolytic enolase isozyme and is considered a multifunctional protein. NSE is mainly expressed in the cytoplasm of neurons and neuroendocrine cells, especially in those of the amine precursor uptake and decarboxylation (APUD) lineage such as pituitary, thyroid, pancreas, intestine and lung. In addition to its well-established glycolysis function in the cytoplasm, changes in cell localization and differential expression of NSE are also associated with several pathologies such as infection, inflammation, autoimmune diseases and cancer. This article mainly discusses the role and diagnostic potential of NSE in some lung diseases.

15.
Stem Cell Res Ther ; 10(1): 312, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655619

RESUMO

BACKGROUND: Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is one of the new therapeutic strategies for treating ischemic brain and heart tissues. However, the poor survival rate of transplanted BMSCs in ischemic tissue, due to high levels of reactive oxygen species (ROS), limits the therapeutic efficacy of this approach. Considering that BMSC survival may greatly enhance the effectiveness of transplantation therapy, development of effective therapeutics capable of mitigating oxidative stress-induced BMSC apoptosis is an important unmet clinical need. METHODS: BMSCs were isolated from the 4-week-old male Sprague Dawley rats by whole bone marrow adherent culturing, and the characteristics were verified by morphology, immunophenotype, adipogenic, and osteogenic differentiation potential. BMSCs were pretreated with artemisinin, and H2O2 was used to induce apoptosis. Cell viability was detected by MTT, FACS, LDH, and Hoechst 33342 staining assays. Mitochondrial membrane potential (ΔΨm) was measured by JC-1 assay. The apoptosis was analyzed by Annexin V-FITC/PI and Caspase 3 Activity Assay kits. ROS level was evaluated by using CellROX® Deep Red Reagent. SOD, CAT, and GPx enzymatic activities were assessed separately using Cu/Zn-SOD and Mn-SOD Assay Kit with WST-8, Catalase Assay Kit, and Total Glutathione Peroxidase Assay Kit. The effects of artemisinin on protein expression of BMSCs including p-Erk1/2, t-Erk1/2, p-c-Raf, p-p90rsk, p-CREB, BCL-2, Bax, p-Akt, t-Akt, ß-actin, and GAPDH were measured by western blotting. RESULTS: We characterized for the first time the protective effect of artemisinin, an anti-malaria drug, using oxidative stress-induced apoptosis in vitro, in rat BMSC cultures. We found that artemisinin, at clinically relevant concentrations, improved BMSC survival by reduction of ROS production, increase of antioxidant enzyme activities including SOD, CAT, and GPx, in correlation with decreased Caspase 3 activation, lactate dehydrogenase (LDH) release and apoptosis, all induced by H2O2. Artemisinin significantly increased extracellular-signal-regulated kinase 1/2 (Erk1/2) phosphorylation, in a concentration- and time-dependent manner. PD98059, the specific inhibitor of the Erk1/2 pathway, blocked Erk1/2 phosphorylation and artemisinin protection. Similarly, decreased expression of Erk1/2 by siRNA attenuated the protective effect of artemisinin. Additionally, when the upstream activator KRAS was knocked down by siRNA, the protective effect of artemisinin was also blocked. These data strongly indicated the involvement of the Erk1/2 pathway. Consistent with this hypothesis, artemisinin increased the phosphorylation of Erk1/2 upstream kinases proto-oncogene c-RAF serine/threonine-protein kinase (c-Raf) and of Erk1/2 downstream targets p90 ribosomal s6 kinase (p90rsk) and cAMP response element binding protein (CREB). In addition, we found that the expression of anti-apoptotic protein B cell lymphoma 2 protein (BcL-2) was also upregulated by artemisinin. CONCLUSION: These studies demonstrate the proof of concept of artemisinin therapeutic potential to improve survival in vitro of BMSCs exposed to ROS-induced apoptosis and suggest that artemisinin-mediated protection occurs via the activation of c-Raf-Erk1/2-p90rsk-CREB signaling pathway.

16.
Perit Dial Int ; 39(5): 465-471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31501292

RESUMO

Background:Depression has been recognized as a risk factor for cognitive impairment (CI) from cross-sectional datasets. This multicenter prospective study investigated the association between depression and cognitive decline in peritoneal dialysis (PD) patients.Methods:This multicenter prospective cohort study included 458 PD patients who were followed up for 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function, Trail-Making Tests A and B for executive function, subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skill, and language ability. Depression was assessed using Zung's Self-Rating Depression Scale.Results:During the 2-year follow-up, patients with moderate/severe depression at baseline showed a significant decline in global cognitive function (80.5 ± 15.2 vs 76.6 ± 15.5, p = 0.008), while patients without depression or with mild depression kept a stable global cognitive function. In the meantime, patients without depression showed significant improvements in immediate memory, visuospatial skill, and language ability. However, no significant improvement in these parameters was shown in depression groups. In multivariable linear regression analysis, depression at baseline was a significant predictor of worsening global cognitive function, whether depression was analyzed as a continuous variable (odds ratio [OR] = -0.14, 95% confidence interval [CI] -0.27, -0.01, p = 0.031) or a rank variable (OR = -1.88, 95% CI -3.30, -0.45, p = 0.010). Moreover, higher depression score or more severe depression degradation was significantly associated with decline of immediate memory, delayed memory, and language skill.Conclusion:Depression was a significant risk factor for worsening of CI in PD patients.

17.
Biochem Biophys Res Commun ; 519(1): 73-80, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31477270

RESUMO

Gastric cancer (GC) is one of the most malignant tumors with high incidence and mortality worldwide, and the multidrug resistance (MDR) often results in chemotherapy failure in GC. DJ-1 has been well indicated to be associated with drug resistance in multiple cancers. However, the role of DJ-1 in the MDR of gastric cancer cells and its possible mechanism remain to be elucidated. Therefore, the current study was investigated whether DJ-1 expression is differential in parental gastric cancer cell SGC7901 and vincristine (VCR)-induced gastric cancer MDR cell SGC7901/VCR, and whether DJ-1 plays a significant role in development of MDR in gastric cancer. The results showed that DJ-1 expression in SGC7901/VCR cells was significantly higher than its sensitive parental SGC7901 cells. Furthermore, DJ-1 overexpressed gastric cancer cell line SGC7901/LV-DJ-1 led to the increase of cell survival rate, the IC50 of chemotherapeutic drugs and number of cell clones as well as decrease of cell cycle G0/G1 phase ratio compared with its parental cells under the treatment of VCR, adriamycin (ADR), 5-Fluorouracil (5-FU) and cisplatin (DDP). However, the DJ-1 knockdown stable cell line SGC7901/VCR/shDJ-1 reversed the above mentioned series of MDR. Moreover, it was found that upregulation of DJ-1 protein expression promoted the pumping rate of GC cells to ADR and reduced the apoptotic index of GC cells treated with chemotherapeutic drugs by upregulating P-gp and Bcl-2. Similarly, knocking down DJ-1, P-gp or Bcl-2 displayed a converse effect. In conclusion, the current study demonstrated that DJ-1 overexpression confers the MDR phenotype to SGC7901 cells and this process is related to DJ-1 promoting active efflux of drugs and enhancing the anti-apoptotic ability of MDR GC cells by upregulating P-gp and Bcl-2.

18.
Int J Biol Sci ; 15(9): 2016-2028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523201

RESUMO

Dry age-related macular degeneration (AMD), a leading cause of blindness in aged population, is directly associated with oxidative stress induced damage of the retinal pigmented epithelial (RPE) cells. In the current study, we investigated the role of AMPK in the protective effect of artemisinin, an FDA approved anti-malarial Chinese herbal drug, on RPE cell line D407, against H2O2 induced oxidative stress. Our results showed that artemisinin promoted the survival of D407 cells from H2O2. Artemisinin reduced intracellular ROS generation and oxidative stress, decreased LDH release and the loss of mitochondrial membrane potential in D407 cells treated with H2O2. Western blotting showed that artemisinin concentration- and time-dependently stimulated the phosphorylation of AMP-activated protein kinase (AMPK) in D407 cells while AMPK inhibitor Compound C or knock-down of AMPK by si-RNA, inhibited the survival protective effect of artemisinin. More importantly, artemisinin produced a similar protective effect in primary cultured retinal pigment cells which was also blocked by inhibitors of AMPK. Taken together, these results suggested that artemisinin promotes survival of human retinal pigment cells against H2O2-induced cell death at least in part through enhancing the activation of AMPK. Therefore, artemisinin may be a beneficial therapeutic candidate for the treatment of age-related diseases, including retinal disorders like AMD.

19.
J Adv Nurs ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31531988

RESUMO

AIMS: Depressive symptoms are common among kidney transplantation recipients. Previous studies have reported that fatigue and rumination are risk factors for depressive symptoms. To date, the underlying mechanisms of fatigue, rumination, and depressive symptoms among kidney transplantation recipients remain unclear. This study aimed to assess the prevalence of depressive symptoms and investigate whether rumination mediates the association between fatigue and depressive symptoms among kidney transplantation recipients. DESIGN: Cross-sectional study. METHODS: The study of 207 kidney transplantation recipients with an average age of 44.5 years was conducted from January 2017-July 2017. Sociodemographic and clinical characteristics, fatigue, rumination, and depressive symptoms data were collected. For the descriptive analysis, Pearson correlations and mediation analysis based on the PROCESS macro were used. RESULTS: The prevalence of depressive symptoms among kidney transplantation recipients was 21.7%. Rumination mediated the association between fatigue and depressive symptoms and the indirect effect was 0.19 (95% confidence interval: 0.10-0.28). CONCLUSION: Depressive symptoms were highly prevalent among kidney transplantation recipients. Rumination exerts a mediating role between fatigue and depressive symptoms. IMPACT: This study alerts physicians and nurses for the importance of considering the mental health of these patients and contributes to the development of effective depression management interventions.

20.
Inorg Chem ; 58(19): 12669-12677, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31498616

RESUMO

This work presents a density functional theory (DFT)-based theoretical study on the cross-coupling reaction of alkyl carboxylic acids and nitrogen nucleophiles via dual copper and photoredox catalysis developed by MacMillan et al. [Nature, 2018, 559, 83-87]. The calculations showed the mechanistic details of three subprocesses proposed in the experimental study, including production of alkyl radicals, iridium(III) photoredox cycle, and copper(I) thermalredox cycle. It is found that alkyl radicals can be easily produced from primary, secondary, or tertiary carboxylic acids through iodonium activation. The energetically most favorable cross-coupling pathway involves coordination, deprotonation, single electron transfer (SET), radical addition, and reductive elimination. For the chlorinated indazole nucleophile (R1), the preferred C-N coupling product from the 1H-tautomer is attributed to its higher stability relative to the 2H-tautomer and the high barrier involved in the tautomerism from the 1H-tautomer to the 2H-tautomer. Meanwhile, in the case of heterocycle (R2), the C-N cross-coupling preferentially occurs at the indazole nitrogen rather than at the primary amide nitrogen, which is confirmed to be due to the stronger acidity of the indazole N-H unit, in comparison with the primary amide N-H unit in the indazole side chain. The theoretical results provide help for understanding the molecular mechanism and regioselectivity of the title reaction.

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