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Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.
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Condrócitos , Células Matadoras Naturais , Osteoartrite , Humanos , Osteoartrite/imunologia , Células Matadoras Naturais/imunologia , Animais , Condrócitos/imunologia , Osteoclastos/imunologia , Sinoviócitos/imunologia , Sinoviócitos/metabolismo , Comunicação Celular/imunologia , Macrófagos/imunologiaRESUMO
BACKGROUND: Immune check-point inhibitors-induced colitis (ICPIs-induced colitis) is one of the immune-related side effects. Steroids and Infliximab are commonly used to treat it. The patients of our report were treated by Vedolizumab. CASE SUMMARY: The two patients went to the doctor with bloody stools and were treated by Sintilimab and Camrelizumab, respectively, for their malignant tumors. They were diagnosed as ICPIs-induced colitis based on endoscopic and histologic examination. The original immunotherapy was ceased while the anti-inflammatory therapy was introduced. The patients' colitis symptoms disappeared after the treatment and no recurrence was found during the follow-up period. The unique feature about the case reports is that Vedolizumab combined with short-term corticosteroids had achieved good therapeutic effects. CONCLUSION: For the symptoms of bloody diarrhea after the ICPIs treatment of cancer, the possibility of ICPIs-induced colitis should be considered. Vedolizumab combined with short-term corticosteroids may be appropriate for the treatment.
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Recently, biological drugs have played a leading role in the treatment of inflammatory bowel disease, and therapeutic drug monitoring (TDM) may be useful in maximizing their effectiveness. TDM involves the measurement of serum drug and anti-drug antibodies concentrations as the basis for dosage adjustments or drug conversions to achieve a higher response rate. We believe that concentration thresholds should be individualized based on patients' disease severity, extent and phenotype, and therapeutic purposes should also be considered, with higher cut-offs mainly needed for endoscopic and fistula healing than for symptomatic remission. Proactive and reactive TDM can help optimize treatment, especially in patients receiving anti-tumour necrosis factor, and guide dose adjustment or drug conversion with lower cost. TDM is a promising approach to achieve precision medicine and targeted medicine in the future.
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Produtos Biológicos , Doenças Inflamatórias Intestinais , Produtos Biológicos/uso terapêutico , Monitoramento de Medicamentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfaRESUMO
At present, treatments for Alzheimer's disease can temporarily relieve symptoms but cannot prevent the decline of cognitive ability and other neurodegenerative changes. Dendrobium nobile Lindl alkaloid is the main active component of Dendrobium nobile Lindl. Dendrobium nobile Lindl alkaloid has been shown to resist aging, prolong life span, and exhibit immunomodulatory effects in animals. This review summarizes the mechanisms behind the neuroprotective effects reported in Alzheimer's disease animal models. The neuroprotective effects of Dendrobium nobile Lindl alkaloid have not been studied in patients. The mechanisms by which Dendrobium nobile Lindl alkaloid has been reported to improve cognitive dysfunction in Alzheimer's disease animal models may be associated with extracellular amyloid plaque production, regulation of tau protein hyperphosphorylation, inhibition of neuroinflammation and neuronal apoptosis, activation of autophagy, and enhanced synaptic connections.
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Dyskinesia is a serious complication of Parkinson's disease during levodopa (L-DOPA) treatment. The pathophysiology of L-DOPA-induced dyskinesia (LID) is complex and not fully illuminated. At present, treatment of dyskinesia is quite limited. Recent studies demonstrated neuroinflammation plays an important role in development of LID. Thus, inhibition of neuroinflammation might open a new avenue for LID treatment. Resveratrol (RES) is the most well-known polyphenolic stilbenoid and verified to possess a large variety of biological activities. DA neurotoxicity was assessed via behavior test and DA neuronal quantification. The movement disorders of dyskinesia were detected by the abnormal involuntary movements scores analysis. Effects of RES on glial cells-elicited neuroinflammation were also explored. Data showed that RES attenuated dyskinesia induced by L-DOPA without affecting L-DOPA's anti-parkinsonian effects. Furthermore, RES generated neuroprotection against long term treatment of L-DOPA-induced DA neuronal damage. Meanwhile, RES reduced protein expression of dyskinesia molecular markers, ΔFOS B and ERK, in the striatum. Also, there was a strong negative correlation between DA system damage and ΔFOS B level in the striatum. In addition, RES inhibited microglia and astroglia activation in substantia nigra and subsequent inflammatory responses in the striatum during L-DOPA treatment. RES alleviates dyskinesia induced by L-DOPA and these beneficial effects are closely associated with protection against DA neuronal damage and inhibition of glial cells-mediated neuroinflammatory reactions.
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Discinesias/etiologia , Discinesias/fisiopatologia , Levodopa/efeitos adversos , Resveratrol/farmacologia , Animais , Biomarcadores , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Discinesias/tratamento farmacológico , Discinesias/metabolismo , Masculino , Oxidopamina/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Doença de Parkinson/fisiopatologia , Ratos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/fisiopatologiaRESUMO
Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Trato Gastrointestinal Superior , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Duodeno , Humanos , Estômago , Trato Gastrointestinal Superior/diagnóstico por imagemRESUMO
Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. Oxidative stress is one of key contributors to PD. Nuclear factor erythroid-2-related factor 2 (Nrf2) is considered to be a master regulator of many genes involved in anti-oxidant stress to attenuate cell death. Therefore, activation of Nrf2 signalling provides an effective avenue to treat PD. Ellagic acid (EA), a natural polyphenolic contained in fruits and nuts, possesses amounts of pharmacological activities, such as anti-oxidant stress and anti-inflammation. Recent studies have confirmed EA could be used as a neuroprotective agent in neurodegenerative diseases. Here, mice subcutaneous injection of rotenone (ROT)-induced DA neuronal damage was performed to investigate EA-mediated neuroprotection. In addition, adult Nrf2 knockout mice and different cell cultures including MN9D-enciched, MN9D-BV-2 and MN9D-C6 cell co-cultures were applied to explore the underlying mechanisms. Results demonstrated EA conferred neuroprotection against ROT-induced DA neurotoxicity. Activation of Nrf2 signalling was involved in EA-mediated DA neuroprotection, as evidenced by the following observations. First, EA activated Nrf2 signalling in ROT-induced DA neuronal damage. Second, EA generated neuroprotection with the presence of astroglia and silence of Nrf2 in astroglia abolished EA-mediated neuroprotection. Third, EA failed to produce DA neuroprotection in Nrf2 knockout mice. In conclusion, this study identified EA protected against DA neuronal loss via an Nrf2-dependent manner.
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Antioxidantes/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Ácido Elágico/farmacologia , Fator 2 Relacionado a NF-E2/fisiologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Rotenona/toxicidade , Animais , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Estresse OxidativoRESUMO
AIM: To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS: A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type). RESULTS: There were significant differences in age and gender distribution between DILI patients and PBC patients. Biochemical indexes (except ALB), immunological indexes, positive rates of autoantibodies (except SMA), and number of cases of patients with different ANA titers (except the group at a titer of 1:10000) significantly differed between DILI patients and PBC patients. Biochemical indexes, immunological indexes, and positive rate of autoantibodies were not quite similar in different types of DILI. PBC was histologically characterized mainly by edematous degeneration of hepatocytes (n = 30), inflammatory cell infiltration around bile ducts (n = 29), and atypical hyperplasia of small bile ducts (n = 28). DILI manifested mainly as fatty degeneration of hepatocytes (n = 15) and spotty necrosis or loss of hepatocytes (n = 14). CONCLUSION: Although DILI and PBC share some similar laboratory tests (biochemical and immunological indexes) and pathological findings, they also show some distinct characteristics, which are helpful to the differential diagnosis of the two diseases.
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Anticorpos Antinucleares/imunologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Cirrose Hepática Biliar/diagnóstico , Fígado/patologia , Adulto , Fatores Etários , Idoso , Ductos Biliares/patologia , Biópsia , China , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina A/imunologia , Cirrose Hepática Biliar/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores SexuaisRESUMO
OBJECTIVE: We applied a meta-analysis to explore the effect of ulinastatin (UTI) on the serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in Asian patients with acute pancreatitis (AP). METHODS: Various databases were searched based on stringent inclusion and exclusion criteria to extract relevant cohort studies. Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA) was applied for statistical analyses. RESULTS: A total of 113 relevant studies (67 in Chinese, 46 in English) were initially retrieved. Finally, 11 eligible studies were enrolled in our meta-analysis with 399 pancreatitis patients. Meta-analysis results showed that after being treated with UTI, the serum levels of CRP, IL-6, and TNF-α were evidently decreased (CRP: SMD = -2.697, 95% CI = -4.399 ~ -0.994, p = 0.002; IL-6: SMD = -5.268, 95% CI = -9.850 ~ -0.687, p = 0.024; TNF-α: SMD = -5.666, 95% CI = -11.083 ~ -0.249, p = 0.040). CONCLUSION: UTI can effectively reduce the serum levels of CRP, IL-6, and TNF-α in Asian patients with AP, suggesting that UTI has anti-inflammatory effect on Asian patients with AP.â©.
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Anti-Inflamatórios/uso terapêutico , Glicoproteínas/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediadores da Inflamação/sangue , Pancreatite/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Povo Asiático , Citocinas/sangue , Glicoproteínas/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversosRESUMO
Mesenchymal stem cells (MSCs) were reported to accelerate the curing of ulcerative colitis (UC). Altered expression of microRNAs (miRNAs) has recently revealed association with UC. However, the effect of adipose-derived MSCs (ASCs) on UC and the mechanism of how miRNAs regulate UC remain unclear. We investigated the effect of ASCs on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced UC in rat colon tissues. qRT-PCR and immunofluorescence analyses were performed to monitor the expression of miR-1236 and its target molecule, retinoid-related orphan receptor γ (RORγ). Regulation of the expression of RORγ by miR-1236 was assessed using luciferase reporter construct assays and miR-1236 mimic transfection. The relationship between miR-1236 and RORγ was further investigated in HT29 cells induced by TNF-α. ASCs highly ameliorated UC and decreased the inflammation markers in rats with TNBS-induced UC. In addition, ASCs upregulated the expression of miR-1236 and decreased the expression of RORγ in the TNBS-induced rat model of UC. The luciferase reporter assay and bioinformatic analysis demonstrated that the expression of RORγ was directly targeted and regulated by miR-1236. Specifically, the expression of RORγ was suppressed by miR-1236 mimic and enhanced by miR-1236 inhibitor. Furthermore, we demonstrated that exogenous miR-1236 mimic could inhibit the expression of RORγ in HT29 cell induced by TNF-α. ASCs effectively alleviated UC in rats with the expression of miR-1236 alteration, and miR-1236 may play important roles in UC by downregulating the expression of RORγ.
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Colite Ulcerativa/terapia , Transplante de Células-Tronco Mesenquimais/métodos , MicroRNAs/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Regiões 3' não Traduzidas , Tecido Adiposo/citologia , Animais , Células Cultivadas , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Injeções Intravenosas , Masculino , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ratos Wistar , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis (UC). METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on July 31, 2013. Inclusion criteria were: (1) Randomized controlled trial (RCT); (2) Patients treated for UC; and (3) Intervention was vedolizumab. The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, patient demographic information, response rate, remission rate, and adverse events. The primary outcome was clinical response rate, and the secondary outcomes were clinical remission rate and serious adverse events. Odds ratio (OR) with 95%CI were calculated for each outcome. RESULTS: Of 224 studies initially identified, three RCTs examining the use of vedolizumab meeting the inclusion criteria were included in the meta-analysis. All studies examined the use of vedolizumab at dosages ranging from 0.5 to 10 mg/kg body weight (one study used a standard dose of 300 mg). The follow-up periods were approximately 6 wk. The total number of patients in the intervention groups was 901, and in the control groups was 221. The mean age of the patients was approximately 41 years, and approximately half were males. The follow-up periods ranged from 43 d to 6 wk. The clinical response and remission rates were significantly higher for patients who received vedolizumab as compared to control patients (clinical response: OR = 2.69; 95%CI: 1.94-3.74, P < 0.001 and remission rate: OR = 2.72; 95%CI: 1.76-4.19, P < 0.001). Serious adverse events were not higher in patients that received vedolizumab. CONCLUSION: This analysis supports the use of vedolizumab for the treatment of UC.
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Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/diagnóstico , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Masculino , Razão de Chances , Indução de Remissão , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Aberrant expression of high mobility group box-1 protein (HMGB1) contributes to the progression of various inflammatory diseases. This meta-analysis focused on the clinical significance of serum HMGB1 levels in pancreatitis patients, with the goal of building a novel diagnostic score model. METHOD: We conducted a meta-analysis by searching in the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases without any language restrictions. Studies were pooled and standard mean difference (SMD) and its corresponding 95% confidence intervals (95% CIs) were calculated. Version 12.0 STATA software was used for statistical analysis. RESULTS: We performed a final analysis of 841 subjects from 12 clinical case-control studies. The meta-analysis results showed a positive association between serum HMGB1 levels and the progression of pancreatitis. In the subgroup analysis by country, high serum level of HMGB1 may be related to pancreatitis progression in China, Korea, Hungary, and Japan populations (all P < 0.05). CONCLUSION: The present meta-analysis indicated that serum HMGB1 level was statistically elevated in patients with pancreatitis, and thus serum levels of HMGB1 could be determined to be a useful biomarker for pancreatitis patients.
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Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/etiologia , Proteína HMGB1/sangue , Pancreatite/sangue , Pancreatite/etiologia , Biomarcadores , Estudos de Casos e Controles , HumanosRESUMO
This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).
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AIM: To investigate whether dairy product consumption is a risk factor for gastric cancer. METHODS: We searched the PubMed and Web of Science databases for English-language studies on dairy product consumption and gastric cancer risk that were published between October 1980 and September 2013. One author independently extracted data and assessed study quality. Based on the heterogeneity results, we used either the fixed effects model or the random effects model to compute the summary relative risks and 95% confidence intervals (CIs). We also analyzed subgroups according to the study design, geographic region, sex, and whether there were adjustments for confounders (smoking and drinking) with respect to the sources of heterogeneity. RESULTS: We found 39 studies that were potentially eligible for inclusion in this meta-analysis, including 10 cohort studies and 29 case-control studies. The summary relative risk for gastric cancer, comparing the highest and lowest dairy product consumption categories, was 1.06 (95%CI: 0.95-1.18). Specific analyses for milk, butter, and margarine yielded similar results, but the results for cheese and yogurt were different. There was significant heterogeneity for all studies (Q = 112.61; P = 0.000; I (2) = 67.1%). No publication bias was observed (Egger's test: P = 0.135; Begg's test: P = 0.365). There was a nonsignificant association between dairy product consumption and gastric cancer risk in the subgroup analysis for the study design, sex, geographic region, and whether there were adjustments for confounders (smoking and drinking). CONCLUSION: In our meta-analysis, dairy product consumption was associated with a nonsignificantly increased risk of gastric cancer. However, this result should be verified using large, well-designed prospective studies.
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Laticínios/efeitos adversos , Dieta/efeitos adversos , Neoplasias Gástricas/epidemiologia , Comportamento Alimentar , Humanos , Estilo de Vida , Razão de Chances , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/diagnósticoRESUMO
In this study we aimed to screen effective biomarkers for differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). By using the gene expression profile dataset GSE24287 including 47 ileal CD, 27 UC and 25 non-inflammatory bowel diseases control downloaded from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between UC patients and controls as well as between CD patients and controls (|log2FC(fold change)| > 1 and p < 0.05). Then Gene Ontology (GO) functional enrichment analyses were performed for these DEGs in two groups, followed by the construction of weight PPI (protein-protein interaction) networks. Subnets enriched for the PPIs and differentially expressed genes were constructed based on the weight PPI networks. The overlapping genes between the genes in the top 10 subnets with smallest p value and the DEGs were selected as the candidate genes of disease. A total of 75 DEGs were identified in UC group and 87 ones in CD group. There were 69 and 57 specific DEGs in CD group and UC group, respectively. The DEGs in CD group were mainly enriched in "inflammatory response" and "defense response", while the most significantly enriched GO terms in UC group were "anion transport" and "chemotaxis". FOS and SOCS3 were identified as candidate genes for CD and other three genes HELB, ZBTB16 and FAM107A were candidate genes for UC. In conclusion, there were distinct genetic alterations between UC and CD. The candidate genes identified in current study may be used as biomarkers for differential diagnosis of CD and UC.
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Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Perfilação da Expressão Gênica , Biologia Computacional/métodos , Diagnóstico Diferencial , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genômica/métodos , Humanos , Anotação de Sequência Molecular , Mapeamento de Interação de Proteínas , Mapas de Interação de ProteínasRESUMO
To identify key microRNAs (miRNAs) associated with hepatocellular carcinoma (HCC) using small RNA-seq data. Small RNA-seq data for two HCC samples and two normal samples were downloaded from NCBI Gene Expression Omnibus. MiRNAs were identified through database search. Differentially expressed miRNAs were screened out with t test and their target genes were retrieved. Functional enrichment analysis was performed to uncover their biological functions. Regulatory networks and core metabolic networks were also constructed to present the global patterns. In addition, new miRNAs and their target genes were predicted. A total of 59 differentially expressed miRNAs were obtained, 12 up-regulated and 47 down-regulated. A total of 3,306 target genes were retrieved for eight miRNAs. Pathway enrichment analysis for the target genes showed that "pathways in cancer" and "MAPK signaling pathway" were significantly over-represented. Functional enrichment analysis found that "biological regulation" and "macromolecule modification" were significantly related to the target genes. Two regulatory networks were constructed for up- and down-regulated differentially expressed miRNAs with information from Ingenuity Pathway Analysis database. Two metabolic networks were also established based upon "pathways in cancer" and "MAPK signaling pathway", consisting of miRNAs, target genes, compounds and others genes. Moreover, a number of new miRNAs and relevant target genes were predicted. Our study discloses a number of miRNAs as well as genes which may be involved in the development of HCC and these findings are beneficial in guiding future researches.
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Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Biologia Computacional , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Ligação ProteicaRESUMO
AIM: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death worldwide. This study aims to explore the molecular mechanism of PDAC and identify biologically active small molecules capable of targeting the sub-pathways which were dysregulated in the development of PDAC. METHODS: The gene expression profile of GSE28735 microarray data (including 45 matching pairs of pancreatic tumor and adjacent non-tumor tissues) was downloaded from GEO (Gene Expression Omnibus) database. Differentially expressed genes (DEGs) between pancreatic tumor tissues and non-tumor tissues were identified, and then the sub-pathway enrichment analysis was performed. Moreover, an approach based on targeting sub-pathways was used to reveal potential agents for PDAC. RESULTS: A total of 5315 DEGs were identified between pancreatic tumor tissues and non-tumor tissues with a false discovery rate of 0.01. Genes of collagen family and integrin receptor family which were involved in pathways of focal adhesion and ECM-receptor interaction respectively were differentially expressed in the pancreatic tumor tissue. Besides, a total of 85 small molecules including fludrocortisone, latamoxef and metronidazole were revealed by bioinformatics analysis. CONCLUSION: This study proposed the use of an approach based on targeting sub-pathways to identify potential agents for PDAC. The sub-pathways and small molecules discovered in this study were not only related to PDAC but also play a role in perturbing the development of PDAC.
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Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Antineoplásicos/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Colágeno/genética , Colágeno/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Integrinas/genética , Integrinas/metabolismo , Redes e Vias Metabólicas , Terapia de Alvo Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , TranscriptomaRESUMO
OBJECTIVES: Here, we reported our experience over 28 years with 133 cases of patients with Wilson's disease (WD) in order to illustrate the diverse clinical presentation and to improve understanding and early diagnosis of WD. METHODS: We reviewed the medical records of patients with WD at Shengjing Hospital of China Medical University from 1993 to 2011. The clinical manifestations and laboratory findings were analyzed. The diagnosis was based on the presence of Kayser-Fleisher (K-F) rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after penicillamine challenge. RESULTS: Among them, 93 patients mainly presented with hepatic manifestations, 27 with neural abnormalities, and 13 presented with others. Age range at diagnosis was wide (3-74 years, average 13·2 years), and five patients were over 40 years. The oldest one was aged 74 years and presented with neuropsychiatric disorder. The positive rate of K-F rings was 93·0%. The serum ceruloplasmin decreased in 83·6% patients, 24-hour urinary copper increased in 88·1% patients, and serum copper decreased in 68·9% patients. About 79·7% of patients were diagnosed within 6 months, but only 33·1% were diagnosed at their initial medical consultation. There was a substantial delay of up to 15 years. CONCLUSIONS: The clinical manifestation of WD is very diverse and no one feature is completely reliable. Doctors in many fields have opportunities to encounter this disease, and the most important thing is to be aware of the possibility of WD.
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Degeneração Hepatolenticular/diagnóstico , Adolescente , Adulto , Idoso , Ceruloplasmina/metabolismo , Criança , Pré-Escolar , Cobre/sangue , Cobre/urina , Diagnóstico Diferencial , Feminino , Degeneração Hepatolenticular/metabolismo , Degeneração Hepatolenticular/patologia , Humanos , Fígado/patologia , Hepatopatias/complicações , Hepatopatias/diagnóstico , Hepatopatias/patologia , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/patologia , Adulto JovemRESUMO
Irritable bowel syndrome (IBS) is common gastrointestinal problems. It is characterized by abdominal pain or discomfort, and is associated with changes in stool frequency and/or consistency. The etiopathogenesis of IBS may be multifactorial, as is the pathophysiology, which is attributed to alterations in gastrointestinal motility, visceral hypersensitivity, intestinal microbiota, gut epithelium and immune function, dysfunction of the brain-gut axis or certain psychosocial factors. Current therapeutic strategies are often unsatisfactory. There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS. Probiotics are living organisms which, when ingested in certain numbers, exert health benefits beyond inherent basic nutrition. Probiotics have numerous positive effects in the gastrointestinal tract. Recently, many studies have suggested that probiotics are effective in the treatment of IBS. The mechanisms of probiotics in IBS are very complex. The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.