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OBJECTIVE: This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN). METHODS: A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I2 was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols. RESULTS: The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile. CONCLUSIONS: Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
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Nefritis Lúpica , Humanos , Nefritis Lúpica/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Quimioterapia de Inducción , Metaanálisis en Red , Resultado del Tratamiento , Inmunosupresores/efectos adversos , Tacrolimus/efectos adversos , Ácido Micofenólico/efectos adversos , Inducción de Remisión , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The exceptional biocompatibility of emulsion systems that rely on stabilizing protein-polysaccharide particles presents extensive possibilities for the transportation of bioactive carriers, making them highly promising for various biological applications. The current work aimed to explore the phenomenon of complex coacervation between sesame protein isolate (SPI) and four distinct polysaccharides, namely, Arabic gum (GA), carrageenan (CAR), sodium carboxymethyl cellulose (CMC), and sodium alginate (SA). The study objective was achieved by fabricating emulsions through the blending of these polymers with oil at their maximum turbidity level (φ = 0.6), followed by the measurement of their rheological properties. The turbidity, ζ-potential, and particle size were among the techno-parameters analyzed to assess the emulsion stability. The microstructural characterization of the emulsions was conducted using both transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Furthermore, the functional properties were examined using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The SPI incorporated with SA, CMC, and CAR reached the maximum turbidity (0.2% w/v) at a ratio of 4:1, corresponding to the pH values of 4.5, 3, or 3.5, respectively. The SPI-GA mixture exhibited the maximum turbidity at a ratio of 10:1 and pH 4.5. Results from the FTIR and XRD analyses provided evidence of complex formation between SPI and the four polysaccharides, with the electrostatic and hydrogen bond interactions facilitating the binding of SPI to these polysaccharides. SPI was bound to the four polysaccharides through electrostatic and hydrogen bond interactions. The SPI-CMC and SPI-SA emulsions were more stable after two weeks of storage.
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DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution sequencing methodology that sequences complete genetics and the two most common cytosine modifications in a single workflow. DNA is copied and bases are enzymatically converted. Coupled decoding of bases across the original and copy strand provides a phased digital readout. Methods are demonstrated on human genomic DNA and cell-free DNA from a blood sample of a patient with cancer. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. Simultaneous, phased reading of genetic and epigenetic bases provides a more complete picture of the information stored in genomes and has applications throughout biomedicine.
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Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseasesâassociated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.
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Enfermedades Autoinmunes , Urticaria Crónica , Urticaria , Humanos , Estudio de Asociación del Genoma Completo , Urticaria/genética , Enfermedad Crónica , Urticaria Crónica/genética , Enfermedades Autoinmunes/genética , Inmunoglobulina G , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Receptores InmunológicosRESUMEN
Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study of over two thousand individual blood samples, we created, tested and explored the properties of a 5-hydroxymethylcytosine-based classifier to detect colorectal cancer (CRC). In an independent validation sample set, the classifier discriminated CRC samples from controls with an area under the receiver operating characteristic curve (AUC) of 90% (95% CI [87, 93]). Sensitivity was 55% at 95% specificity. Performance was similar for early stage 1 (AUC 89%; 95% CI [83, 94]) and late stage 4 CRC (AUC 94%; 95% CI [89, 98]). The classifier could detect CRC even when the proportion of tumor DNA in blood was undetectable by other methods. Expanding the classifier to include information about cell-free DNA fragment size and abundance across the genome led to gains in sensitivity (63% at 95% specificity), with similar overall performance (AUC 91%; 95% CI [89, 94]). We confirm that 5-hydroxymethylcytosine can be used to detect CRC, even in early-stage disease. Therefore, the inclusion of 5-hydroxymethylcytosine in multianalyte testing could improve sensitivity for the detection of early-stage cancer.
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Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , ADN/genética , Detección Precoz del Cáncer/métodos , Humanos , Sensibilidad y EspecificidadRESUMEN
Cutaneous T-cell lymphomas (CTCLs) are a kind of non-Hodgkin lymphoma that originates from skin, which is difficult to treat with traditional drugs. Human histone deacetylase inhibitors (HDACi) targeted therapy has become a promising treatment strategy in recent years, but some patients can develop resistance to the drug, leading to treatment failure. There are no public reports on whether alternative splicing (AS) and RNA binding proteins (RBP) affect the efficacy of targeted therapy. Using data from the Gene Expression Omnibus (GEO) database, we established a co-change network of AS events and RBP in CTCLs for the first time, and analyzed the potential regulatory effects of RBP on HDACi-related AS events. The dataset GSE132053, which contained the RNA sequence data for 17 HDACi samples, was downloaded and clean reads were aligned to the human GRCh38 genome by hierarchical indexing for spliced alignment of the transcripts, allowing four mismatches. Gene expression levels were evaluated using exons per million fragments mapped for each gene. Student's t-tests were performed to evaluate the significance of changes in ratios for AS events, and regulated alternative splicing events (RASEs) were defined as events with p values less than 0.05. To sort the differentially expressed genes functional categories, Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were identified using the KOBAS 2.0 server. The regulatory mechanisms of the RASEs and RBPs were evaluated using Pearson's correlation coefficient. Seven indirect events of HDACi resistance or sensitivity were identified: NIR_5151_RP11-977G19.10, NIR_4557_IRAG2, NIR_11870_SUMO1, NIR_5347_ING4, NIR_17935_DNAJC2, NIR_17974_CBLL1, and NIR_422_SLC50A1. The potential regulatory relationships between RBPs and HDACi-sensitive RASEs were also analyzed. LEPR and HNRNPAO significantly affected NIR_11870_SUMO1, suggesting a potential regulatory relationship. Additionally, CNN1 may regulate NIR_5347_ING4, CNOT3 may regulate NIR_17935_DNAJC2, and DQX1 and LENG9 may regulate NIR_422_SLC5A1. Overall, our findings establish a theoretical foundation for the precise targeted treatment of CTCLs with HDACi.
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Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.
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Vitiligo is a common immune-related depigmentation condition, and its pathogenesis remains unclear. This study used a combination of bioinformatics methods and expression analysis techniques to explore the relationship between immune cell infiltration and gene expression in vitiligo. Previously reported gene expression microarray data from the skin (GSE53146 and GSE75819) and peripheral blood (GSE80009 and GSE90880) of vitiligo patients and healthy controls was used in the analysis. R software was used to filter the differentially expressed genes (DEGs) in each dataset, and the KOBAS 2.0 server was used to perform functional enrichment analysis. Compared with healthy controls, the upregulated genes in skin lesions and peripheral blood leukocytes of vitiligo patents were highly enriched in immune response pathways and inflammatory response signaling pathways. Immunedeconv software and the EPIC method were used to analyze the expression levels of marker genes to obtain the immune cell population in the samples. In the lesional skin of vitiligo patients, the proportions of macrophages, B cells and NK cells were increased compared with healthy controls. In the peripheral blood of vitiligo patients, CD8+ T cells and macrophages were significantly increased. A coexpression analysis of the cell populations and DEGs showed that differentially expressed immune and inflammation response genes had a strong positive correlation with macrophages. The TLR4 receptor pathway, interferon gamma-mediated signaling pathway and lipopolysaccharide-related pathway were positively correlated with CD4+ T cells. Regarding immune response-related genes, the overexpression of IFITM2, TNFSF10, GZMA, ADAMDEC1, NCF2, ADAR, SIGLEC16, and WIPF2 were related to macrophage abundance, while the overexpression of ICOS, GPR183, RGS1, ILF2 and CD28 were related to CD4+ T cell abundance. GZMA and CXCL10 expression were associated with CD8+ T cell abundance. Regarding inflammatory response-related genes, the overexpression of CEBPB, ADAM8, CXCR3, and TNIP3 promoted macrophage infiltration. Only ADORA1 expression was associated with CD4+ T cell infiltration. ADAM8 and CXCL10 expression were associated with CD8+ T cell abundance. The overexpression of CCL18, CXCL10, FOS, NLRC4, LY96, HCK, MYD88, and KLRG1, which are related to inflammation and immune responses, were associated with macrophage abundance. We also found that immune cells infiltration in vitiligo was associated with antigen presentation-related genes expression. The genes and pathways identified in this study may point to new directions for vitiligo treatment.
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Celiac disease (CD) is an autoimmune intestinal disease caused by the intake of gluten-containing cereals and their products by individuals with genetic susceptibility genes. Vitiligo is a commonly acquired depigmentation of the skin; its clinical manifestation are skin patches caused by localized or generalized melanin deficiency. Both diseases have similar global incidence rates (approximately 1%) and are associated to similar diseases, including autoimmune bullous disease, inflammatory bowel disease, autoimmune thyroiditis, autoimmune gastritis, and type 1 diabetes. The relationship between CD and vitiligo has been reported in several studies, but their conclusions are inconsistent. Further, it has also been reported that a gluten-free diet (GFD) can improve the symptoms of immune-related skin diseases such as vitiligo. In this mini-review, we summarize and review the literature on the relationship between CD and vitiligo, assess the therapeutic significance of GFD for patients with vitiligo, and explore their possible physiopathology. We are hopeful that the information summarized here will assist physicians who treat patients with CD or vitiligo, thereby improving the prognosis.
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Posterior capsule opacification (PCO) after cataract surgery is one of the leading causes of visual impairment and blindness. The cause of PCO is the capsule fibrosis developed on implanted Intraocular Lens (IOLs) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing epithelial mesenchymal transition. How to prevent PCO has been a challenge to scientists and ophthalmologists for decades. Here we demonstrated the use of carboxylated CuInS/ZnS quantum dots (ZCIS QDs), which are free of toxic heavy metals and are more biocompatible, as photothermal nanomedicines. The ZCIS QDs are modified onto the non-optical section of IOLs by a facial activation-immersion method. Under mild NIR laser irradiation, ZCIS QDs modified IOLs (QDs-IOLs) will generate localized heat and prevent the proliferation of LECs onto the surface of QDs-IOLs. Our findings provide experimental evidence for further application of combined nanotechnology and photothermal therapy for the clinical treatment of PCO.
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Aleaciones/química , Opacificación Capsular/terapia , Lentes Intraoculares , Terapia Fototérmica/métodos , Puntos Cuánticos/química , Sulfuros/química , Compuestos de Zinc/química , Animales , Apoptosis , Materiales Biocompatibles , Línea Celular , Supervivencia Celular , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Fibroblastos/efectos de los fármacos , Cristalino/citología , Ratones , Microscopía Electrónica de Transmisión , Cápsula Posterior del CristalinoRESUMEN
Vitiligo is a chronic skin condition lack of melanocytes. However, researches on the aetiology and pathogenesis of vitiligo are still under debate. This study aimed to explore the key genes and pathways associated with occurrence and development of vitiligo.Weighted gene coexpression network analysis (WGCNA) was applied to reanalyze the gene expression dataset GSE65127 systematically. Functional enrichments of these modules were carried out at gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA). Then, a map of regulatory network was delineated according to pivot analysis and drug prediction. In addition, hub genes and crucial pathways were validated by an independent dataset GSE75819. The expressions of hub genes in modules were also tested by quantitative real-time polymerase chain reaction (qRT-PCR).Eight coexpressed modules were identified by WGCNA based on 5794 differentially expressed genes of vitiligo. Three modules were found to be significantly correlated with Lesional, Peri-Lesional, and Non-Lesional, respectively. The persistent maladjusted genes included 269 upregulated genes and 82 downregulated genes. The enrichments showed module genes were implicated in immune response, p53 signaling pathway, etc. According to GSEA and GSVA, dysregulated pathways were activated incessantly from Non-Lesional to Peri-Lesional and then to Lesional, 4 of which were verified by an independent dataset GSE75819. Finally, 42 transcription factors and 228 drugs were spotted. Focusing on the persistent maladjusted genes, a map of regulatory network was delineated. Hub genes (CACTIN, DCTN1, GPR143, HADH, MRPL47, NKTR, NUF2) and transcription factors (ITGAV, SYK, PDPK1) were validated by an independent dataset GSE75819. In addition, hub genes (CACTIN, DCTN1, GPR143, MRPL47, NKTR) were also confirmed by qRT-PCR.The present study, at least, might provide an integrated and in-depth insight for exploring the underlying mechanism of vitiligo and predicting potential diagnostic biomarkers and therapeutic targets.
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Vitíligo/genética , Pueblo Asiatico , Estudios de Casos y Controles , China , Biología Computacional , Bases de Datos Factuales , Perfilación de la Expresión Génica , Humanos , ARN/análisis , Vitíligo/fisiopatologíaRESUMEN
BACKGROUND: Pioglitazone may be beneficial in the treatment of psoriasis. However, based on the effectiveness and safety considerations, it has not been widely used. To fully evaluate the strength of evidence supporting psoriasis treatment with pioglitazone, we conducted a meta-analysis of existing published studies. METHODS: PubMed, Ovid, Cochrane Library, Google Scholar, and Web of Science databases were systematically searched before February 2019. Randomized controlled trials (RCTs) of pioglitazone administration compared with placebo, administered to patients with psoriasis for at least 10 weeks, and published in English were included. Quality of the included RCTs was identified by the modified Jadad scale. The quality of evidence for each outcome was evaluated using the GRADEpro Guideline Development Tool online software. Primary outcomes were proportion of patients showing psoriasis area and severity index (PASI) score improvement (>75%) and the mean percent change in PASI score from baseline to the end of treatment. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI), whereas continuous variables, expressed as mean and standard deviation, were analyzed using the mean differences (MD) with the 95% CI. RESULTS: Six RCTs were analyzed. Meta-analysis showed that pioglitazone reduced the PASI scores in patients with psoriasis compared with the control group when administered at 30 mg per day (Pâ<â0.001, MDâ=â-3.82, 95% CIâ=â-5.70, -1.93) and at 15 mg per day (Pâ=â0.04, MDâ=â-3.53, 95% CIâ=â-6.86, -0.20). The PASI-75 of the pioglitazone group was significantly higher than that of the control group at 30 mg per day (Pâ<â0.001, ORâ=â8.30, 95% CIâ=â3.99, 17.27) and at 15 mg per day (Pâ=â0.03, ORâ=â2.96, 95% CIâ=â1.08, 8.06). No statistically significant differences in total adverse events were observed between the groups. There were no significant differences in common adverse reactions such as weight gain and elevated liver enzymes between the two pioglitazone groups. CONCLUSIONS: Use of pioglitazone in the current treatment of psoriasis is beneficial. The therapeutic effect of the daily 30 mg dose may be greater than that of the 15 mg dose per day with no significant change in the frequency of adverse reactions.
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Pioglitazona/uso terapéutico , Psoriasis/tratamiento farmacológico , Humanos , Pioglitazona/administración & dosificación , Pioglitazona/efectos adversos , Sesgo de Publicación , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Infantile hemangioma (IH) is one of the most common tumors in infants. Its pathogenesis is complex and poorly understood. The risk factors of IH have been extensively studied from clinical and epidemiological perspectives in recent years, but the conclusions in the literature reports are inconsistent. To provide a reference for the prevention of hemangioma, we conducted a meta-analysis of the published studies of potential risk factors for IH. METHODS: The Cochrane Library, Ovid, PubMed, and Web of Science databases were searched systematically. Log odds ratios (log ORs), logistic regression standard errors and 95% confidence intervals (CIs) were used to compare the correlation between IH and potential risk factors. Review Manager 5.3.3 was used for the statistical analysis. RESULTS: Six studies were included and 17 potential risk factors were eventually evaluated. P values < 0.05 were found for female gender (P < 0.01, OR 2.04, 95% CI 1.65-2.51), low birth weight (P < 0.01, OR 4.39, 95% CI 3.05-6.31), multiple gestation (P = 0.01, OR 2.39, 95% CI 1.21-4.71), preterm birth (P = 0.03, OR 2.37, 95% CI 1.07-5.23), progesterone therapy (P < 0.01, OR 2.73, 95% CI 2.12-3.51), and family history (P = 0.01, OR 1.98, 95% CI 1.16-3.38). CONCLUSIONS: This meta-analysis revealed that risk factors, including female gender, low birth weight, multiple gestation, preterm birth, progesterone therapy, and family history may affect the occurrence of IH.
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Hemangioma/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Factores de RiesgoRESUMEN
BACKGROUND: Berberine is a promising natural drug that has a potential therapeutic effect on neurodegenerative diseases. OBJECTIVES: Using U251 cells in vitro, we investigated whether berberine exerts its neuroprotective effect via regulation of CYP2J2. METHOD: After pretreatment with increasing concentrations (1, 3, and 10 µmol/L) of berberine for 0.5 h, U251 cells were stimulated with 1 µg/mL of lipopolysaccharide (LPS). Cell viability was measured 24 h later using a CCK8 kit. mRNA and protein levels of CYP2J2 and peroxisome proliferator-activated receptor alpha (PPARα) were measured by quantitative real-time-polymerase chain reaction and western blotting, respectively, after 24 h of exposure to 1, 3, or 10 µmol/L berberine. Fluorescence immunocytochemistry was also used to evaluate PPARα protein expression after treatment of U251 cells with 10-µmol/L berberine for 24 h. Transient transfection (cotransfection with the plasmid of PPARα- and RXRα-containing) followed by luciferase and chromatin immunoprecipitation assays was used to elucidate the molecular mechanism underlying the observed effects. RESULTS: Compared to the control, LPS-induced U251 cell death was attenuated by berberine in a dose-dependent manner. After 24 h, cell viability was found to be 52.3% (p < 0.05), 66.2% (p < 0.01), and 70.9% (p < 0.001) using 1, 3, and 10 µmol/L berberine treatment, respectively. At these concentrations, berberine increased the CYP2J2 mRNA levels by 1.31-fold (p < 0.05), 1.48-fold (p < 0.01), and 1.88-fold (p < 0.01), respectively, and increased the PPARα mRNA levels 1.17-fold (p < 0.05), 1.29-fold (p < 0.05), and 1.53-fold (p < 0.01), respectively, compared with the respective control groups. In addition, the CYP2J2 and PPARα protein level was also significantly upregulated in U251 cells by berberine (concentrations in 1, 3, and 10 µmol/L) in a dose-dependent manner, compared with the respective control groups. Further investigation indicated that berberine enhances the heterodimerization of PPARα and RXRα, which together bind to the CYP2J2 promoter to induce the expression of CYP2J2 in U251 cells. CONCLUSION: Upon exposure of U251 cells to berberine, CYP2J2 expression is induced as a result of PPARα stimulation, resulting in a neuroprotective effect.
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Berberina/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Glioma/metabolismo , Fármacos Neuroprotectores/farmacología , PPAR alfa/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocromo P-450 CYP2J2 , Sistema Enzimático del Citocromo P-450/genética , Glioma/enzimología , Glioma/genética , Humanos , PPAR alfa/agonistas , PPAR alfa/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Activación Transcripcional/efectos de los fármacosRESUMEN
BACKGROUND: Bowen's disease (BD) is a persistent, progressive intraepidermal carcinoma. BD usually occurs in areas exposed to sunlight. Involvement of the dorsum of the hand is not rare, but that of the palmar aspect is very unusual. Only a few cases have been reported in the literature. CASE SUMMARY: Here, we report the case of a 48-year-old male patient who presented with a history of persistent local erythema lasting for 2 years on the thenar eminence of the left palm. Initially diagnosed as hand eczema, the condition did not improve with intermittent treatment with anti-allergy medications or topical glucocorticoid ointments, among other approaches. Then, the area of erythema gradually enlarged and was accompanied by mild itching. For a definite diagnosis and treatment, the patient came to our hospital. Dermoscopic examination revealed BD, and histopathological examination confirmed the diagnosis. We performed partial resection of the skin lesion followed by photodynamic therapy. No recurrence was observed at the 6-mo follow-up. CONCLUSION: For all atypical palmar lesions, early dermoscopy and/or skin biopsy are needed to avoid missed diagnosis or misdiagnosis.
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BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH;OMIM: #127400) is a rare autosomal dominant skin disease of hyperpigmented and hypopigmented macules on the dorsal aspects of the feet and hands. The adenosine deaminase RNA-Specific (ADAR;OMIM: *146920) gene was identified as causing DSH. Although more than 200 mutations are reported, no research has included the pedigrees of ethnic minorities in China. To investigate clinical features and genetic factors among multi-ethnic families, seven multi-ethnic pedigrees with DSH were collected for analysis of hereditary characteristics and ADAR mutations. METHODS: All 15 exons and exon-intron sequences of the ADAR gene were amplified and Sanger sequenced from 25 patients and 36 normal controls from seven multi-ethnic DSH families with 100 healthy normal controls. Seven mutations were analyzed by Polyphen 2, SIFT and Provean. All mutations in ADAR with DSH were reviewed and genetic and clinical features were summarized for analysis. The ADEAMc domain may be a hot spot of ADAR mutations among patients with DSH. RESULTS: Seven novel mutations were identified in seven multi-ethnic pedigrees: c.497delA(p.Arg105fs), c.3352C>T(p.Gln1058*) and c.3722delT(p.Ser1181fs) were found in three Uygur families with DSH; c.1330A>G(p.Val332Met) and c.2702A>T(p.His841Leu) were found in two Kazakh pedigrees and c.1176G>A(p.Lys326Glu) and c.2861G>A(p.Arg892His) in two Hui pedigrees. We summarized 203 different mutations of ADAR from people with DSH. CONCLUSIONS: Seven novel mutations were identified in seven multi-ethnic families with DSH. Our study expands the genetic spectrum of ADAR mutations in DSH.
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Adenosina Desaminasa/genética , Trastornos de la Pigmentación/congénito , Proteínas de Unión al ARN/genética , Pueblo Asiatico/genética , China , Codón sin Sentido , Análisis Mutacional de ADN , Etnicidad , Exones , Femenino , Mutación del Sistema de Lectura , Humanos , Masculino , Mutación Missense , Linaje , Fenotipo , Trastornos de la Pigmentación/genética , Trastornos de la Pigmentación/patologíaRESUMEN
Repair of UV-induced DNA damage requires chromatin remodeling. How repair is initiated in chromatin remains largely unknown. We recently demonstrated that global genome-nucleotide excision repair (GG-NER) in chromatin is organized into domains in relation to open reading frames. Here, we define these domains, identifying the genomic locations from which repair is initiated. By examining DNA damage-induced changes in the linear structure of nucleosomes at these sites, we demonstrate how chromatin remodeling is initiated during GG-NER. In undamaged cells, we show that the GG-NER complex occupies chromatin, establishing the nucleosome structure at these genomic locations, which we refer to as GG-NER complex binding sites (GCBSs). We demonstrate that these sites are frequently located at genomic boundaries that delineate chromosomally interacting domains (CIDs). These boundaries define domains of higher-order nucleosome-nucleosome interaction. We demonstrate that initiation of GG-NER in chromatin is accompanied by the disruption of dynamic nucleosomes that flank GCBSs by the GG-NER complex.
Asunto(s)
Ensamble y Desensamble de Cromatina/fisiología , Reparación del ADN/fisiología , Regulación Fúngica de la Expresión Génica/fisiología , Genoma Fúngico/fisiología , Nucleosomas , Saccharomyces cerevisiae , Nucleosomas/genética , Nucleosomas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMEN
BACKGROUND: hTERT gene plays an important role in melanoma, although the specific mechanism involved is unclear. The aim of this study was to screen and identify the relative miRNAs with the regulation of hTERT in melanoma. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to detect hTERT mRNA and protein expression in 36 formalin-fixed paraffin-embedded melanoma tissues and 36 age- and sex-matched pigmented nevi cases, respectively. Bioinformatics analysis and custom miRNA polymerase chain reaction array were determined for predicting, screening and verifying miRNAs with the regulation of the hTERT gene. To investigate the biological functions, miRNAs mimics or inhibitors were transfected into melanoma A375 cells. The relative expression of miR-497-5p, miR-195-5p, miR-455-3p and hTERT mRNA was determined by q-PCR. The protein expression of hTERT was detected by Western blot. 3-(4,5-Dimethylthiazolyl-2-yl)-2,5-biphenyl tetrazolium bromide and flow cytometry were employed to detect cell proliferation ability, cell apoptosis and cell cycle. Transwell and wound healing assays were used to observe cell invasion and migration abilities. A direct target gene of miRNAs was analyzed by a dual luciferase reporter activity assay. RESULTS: MiR-497-5p, miR-195-5p, miR-455-3p were significantly downregulated, while hTERT was upregulated in melanoma tissues. hTERT expression level was inversely correlated with miR-497-5p, miR-195-5p and miR-455-3p. Overexpression of miR-497-5p, miR-195-5p and miR-455-3p inhibited A375 cell proliferation, migration and invasion, arrested the cell cycle, induced cell apoptosis and decreased hTERT expression at both mRNA and protein levels. Suppression of miR-497-5p, miR-195-5p and miR-455-3p partially reversed the inhibitory effects. Finally, hTERT was identified as a direct target of miR-497-5p, miR-195-5p and miR-455-3p. CONCLUSIONS: MiR-497-5p, miR-195-5p and miR-455-3p act as tumor suppressors by targeting hTERT in melanoma A375 cells. Therefore, miR-497-5p, miR-195-5p and miR-455-3p could be potential targeted therapeutic choice for melanoma.
RESUMEN
Limited studies have investigated the antiviral efficacy of entecavir (ETV)-based rescue therapy in lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients. We retrospectively analyzed the efficacy of entecavir (ETV) monotherapy versus ETV-tenofovir disoproxil fumarate (TDF) combination therapy in 220 LAM-resistant CHB patients. Among 220 patients, 114 patients were treated with ETV monotherapy and 106 were treated with ETV-TDF combination therapy for at least 24 months. There were no significant differences between the two groups in baseline characteristics. During the follow-up of 24 months, virologic response (VR) occurred in 146 (66.4%) patients (58 patients belonged to the ETV monotherapy group and 88 patients belonged to the ETV-TDF combination group). The VR rates were different between the ETV and ETV-TDF groups (32.5% vs. 57.5% at 6 months, 50.0% vs. 77.4% at 12 months; and 50.9% vs. 83.0% at 24 months, P<0.001). In addition, both groups showed no difference in terms of the biochemical and HBeAg response. The rates of viral breakthrough at 6, 12 and 24 months were significantly different between ETV and ETV-TDF groups (2.63%, 4.39% and 9.65% vs. 0.00%, 0.94% and 1.89% at 6, 12 and 24 months, respectively). The ETV-TDF group was superior to the ETV group in achieving a virologic response. Moreover, the ETV-TDF was lower than the ETV group in achieving the initial viral breakthrough and genotypic mutations. Therefore, ETV-TDF combination therapy might be a better regimen than ETV monotherapy in the subgroup of LAM-resistant Chinese patients with CHB.