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Melasma is a frequently acquired hyperpigmentary skin disorder, for which several therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an effective method, but the recurrence rate of laser treatment is still high. The aim of the present study was to elucidate the mechanism of the high relapse rate of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin and non-lesional skin were evaluated by means of a reflectance confocal laser scanning microscope before and after laser treatment. Melanin content and transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction tester accordingly. The melanin index value was significantly decreased in the lesional skin after laser treatment, while the non-lesional skin had no difference. The dendritic cells were observed at the level of the dermal-epidermal junction (DEJ) in the lesions of 8 patients before laser treatment, while after laser treatment, the dendritic cells were observed in all 25 subjects. Moreover, there was significant difference between the TEWL value of the lesions before and after laser treatment. Furthermore, the TEWL value was higher in lesions of the 8 subjects which had dendritic cells compared with other 17 subjects which had no dendritic cells, no matter before or after laser treatment. The relapse patients of melasma had higher TEWL value compared with the non-relapse patients. Melanocyte activation and skin barrier disruption may be related to the high relapse rate of melasma after laser treatment.
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Láseres de Estado Sólido , Melanocitos/patología , Melanosis/patología , Melanosis/radioterapia , Piel/patología , Adulto , Células Dendríticas/metabolismo , Femenino , Humanos , Láseres de Estado Sólido/efectos adversos , Terapia por Luz de Baja Intensidad , Melaninas/metabolismo , Piel/efectos de la radiación , Pérdida Insensible de AguaRESUMEN
Sleep disturbance is a significant problem affecting around 50% of cancer patients. Non-pharmacological interventions can be used to improve sleep quality in cancer patients, but little is known about the feasibility, acceptability, and effectiveness of auricular point acupressure (APA) to reduce sleep disturbance in women with ovarian cancer undergoing chemotherapy. A pilot randomized controlled trial was conducted at a publicly funded hospital in southern Taiwan. Fifty-five eligible women were approached and 47 women participated. Women randomly assigned to the control group (n = 24) received sleep hygiene practices alone. Women in the intervention group (n = 23) received sleep hygiene practices and APA treatment which involved gentle fingertip pressure at acupoints on the external ear. The Pittsburgh Sleep Quality Index (PSQI) was completed at four time points. Forty women completed the trial giving a retention rate of 85%. Women receiving the intervention reported a 65% reduction in sleep disturbance according to PSQI global scores from Time 1 (mean = 13.2) to Time 2 (mean = 4.65) after 4 weeks of APA treatment. There was a further 10% decrease in PSQI scores at Time 3 (mean = 4.21) after 6 weeks of APA treatment. Compared to controls, women receiving APA had significantly lower PSQI mean global scores at both Time 2 and Time 3 (p < .001). APA treatment for women with ovarian cancer produced significantly improved sleep. Participants found the procedure easy to perform. Pilot findings support the feasibility of a longitudinal study with a larger, representative sample.
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Acupresión/métodos , Puntos de Acupuntura , Neoplasias Ováricas/complicaciones , Trastornos del Sueño-Vigilia/terapia , Sueño/fisiología , Adulto , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/psicología , Proyectos Piloto , Trastornos del Sueño-Vigilia/etiología , Resultado del TratamientoRESUMEN
Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.
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Seeking novel high-performance elastocaloric materials with low critical stress plays a crucial role in advancing the development of elastocaloric refrigeration technology. Here, as a first attempt, the elastocaloric effect of TiZrNbAl shape memory alloy at both room temperature and finite temperatures ranging from 245 K to 405 K, is studied systematically. Composition optimization shows that Ti-19Zr-14Nb-1Al (at.%), possessing excellent room-temperature superelasticity with a critical stress of around 100 MPa and a small stress hysteresis of around 70 MPa and outstanding fracture resistance with a compressive strain of 20% and stress of 1.7 GPa, demonstrates a substantial advantage as an elastocaloric refrigerant. At room temperature, a large adiabatic temperature change (ΔTad) of -6.7 K is detected, which is comparable to the highest value reported in the Ti-based alloys. A high elastocaloric cyclic stability, with almost no degradation of ΔTad after 4000 cycles, is observed. Furthermore, the sizeable elastocaloric effect can be steadily expanded from 255 K to 395 K with a temperature window of as large as 140 K. A maximum ΔTad of -7.9 K appears at 355 K. The present work demonstrates a promising potential of TiZrNbAl as a low critical stress and low hysteresis elastocaloric refrigerant.
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Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.
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Inmunoterapia , Terapia Neoadyuvante , Piroptosis , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patología , Terapia Neoadyuvante/métodos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Masculino , Pronóstico , Femenino , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , MultiómicaRESUMEN
A novel broadband emission phosphor Sr(3-2x) Li(1+ x) MgV3 O12 : xEu3+ was synthesized by a solid-state reaction method. Then discussed the luminous property under the influence of temperature and doping density of Eu3+, was discussed. X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence spectra were used to characterize the feature of Sr(3-2x)Li(1+x)MgV3O12 : xEu3+. The excitation and emission spectra exhibit that the phosphor of Sr(3-2x) Li(1 + x) MgV3O12 : xEu3+ matches with nearly ultraviolet chip. The emission band covers from 450 to 630 nm, which shows that the phosphor is promising single-phase phosphors for white LED.
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Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms. Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions. Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p. Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.
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Neoplasias del Colon , MicroARNs , Humanos , Femenino , MicroARNs/genética , Neoplasias del Colon/epidemiología , Neoplasias del Colon/genética , Obesidad/complicaciones , Obesidad/genética , Biología Computacional , Bases de Datos Factuales , Proteínas RepresorasRESUMEN
The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.
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Quimiocina CCL5 , Neoplasias Colorrectales , Humanos , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD.
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Ovarian cancer patients frequently develop resistance to chemotherapy regiments using Taxol and carboplatin. One of the resistance factors that protects cancer cells from Taxol-based therapy is multidrug resistance 1 (MDR1). micro(mi)RNAs are small noncoding RNAs that negatively regulate protein expression. Members of the let-7 family of miRNAs are downregulated in many human cancers, and low let-7 expression has been correlated with resistance to microtubule targeting drugs (Taxanes), although little is known that would explain this activity. We now provide evidence that, although let-7 is not a universal sensitizer of cancer cells to Taxanes, it affects acquired resistance of cells to this class of drugs by targeting IMP-1, resulting in destabilization of the mRNA of MDR1. Introducing let-7g into ADR-RES cells expressing both IMP-1 and MDR1 reduced expression of both proteins rendering the cells more sensitive to treatment with either Taxol or vinblastine without affecting the sensitivity of the cells to carboplatin, a non-MDR1 substrate. This effect could be reversed by reintroducing IMP-1 into let-7g high/MDR1 low cells causing MDR1 to again become stabilized. Consistently, many relapsed ovarian cancer patients tested before and after chemotherapy were found to downregulate let-7 and to co-upregulate IMP-1 and MDR1, and the increase in the expression levels of both proteins after chemotherapy negatively correlated with disease-free time before recurrence. Our data point at IMP-1 and MDR1 as indicators for response to therapy, and at IMP-1 as a novel therapeutic target for overcoming multidrug resistance of ovarian cancer.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , MicroARNs/genética , Neoplasias Ováricas/genética , Proteínas de Unión al ARN/genética , Taxoides/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Western Blotting , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Células HeLa , Humanos , Inmunohistoquímica , Hibridación in Situ , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Taxoides/uso terapéuticoRESUMEN
Spinal cord injury is a severe central nervous system disease, which will cause a series of complex pathophysiological changes and activate a variety of signaling pathways including Notch signaling. Studies have evidenced that activation of the Notch signaling pathway is not conducive to nerve repair and symptom improvement after spinal cord injury. Its mechanisms include inhibiting neuronal differentiation and axon regeneration, promoting reactive astrocyte proliferation, promoting M1 macrophage polarization and the release of proinflammatory factors, and inhibiting angiogenesis. Therefore, it has become a promising therapeutic strategy to inhibit Notch signal as a target in the treatment of spinal cord injury. In recent years, some researchers have used drugs, cell transplantation or genetic modification to regulate Notch signaling, which can promote the recovery of nerve function after spinal cord injury, thereby providing new treatment strategies for the treatment of spinal cord injury. This article will summarize the mechanism of Notch signaling pathway in spinal cord injury, and at the same time review the research progress in the treatment of spinal cord injury by modulating Notch signaling pathway in recent years, so as to provide new research ideas for further exploring new strategies for spinal cord injury.
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Axones , Traumatismos de la Médula Espinal , Axones/metabolismo , Trasplante de Células , Humanos , Regeneración Nerviosa , Transducción de Señal/genética , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/metabolismoRESUMEN
BACKGROUND: Methamphetamine (METH) abuse causes serious health problems, including injury to the immune system, leading to increased incidence of infections and even making withdrawal more difficult. Of course, immune cells, an important part of the immune system, are also injured in methamphetamine abuse. However, due to different research models and the lack of bioinformatics, the mechanism of METH injury to immune cells has not been clarified. METHODS: We examined the response of three common immune cell lines, namely Jurkat, NK-92 and THP-1 cell lines, to methamphetamine by cell viability and apoptosis assay in vitro, and examined their response patterns at the mRNA level by RNA-sequencing. Differential expression analysis of two conditions (control and METH treatment) in three types of immune cells was performed using the DESeq2 R package (1.20.0). And some of the differentially expressed genes were verified by qPCR. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes by the clusterProfiler R package (3.14.3). And gene enrichment analysis was also performed using MetaScape ( www.metascape.org ). RESULTS: The viability of the three immune cells was differentially affected by methamphetamine, and the rate of NK-cell apoptosis was significantly increased. At the mRNA level, we found disorders of cholesterol metabolism in Jurkat cells, activation of ERK1 and ERK2 cascade in NK-92 cells, and disruption of calcium transport channels in THP-1 cells. In addition, all three cells showed changes in the phospholipid metabolic process. CONCLUSIONS: The results suggest that both innate and adaptive immune cells are affected by METH abuse, and there may be commonalities between different immune cells at the transcriptome level. These results provide new insights into the potential effects by which METH injures the immune cells.
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Metanfetamina , Ontología de Genes , Humanos , Metanfetamina/efectos adversos , ARN Mensajero/genética , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
Recent miRNA transfection experiments show strong evidence that miRNAs influence not only their target but also non-target genes; the precise mechanism of the extended regulatory effects of miRNAs remains to be elucidated. A hypothetical two-layer regulatory network in which transcription factors (TFs) function as important mediators of miRNA-initiated regulatory effects was envisioned, and a comprehensive strategy was developed to map such miRNA-centered regulatory cascades. Given gene expression profiles after miRNA-perturbation, along with putative miRNA-gene and TF-gene regulatory relationships, highly likely degraded targets were fetched by a non-parametric statistical test; miRNA-regulated TFs and their downstream targets were mined out through linear regression modeling. When applied to 53 expression datasets, this strategy discovered combinatorial regulatory networks centered around 19 miRNAs. A tumor-related regulatory network was diagrammed as an example, with the important tumor-related regulators TP53 and MYC playing hub connector roles. A web server is provided for query and analysis of all reported data in this article. Our results reinforce the growing awareness that non-coding RNAs may play key roles in the transcription regulatory network. Our strategy could be applied to reveal conditional regulatory pathways in many more cellular contexts.
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Redes Reguladoras de Genes , MicroARNs/metabolismo , Interferencia de ARN , Factores de Transcripción/metabolismo , Algoritmos , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos LinealesRESUMEN
Gastrointestinal probiotics play an important role in maintaining intestinal bacteria homeostasis. They might benefit people with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which remains a global health challenge. However, there is a controversy regarding the efficacy of probiotics for the treatment of AIDS. This study systematically reviewed the evidence of the effects of existing probiotic interventions on AIDS and sought to provide information on the role of probiotics in the treatment of HIV/AIDS patients. A meta-analysis of studies identified by screening multiple databases was performed using a fixed-effects model in Review Manager 5.2 software. The meta-analysis showed that probiotics could reduce the incidence of AIDS-related diarrhea (RR = 0.60 (95% CI: 0.44-0.82), p = 0.001). The short-term use of probiotics (supplementation duration shorter than 30 days) did not reduce the incidence of diarrhea (RR = 0.76 (95% CI: 0.51-1.14), p = 0.19), while the long-term use of probiotics (supplementation duration longer than 30 days) reduced diarrhea (RR = 0.47 (95% CI: 0.29-0.76), p = 0.002). Probiotics had no effect on CD4 cell counts in HIV/AIDS patients (MD = 21.24 (95% CI: -12.95-55.39), p = 0.22). Our data support that probiotics were associated with an obvious reduction in AIDS-related diarrhea, which indicates the need for additional research on this potential preventive strategy for AIDS.
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The skin barrier of melasma is involved in the pathogenesis of melasma. Previous studies have shown that there are differences in the expression of epidermal lipid genes in melasma, but little is known about the epidermis lipid composition of melasma. Compared with the non-lesional skin, the content of total lipids, phosphatidic acid, phosphatidylserine, and ceramide (Cer) increased significantly in the lesional skin. Multivariate data analysis indicated that 40 individual Cer lipid species were responsible for the discrimination. In terms of acyl chain length in Cer, the expressions of very long chain (VLC) (C20-C26) and ultra-long chain (ULC) (>C26) increased significantly in the lesional skin. However, Cer[AH] had negative correlations with the activation of melanocytes in the lesional skin. Some lipid species had lower expression in lesional skin with high activation of melanocytes, as well as the high darkness. The epidermal thickness of lesional skin was higher compared with the non-lesional skin. These results suggest that Cer increased significantly in the lesional skin of melasma, possibly as a compensatory mechanism to maintain skin barrier function. Between different groups of darkness and activation of melanocytes, the change of ceramides might have correlation with the pigmentation progress of melasma.
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Epidermis/metabolismo , Metabolismo de los Lípidos , Lipidómica , Melanocitos/metabolismo , Melanosis/metabolismo , Síndromes Neurocutáneos/metabolismo , Epidermis/patología , Femenino , Humanos , Melanocitos/patología , Melanosis/patología , Síndromes Neurocutáneos/patologíaRESUMEN
1,2-Annulated pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) 6a-6k, 8a-8b and 9 have been synthesized by one pot tandem reactions of 2-acetyl-N-phenacylpyridinium bromides (1a-1d) with electron-deficient cyclic alkenes (N-alkyl(aryl)maleimides, benzoquinones and naphthoquinone) in the presence of sodium carbonate as a base and tetrakispyridinecobalt(II) dichromate (TPCD) as an oxidant. These products are formed by 1.3-dipolar cycloaddition of the 1-oxoquinolizinium ylides generated in situ from 1a-1d with the alkene followed by dehydrogenation of the primary cycloadduct under the action of TPCD. Similar reactions of the ylides generated in situ from 1a-1f with maleic anhydride gave the 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones 7a-7f via oxidative bisdecarboxylation and dehydrogenation of the primary cycloadducts under the action of TPCD.
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BACKGROUND: MicroRNAs (miRNAs) are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. RESULTS: In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values < 0.05. The results indicated that the miRNA profiles were different in neural and non-neural tissues. In total, we found 30 miRNAs that were specifically expressed in neural tissues. For example, miR-199a was specifically expressed in neural tissues. Of these, the expression patterns of four miRNAs were comparable with those of Landgraf et al., Bak et al., and Kapsimani et al. Thirty neural tissue-specific miRNAs were chosen to predict target genes. A total of 1,475 target mRNA were predicted based on the intersection of three public databases, and target mRNA's pathway, function, and regulatory network analysis were performed. We focused on target enrichments of the dorsal root ganglion (DRG) and olfactory bulb. There were four Gene Ontology (GO) functions and five KEGG pathways significantly enriched in DRG. Only one GO function was significantly enriched in the olfactory bulb. These targets are all predictions and have not been experimentally validated. CONCLUSION: Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.
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Perfilación de la Expresión Génica/métodos , MicroARNs/genética , Tejido Nervioso/metabolismo , Análisis de Secuencia de ARN/métodos , Animales , Análisis por Conglomerados , Biología Computacional , Ganglios Espinales/metabolismo , Expresión Génica , Bulbo Olfatorio/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Componente Principal , Ratas , Programas InformáticosRESUMEN
We performed this study to reassess the prognostic factors of diffuse large B-cell lymphoma (DLBCL) in the era of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Chinese population. One hundred and twenty-five consecutive patients with DLBCL were enrolled in this study from February 2000 to September 2006. They had received six courses of R-CHOP regimen consisting of rituximab 375 mg/m(2), intravenously, D1; cyclophosphamide 750 mg/m(2), bolus infusion, D2; doxorubicin 50 mg/m(2), bolus infusion, D2; vincristine 1.4 mg/m(2), bolus infusion, D2; and prednisone 60 mg, orally, D2-6. All the patients were evaluated and followed-up after the treatment. Eighty-six out of 125 enrolled patients (68.8%) achieved complete response (CR), 16 patients (12.8%) achieved partial response (PR), 11 patients (12.8%) achieved stable disease, and 12 patients (9.6%) experienced progressive disease (PD). In univariate analysis, IPI factors, except for age, was correlated with the treatment outcome of complete remission; however, only early clinical stages and absence of bulky disease was statistically significantly associated with the better CR rate. Lactate dehydrogenase (LDH), extranodal diseases, bulky disease, and obtaining CR after completion of four courses of treatment was correlated with TTF (P = 0.038, 0.044, 0.034, and 0.000, respectively); performance status, LDH level, number of extranodal diseases, and obtaining CR after completion four courses of treatment significantly influenced OS (P = 0.027, 0.000, 0.019, and 0.000, respectively); and presence of bulky disease and obtaining CR at the end of fourth cycle of treatment were significantly correlated with DFS in multivariate analysis (P = 0.006 and 0.001, respectively) in Cox regression. IPI is still important in predicting the prognosis in the R-CHOP era in DLBCL; however, obtaining CR after four cycles of R-CHOP and presence of bulky disease should be considered together.
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Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Rituximab , Vincristina/uso terapéutico , Adulto JovenRESUMEN
To understand how molecular damage under harsh environmental conditions can be controlled, we investigated the properties of ATPase activity of the chaperonin molecular machinery from the hyperthermophilic archaeon Pyrococcus furiosus (PfCPN). PfCPN ATPase activity depended on K(+) and Mg(2+) and its optimal pH was 7.5. PfCPN had almost no ADPase activity. ADP strongly competitively inhibited PfCPN ATPase activity. Inhibition of PfCPN ATPase decreased its chaperonin activity in protecting lysozyme from heat-induced inactivation.
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Adenosina Trifosfatasas/metabolismo , Proteínas Arqueales/metabolismo , Chaperoninas/metabolismo , Pyrococcus furiosus/enzimología , Temperatura , Adenosina Difosfato/farmacología , Adenosina Monofosfato/farmacología , Adenosina Trifosfatasas/antagonistas & inhibidores , Cationes Bivalentes/farmacología , Cationes Monovalentes/farmacología , Chaperoninas/antagonistas & inhibidores , Concentración de Iones de Hidrógeno/efectos de los fármacos , Magnesio/farmacología , Potasio/farmacología , Pyrococcus furiosus/efectos de los fármacos , Especificidad por Sustrato/efectos de los fármacosRESUMEN
MicroRNAs (miRNAs) are a group of RNAs that play important roles in regulating gene expression and protein translation. In a previous study, we established an oligonucleotide microarray platform to detect miRNA expression. Because it contained only hundreds of probes, data normalization was difficult. In this study, the microarray data for eight miRNAs extracted from inflamed rat dorsal root ganglion (DRG) tissue were normalized using 15 methods and compared with the results of real-time polymerase chain reaction. It was found that the miRNA microarray data normalized by the print-tip loess method were the most consistent with results from real-time polymerase chain reaction. Moreover, the same pattern was also observed in 14 different types of rat tissue. This study compares a variety of normalization methods and will be helpful in the preprocessing of miRNA microarray data.