Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Med Chem ; 245(Pt 1): 114898, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36370552

RESUMO

50 New drugs including 36 chemical entities and 14 biologics were approved by the U.S. Food and Drug Administration during 2021. Among the marketed drugs, 31 new small molecule agents (29 small molecule drugs and 2 diagnostic agents) with privileged structures and novel clinical applications represent as promising leads for the development of new drugs with the similar indications and improved therapeutic efficacy. This review is mainly focused on the clinical applications and synthetic methods of 29 small molecule drugs newly approved by the FDA in 2021. We believed that insight into the synthetic approaches of drug molecules would provide creative and practical inspirations for the development of more efficient and practical synthetic technologies to meet with new drug discovery.


Assuntos
Produtos Biológicos , Aprovação de Drogas , Estados Unidos , United States Food and Drug Administration , Preparações Farmacêuticas/química , Descoberta de Drogas , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química
2.
Neural Regen Res ; 18(6): 1300-1307, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36453415

RESUMO

In Alzheimer's disease, the transporter P-glycoprotein is responsible for the clearance of amyloid-ß in the brain. Amyloid-ß correlates with the sphingomyelin metabolism, and sphingomyelin participates in the regulation of P-glycoprotein. The amyloid cascade hypothesis describes amyloid-ß as the central cause of Alzheimer's disease neuropathology. Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-ß and their potential association in the pathological process of Alzheimer's disease is critical. Herein, we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age. The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age. Decreased sphingomyelin levels, increased ceramide levels, and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice. Similar results were observed in the Alzheimer's disease mouse model induced by intracerebroventricular injection of amyloid-ß1-42 and human cerebral microvascular endothelial cells treated with amyloid-ß1-42. In human cerebral microvascular endothelial cells, neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-ß1-42 treatment. Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide. Together, these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway. These studies may serve as new pursuits for the development of anti-Alzheimer's disease drugs.

3.
Front Pharmacol ; 13: 1041671, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457713

RESUMO

Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model in vivo. CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4+, activated CD8+ T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.

4.
Proc Natl Acad Sci U S A ; 119(49): e2208904119, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36445966

RESUMO

The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.


Assuntos
Neuroblastoma , RNA Longo não Codificante , Humanos , Reparo do DNA por Junção de Extremidades/genética , Quebras de DNA de Cadeia Dupla , RNA Longo não Codificante/genética , Reparo do DNA/genética , DNA , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-36267087

RESUMO

Background: Eucommia ulmoides Oliver (EU) is a plant used in Chinese medicine as a medicinal herb to treat autoimmune and inflammatory conditions. We used network pharmacology to examine the active ingredients and estimate the main targets and pathways affected by EU when it is used to treat ankylosing spondylitis (AS). Materials and Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search for active ingredients in EU and their target proteins. The GeneCards Database was used to find AS-related targets. The targets from the EU and AS searches that coincided were selected by constructing a Venn diagram. Then, a STRING network platform and Cytoscape software were used to analyse the protein-protein interaction (PPI) network and key targets. The strong affinity between EU and its targets was confirmed using molecular docking techniques. The Gene Ontology and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapping targets was performed using the database for annotation, visualization, and integrated discovery online tool. Results: The number of active ingredients against AS in EU was discovered to be 28. Major targets against AS in the PPI network and core targets analyses were identified as IL-1B, PTGS2, IL-8, nMMP-9, CCL2, MYC, and IL-2. Furthermore, molecular docking studies showed the strong affinity between EU's bioactive molecules and their AS targets. Enrichment analysis revealed that active ingredients from EU were involved in a variety of biological processes, including the response to molecules derived from bacteria, extracellular stimuli, nutrient levels, and the regulation of reactive oxygen species, all of which are mediated by interleukin-17, TNF-α, and other signalling pathways. Conclusion: The therapy for AS using EU involves a multitarget, multipathway, and multiselection mechanism that includes anti-inflammatory and analgesic effects. This study provides a theoretical basis for future research into targeted molecular therapies for AS.

6.
Huan Jing Ke Xue ; 43(9): 4831-4838, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096623

RESUMO

Arsenic (As) pollution has a toxic effect on crop growth, leading to reduced crop quality and yield. Therefore, it is urgent to explore safe and effective strategies to reduce its toxicity. In this experiment, hydroponics, fluorescent probe locating technology, differential centrifugation, and Fourier infrared spectroscopy (FTIR) analysis were used to research the effect of exogenous jasmonic acid (JA) on the accumulation and stress resistance of rice seedlings. The results showed that JA application reduced the As content in the roots and shoots of rice by 31.4% and 51.4%, respectively, and significantly reduced As content in the cell wall and soluble fractions of rice roots. JA changed the distribution ratio of As in the subcellular components. The distribution ratio of As in the cell wall increased by 16.4%, and the distribution ratio of soluble fractions decreased by 17.3%. JA enhanced the fixation of As by the cell wall and reduced the As content in the soluble fraction. Furthermore, JA increased the levels of SOD, CAT, GSH, and PEPC in root cells and reduced the contents of H2O2 and MDA, indicating that JA reduced lipid peroxidation damage, regulated carbon and nitrogen metabolism, and alleviated As toxicity. This research provides a new approach for the prevention and control of rice As pollution.


Assuntos
Arsênio , Oryza , Arsênio/metabolismo , Ciclopentanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Oxilipinas , Plântula
7.
Huan Jing Ke Xue ; 43(8): 4292-4300, 2022 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-35971725

RESUMO

In order to improve the phytoextraction efficiency of Xanthium sibiricum on farmland soil that had been contaminated by Cd and As, this study explored the effects of chelating agents and organic acids (EDTA, SAP, CA, and MA) on the extraction of Cd and As heavy metals using X. sibiricum. The results showed that the four different chelating agents and organic acids had little effect on the biomass of the roots, stems, and leaves of X. sibiricum. However, they had different effects on the concentrations and accumulation of Cd and As in various organs of X. sibiricum. Compared with the those in the CK treatment, EDTA, SAP, CA, and MA significantly increased the Cd concentrations in the leaves of X. sibiricum by 44.1%, 32.4%, 41.2%, and 38.2% and the As concentrations in the roots of X. sibiricum by 89.6%, 7.4%, 94.8%, and 61.5%, respectively. The four treatments (EDTA, SAP, CA, and MA) improved the total Cd accumulation of X. sibiricum, with increasing ranges, respectively, of 70.2%, 29.4%, 28.9%, and 33.1%, and the As accumulation increased by 67.0%, 19.6%, 81.9%, and 40.8%, respectively, compared with that of the CK treatment. The four chelating agents and organic acids had different effects on the Cd and As bioconcentration factor and transfer factor of various organs of X. sibiricum. Treatments with EDTA, SAP, CA, and MA resulted in a decrease of 32.7%-38.2% in soil Cd concentrations and a decrease of 14.6%-20.5% in soil As concentrations. These four chelating agents can be used for enhancing the efficiency of extraction Cd and As heavy metals by X. sibiricum.


Assuntos
Arsênio , Metais Pesados , Poluentes do Solo , Xanthium , Biodegradação Ambiental , Cádmio/análise , Quelantes/farmacologia , Ácido Edético/farmacologia , Metais Pesados/análise , Solo , Poluentes do Solo/análise
8.
J Fungi (Basel) ; 8(7)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35887475

RESUMO

Pleosporales is the largest and most morphologically diverse order in Dothideomycetes, including a large proportion of saprobic fungi. During the investigation of microfungi from decaying wood in Sichuan Province, several novel fungal taxa of asexual and sexual morphs were collected, identified, and well-described. Phylogenetic analyses based on SSU, ITS, LSU, RPB2 and TEF1α gene sequences suggested that these new taxa were related to Pleosporales and distributed in five families, viz. Amorosiaceae, Bambusicolaceae, Lophiostomataceae, Occultibambusaceae and Tetraplosphaeriaceae. The morphological comparison and molecular phylogeny evidence justify the establishment of six new taxa, namely Bambusicola guttulata sp. nov., Flabellascoma sichuanense sp. nov., Neoangustimassarina sichuanensis gen. et sp. nov., Occultibambusa sichuanensis sp. nov. and Pseudotetraploa bambusicola sp. nov. Among them, Neoangustimassarina was introduced as the second sexual morph genus in Amorosiaceae; Bambusicola guttulata, O. sichuanensis and P. bambusicola were isolated from bamboos, which contributed to the diversity of bambusicolous fungi. The detailed, illustrated descriptions and notes for each new taxon are provided, as well as a brief note for each family. The potential richness of fungal diversity in Sichuan Province is also discussed.

9.
Life (Basel) ; 12(7)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35888046

RESUMO

Complete ammonia oxidizers (comammox), which directly oxidize ammonia to nitrate, were recently identified and found to be ubiquitous in artificial systems. Research on the abundance and niche differentiation of comammox in the sludges of wastewater treatment plants (WWTPs) would be useful for improving the nitrogen removal efficiency of WWTPs. Here, we investigated the relative abundance and diversity of comammox in fifteen sludges of five WWTPs that use the anaerobic-anoxic-aerobic process in Jinan, China, via quantitative polymerase chain reaction and high-throughput sequencing of the 16S rRNA gene and ammonia monooxygenase gene. In the activated sludges in the WWTPs, comammox clade A.1 was widely distributed and mostly comprised Candidatus Nitrospira nitrosa-like comammox (>98% of all comammox). The proportion of this clade was negatively correlated (p < 0.01) with the dissolved oxygen (DO) level (1.7-8 mg/L), and slight pH changes (7.20-7.70) affected the structure of the comammox populations. Nitrospira lineage I frequently coexisted with Nitrosomonas, which generally had a significant positive correlation (p < 0.05) with the DO level. Our study provided an insight into the structure of comammox and other nitrifier populations in WWTPs that use the anaerobic-anoxic-aerobic process, broadening the knowledge about the effects of DO on comammox and other nitrifiers.

10.
Bioorg Chem ; 127: 105908, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35728291

RESUMO

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 µM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.


Assuntos
Antineoplásicos , Diosgenina , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Diosgenina/farmacologia , Desenho de Fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
11.
Gels ; 8(5)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35621618

RESUMO

Silica aerogel composite is an excellent thermal insulator for spacecraft under high-temperature and complex air environments. This study intends to evaluate SiC-doped silica aerogel's thermal insulation performance under large temperature and air pressure differences. In this paper, the hot surface's temperature response of SiC-doped silica aerogel with different content was studied at significant temperature differences (ΔT) when pressure changes instantaneously. Their thermal insulation performance was evaluated by analyzing the influence of pressure gradients on the unsteady-state heat transfer. When the cold surface's temperature of the specimen keeps constant at 15 °C and ΔT = 171~912 K, the results demonstrate that the correlative thermal conductivities of silica aerogel with 1% and 5.84% SiC are 0.02223~0.04077 W·m-1·K-1 at P ≈ 10 Pa and 0.03165~0.04665 W·m-1·K-1 at P = 1 atm, respectively. The aerogel composite with 0% SiC showed the best thermal insulation performance at ΔT < 200 K and P ≈ 10 Pa, while the aerogel with 5.84% SiC became the best at ΔT > 700 K and P = 1 atm. In addition, the transient pressure decreases will significantly impair the heat transfer of the gas inside the aerogel, thereby weakening the gaseous thermal conductivity and improving the thermal insulation performance.

12.
Ecol Evol ; 12(4): e8837, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35449584

RESUMO

The process of phenotypic adaptation to the environments is widely recognized. However, comprehensive studies integrating phylogenetic, phenotypic, and ecological approaches to assess this process are scarce. Our study aims to assess whether local adaptation may explain intraspecific differentiation by quantifying multidimensional differences among populations in closely related lucanid species, Platycerus delicatulus and Platycerus kawadai, which are endemic saproxylic beetles in Japan. First, we determined intraspecific analysis units based on nuclear and mitochondrial gene analyses of Platycerus delicatulus and Platycerus kawadai under sympatric and allopatric conditions. Then, we compared differences in morphology and environmental niche between populations (analysis units) within species. We examined the relationship between morphology and environmental niche via geographic distance. P. kawadai was subdivided into the "No introgression" and "Introgression" populations based on mitochondrial COI gene - nuclear ITS region discordance. P. delicatulus was subdivided into "Allopatric" and "Sympatric" populations. Body length differed significantly among the populations of each species. For P. delicatulus, character displacement was suggested. For P. kawadai, the morphological difference was likely caused by geographic distance or genetic divergence rather than environmental differences. The finding showed that the observed mitochondrial-nuclear discordance is likely due to historical mitochondrial introgression following a range of expansion. Our results show that morphological variation among populations of P. delicatulus and P. kawadai reflects an ecological adaptation process based on interspecific interactions, geographic distance, or genetic divergence. Our results will deepen understanding of ecological specialization processes across the distribution and adaptation of species in natural systems.

13.
Neurol Sci ; 43(4): 2785-2790, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34709479

RESUMO

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disorder whose main symptoms are muscle weakness and fatigue. Irisin is a novel skeletal muscle-derived myokine participating in several physiological and pathological processes. The initial objective of the project was to explore serum levels of irisin in patients with MG, as well as its correlation with disease severity. METHODS: We retrospectively evaluated serum levels of irisin in 77 MG patients and 57 healthy controls (HCs) by enzyme-linked immunosorbent assay. Further, clinical parameters were measured properly. RESULTS: Serum irisin levels were significantly elevated in MG patients compared with HCs (p < 0.001). Furthermore, serum irisin levels were associated with the myasthenia gravis activities of daily living score in ocular myasthenia gravis (OMG) patients (r = 0.476, p = 0.004), but there was no relationship to be considered of any relevant value in generalized myasthenia gravis (GMG) patients. Acetylcholine receptor antibody-positive MG patients had higher serum irisin levels compared with HCs. Thymoma, endotracheal intubation, or intensive care unit treatments subsequently were not found to have effect on serum levels of irisin, but tendencies of increase were observed in negative ones. CONCLUSIONS: Serum irisin levels were elevated in patients with MG, suggesting its possible involvement in MG. And irisin is expected to be a signal to evaluate the activities of daily living of OMG patients, while its effect needs further study.


Assuntos
Atividades Cotidianas , Fibronectinas , Miastenia Gravis , Autoanticorpos/sangue , Fibronectinas/sangue , Humanos , Miastenia Gravis/sangue , Miastenia Gravis/diagnóstico , Receptores Colinérgicos/imunologia , Estudos Retrospectivos
14.
Front Microbiol ; 12: 794904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970248

RESUMO

To deepen understanding the evolutionary process of lucanid-yeast association, the lateral transmission process of yeast symbionts among stag beetle genera Platycerus and Prismognathus around the border between Japan and South Korea was estimated based on molecular analyses and species distribution modelings. Phylogenetic analyses were based on yeast ITS and IGS sequences and beetle COI sequences using Prismognathus dauricus from the Tsushima Islands and Pr. angularis from Kyushu, Japan, as well as other sequence data from our previous studies. The range overlap based on the species distribution model (SDM) and differentiation in ecological space were analyzed. Based on the IGS sequences, Clade II yeast symbionts were shared by Platycerus hongwonpyoi and Pr. dauricus in South Korea and the Tsushima Islands, and Platycerus viridicuprus in Japan. Clade III yeasts were shared by Pr. dauricus from the Tsushima Islands and Pr. angularis in Japan. During the Last Interglacial period when the land bridge between Japan and the Korean Peninsula existed, range overlap was predicted to occur between Pl. viridicuprus and Pr. dauricus in Kyushu and between Pr. dauricus and Pr. angularis in Kyushu and the Tsushima Islands. The ecological space of Pl. hongwonpyoi was differentiated from that of Pl. viridicuprus and Pr. angularis. We demonstrated the paleogeographical lateral transmission process of Scheffersomyces yeast symbionts among lucanid genera and species: putative transmission of yeasts from Pr. dauricus to Pl. viridicuprus in Kyushu and from Pr. angularis to Pr. dauricus in Kyushu or the Tsushima Islands. We also found that the yeast symbionts are likely being replaced in Pr. dauricus on the Tsushima Islands. We present novel estimates of the lateral transmission process of microbial symbionts based on phylogenetic, SDM and environmental analyses among lucanid beetles.

15.
Clin Exp Immunol ; 206(2): 208-215, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34428306

RESUMO

Irisin is a novel hormone-like myokine that plays an important role in central nervous system (CNS) diseases, such as cerebral ischaemia and Alzheimer's disease. However, irisin is rarely investigated in multiple sclerosis (MS), a typical inflammatory demyelinating disease of the CNS, and in experimental autoimmune encephalomyelitis (EAE), a typical model of MS. We determined the levels of irisin in the serum and cerebrospinal fluid in patients with MS. The expression and histological distribution of irisin were determined in EAE. Serum irisin levels in patients with MS and in EAE mice were increased, and the levels of FNDC5/irisin mRNA were decreased in the spinal cord and brain regardless of the onset, peak or chronic phase of EAE. Immunofluorescence staining showed co-localization of irisin and neurones. The levels of irisin fluctuated with disease progression in MS and EAE. Irisin may be involved in the pathological process of MS/EAE.


Assuntos
Encefalomielite Autoimune Experimental , Fibronectinas , Regulação da Expressão Gênica , Esclerose Múltipla , Adulto , Animais , Encefalomielite Autoimune Experimental/líquido cefalorraquidiano , Encefalomielite Autoimune Experimental/imunologia , Feminino , Fibronectinas/líquido cefalorraquidiano , Fibronectinas/imunologia , Humanos , Masculino , Camundongos , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia
16.
Nat Commun ; 12(1): 3734, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145290

RESUMO

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.


Assuntos
Processamento Alternativo/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Células A549 , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromossomos Humanos Par 3/genética , Variações do Número de Cópias de DNA/genética , Fator de Transcrição E2F1/metabolismo , Células HCT116 , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Humanos , Células MCF-7 , Neoplasias/patologia , Correpressor 2 de Receptor Nuclear/genética , Interferência de RNA , RNA Interferente Pequeno/genética
17.
J Inflamm Res ; 14: 1575-1590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907438

RESUMO

Fibrosis is the final stage of the development of chronic inflammation. It is characterized by excessive deposition of the extracellular matrix, leading to tissue structure damage and organ dysfunction, which is a serious threat to human health and life. However, the molecular mechanism of fibrosis is still unclear. Inflammasome is a molecular complex of proteins that has been becoming a key innate sensor for host immunity and is involved in pyroptosis, pathogen infection, metabolic syndrome, cellular stress, and tumor metastasis. Inflammasome signaling and downstream cytokine responses mediated by the inflammasome have been found to play an important role in fibrosis. The inflammasome regulates the secretion of IL-1ß and IL-18, which are both critical for the process of fibrosis. Recently, researches on the function of inflammasome have attracted extensive attention, and data derived from these researches have increased our understanding of the effects and regulation of inflammasome during fibrosis. In this review, we emphasize the growing evidence for both indirect and direct effects of inflammasomes in triggering fibrosis as well as potential novel targets for antifibrotic therapies.

18.
Huan Jing Ke Xue ; 42(4): 2040-2046, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742839

RESUMO

In order to explore the effects of the exogenous addition of plant hormones on the antioxidant system and Cd absorption and accumulation of rice seedlings under Cd stress, the transportation and accumulation of Cd was reduced in plants to alleviate the stress of Cd on the rice. With the rice seedlings of Zhongjiazao 17 as the research object, a hydroponic experiment was carried out with three Cd concentration treatments (0, 5, and 25 µmol·L-1), and four exogenous plant hormone treatments:no plant hormones, 100 µmol·L-1 melatonin (MT), 0.2 µmol·L-1 2,4-epibrassinolide (EBL), and 0.2 µmol·L-1 jasmonic acid (JA), for a total of 12 treatments, each treatment repeated three times. The contents of Cd in the rice seedlings were analyzed, as well as the content of MDA, POD, CAT, and reduced GSH in the shoots and roots of the rice seedlings. The results indicated that under the stress of 5 µmol·L-1 and 25 µmol·L-1 Cd, the addition of MT, EBL, and JA significantly reduced the MDA content of the shoots by 11%-24%, and the roots and shoots were healthy. On the contrary, the addition of the three exogenous substances all caused an increase in the MDA content in the root system, but the effects of MT and EBL were obvious. Under the 5 µmol·L-1 Cd stress, compared with CK, the MDA contents increased by 45.5% and 20.0% respectively; under 25 µmol·L-1 Cd stress, they increased by 46.2% and 19.8%. The exogenous addition of plant hormones can significantly increase the activity of POD and CAT in the shoots and underground parts of the rice seedlings and reduce the contents of GSH and Cd. Under the 5 µmol·L-1 Cd stress, the Cd content in the shoots of rice plants decreased by 39.4%, 40.1%, and 51.6%, the roots were reduced by 38.9%, 40.2%, and 7.0%. Under the 25 µmol·L-1 Cd stress, the aboveground Cd content was reduced by 18.9%, 14.5%, and 35.6%, and the roots were reduced by 85.3%, 81.1%, and 56.5%. By exogenously adding low-concentration plant hormones MT, EBL, and JA, the stress of Cd on the rice can be alleviated, and the toxic effect of Cd on rice can be reduced.


Assuntos
Oryza , Plântula , Antioxidantes , Cádmio/toxicidade , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas
19.
Mult Scler Relat Disord ; 47: 102629, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33232908

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) may be similar to each other in clinical features. The differential diagnosis between them remains challenging in clinical practice. This retrospective study is aimed to describe the difference of cerebrospinal fluid (CSF) lactate level between aquaporin-4 antibody (AQP4-Ab) positive NMOSD and MS, to discuss the possible explanation upon immunopathogenesis and the significance in differential diagnosis. METHOD: We retrospectively analysed cerebral biochemical results from 60 AQP4-Ab positive NMOSD and 55 MS Asian patients. To assess the diagnostic ability of cerebrospinal fluid lactate for distinguishing AQP4-Ab positive NMOSD from MS using receiver operating characteristic (ROC) curve analysis. RESULTS: The cerebrospinal fluid lactate level is significantly higher in AQP4-Ab positive NMOSD than in MS based on multiple linear regression (P<0.0001). The differential diagnostic efficacy of cerebrospinal fluid lactate distinguishing AQP4-Ab positive NMOSD from MS reached an area under ROC curve (AUC) of 0.8842 (95% CI 0.82-0.95, P<0.0001), using 1.50 as the diagnostic critical point of the cerebrospinal fluid lactate level, the sensitivity was 88.3%, the specificity was 78.2%. CONCLUSION: The cerebrospinal fluid lactate level differs between AQP4-Ab positive NMOSD and MS, which also contributes in differential diagnosis. The distinct patterns of cerebral biochemical results may cast a light on the immunopathogenesis of AQP4-Ab positive NMOSD.


Assuntos
Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Diagnóstico Diferencial , Humanos , Lactatos , Neuromielite Óptica/diagnóstico , Estudos Retrospectivos
20.
Mult Scler Relat Disord ; 47: 102633, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33254090

RESUMO

BACKGROUND: Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS), and whether herpes simplex virus (HSV) infection is associated with the development of MS remains controversial. We aimed to investigate potential associations between MS or clinically isolated syndrome (CIS) and the prevalence of IgG and DNA for HSV in the clinical samples. METHODS: A systematic search of English databases (PubMed, Embase and Cochrane Library) was performed. The prevalence of IgG against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) and DNA for HSV-1 or HSV-2 in clinical samples were pooled and compared between patients with MS/CIS and controls using Stata 12.0. RESULTS: A total of 1756 patients with MS/CIS and 6429 controls from eight studies were included. The pooled results showed a significantly statistical difference in the seroprevalence of IgG against HSV-2 (OR 1.764, 95% CI [1.410 to 2.206], P = 0.000) between patients with MS/CIS and controls. However, no significantly statistical difference was shown in the seroprevalence of IgG against HSV-1 (OR 1.166, 95% CI [0.737 to 1.845], P = 0.512) between patients with MS/CIS and controls. Similarly, there was no significantly statistical difference in the prevalence of HSV-1 DNA (OR 0.957, 95% CI [0.310 to 2.949], P = 0.938) and HSV-2 DNA in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) (OR 0.506, 95% CI [0.022 to 11.416], P = 0.668) between patients with MS/CIS and controls. Subgroup analysis suggested that mean age at sampling might be a source of heterogeneity, and the seroprevalence of IgG against HSV-1 was significantly increased in the pediatric patients with MS/CIS (OR 1.488, 95% CI [1.130 to 1.959], P = 0.005), compared with the controls. CONCLUSIONS: The study demonstrated that prior HSV-1 infection might relate to the onset of pediatric MS/CIS and might not play a role in the development of adult MS. Furthermore, prior HSV-2 infection might have a correlation with MS/CIS. The mechanism remains to be further studied.


Assuntos
Herpes Simples , Esclerose Múltipla , Adulto , Anticorpos Antivirais , Criança , Herpes Simples/complicações , Herpes Simples/epidemiologia , Humanos , Imunoglobulina G , Leucócitos Mononucleares , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Estudos Soroepidemiológicos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...