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1.
J Org Chem ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780194

RESUMO

The Catellani reaction provides an efficient synthetic approach to polyfunctionalized arenes. However, the selective ortho-arylating reagents employed in these reactions have been strictly limited to activated bromoarenes. As demonstrated in this work, aryl diazonium salts bearing both electron-donating and electron-withdrawing substituents, after in situ transformations with KI into the corresponding iodoarenes, were efficient arylating reagents for Catellani type ortho-arylation approaches.

2.
J Nurs Manag ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34783114

RESUMO

AIM: To develop a patient experience with nursing care scale and to evaluate its psychometric properties. BACKGROUND: Patient experience is increasingly recognized as one of the pillars of quality in healthcare. Nevertheless, few instruments reflecting the preferences, needs and values of the healthcare recipients were developed to measure and improve patient experience with nursing care. METHODS: Instrument development and psychometric analysis were used, and a total of 1050 individuals participated in this study. The validity and reliability of the scale were evaluated. RESULTS: An exploratory factor analyses yielded a seven-dimension structure, and explained 70.785% of the variance. Confirmatory factor analyses supported the factor structure of the instrument. The content validity was very good (Mean I-CVI 0.96). Criterion validity was demonstrated with the general satisfaction question. Internal consistency reliability was found to be acceptable, as indicated by a Cronbach's alpha of 0.945, split-half reliability of 0.878 and item-total correlations of 0.328-0.803, respectively. CONCLUSIONS: This study produced a 30-item instrument, which exhibits good psychometric properties. IMPLICATIONS FOR NURSING MANAGEMENT: This scale could be used to determine to what extent patients' nursing care needs are met, examine the strength and weakness of current care delivery, and analyze the gap between patients' expectations and healthcare providers' behaviors.

3.
Int J Nurs Sci ; 8(4): 470-476, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34631997

RESUMO

Objectives: In recent years, the use of mobile health applications (mHealth apps) to deliver care for patients with breast cancer has increased exponentially. This study aimed to summarize the available evidence on developing mHealth apps to care for patients with breast cancer and identify the need for systematic efforts. Methods: A scoping review was performed according to Arksey and O'Malley's framework, aiming to identify eligible research studies in PubMed, CINAHL, and Web of Science between January 2010 and December 2020. All identified studies were screened, extracted, and analyzed independently by two reviewers. Results: A total of 676 studies were retrieved, and eight eligible studies were finally included. Four themes emerged: the involvement of patients and health professionals in the phases of design and development, patients' preferences, the characteristics of patients, and the motivators to use mHealth apps. The results indicated promising prospects for using mHealth apps to care for patients with breast cancer and identified the need for systematic efforts to develop and validate relevant apps. Conclusions: The attributes of patient characteristics, needs, and patient-reported outcomes data are vital components for developing mHealth apps for patients with breast cancer. Additionally, collaborative efforts, including patients, nurses, and other significant health professionals, should develop mHealth apps for breast cancer care. Additional research focusing on the design and development of mHealth apps for patients with breast cancer is warranted.

4.
Bioengineered ; 12(1): 8709-8723, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34711117

RESUMO

Long non-coding RNA (lncRNA)-microRNA-mRNA signaling axes have recently been shown to have a key role in the development of breast cancer (BC). In this study, we investigated how the cancer susceptibility candidate 9 (CASC9) gene affects the cell growth, invasion, migration, and apoptosis of BC cells. The levels of microRNA-590-3p (miR-590-3p), CASC9, and the sine oculis homeobox 1 (SIX1) gene were determined through qRT-PCR. We conducted cell counting kit-8 (CCK-8) assays to assess cell proliferation, transwell assays to detect cell migration/invasion, and flow cytometry to evaluate cell apoptosis. StarBase v2.0 was used to predict interactions between miR-590-3p and SIX1 or CASC9, and dual-luciferase reporter assays were used to verify these predictions. CASC9 protein was overexpressed in BC cells and tissues, while CASC9 knockdown inhibited BC cell growth, invasion, and migration and promoted apoptosis. Additionally, we verified that CASC9 competes for binding with miR-590-3p. Moreover, SIX1 was determined to be a target of miR-590-3p, and SIX1 expression was inhibited by miR-590-3p overexpression. CASC9 enhanced BC development by downregulating miR-590-3p and upregulating SIX1 during the activation of the NF-κB pathway. These data suggest that the CASC9/miR-590-3p/SIX1/NF-κB axis is involved in breast cancer progression, providing insight into the function of CASC9 in breast cancer development.

5.
ACS Appl Mater Interfaces ; 13(43): 51546-51555, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34689543

RESUMO

Sensors based on conductive hydrogels have received extensive attention in various fields, such as artificial intelligence, electronic skin, and health monitoring. However, the poor resilience and fatigue resistance, icing, and water loss of traditional hydrogels greatly limit their application. Herein, an ionic conductive organohydrogel (PAC-Zn) was prepared for the first time by copolymerization of cardanol and acrylic acid in water/1,3-butanediol as a binary solvent system. A very small amount of cardanol (1% cardanol of total monomers) could not only significantly improve the tensile strength (∼4 times) and toughness (∼3 times) of PAA but also improve its extensibility. Due to the presence of 1,3-butanediol, PAC-Zn showed outstanding tolerance for freezing (-45 °C) and drying (over 85% moisture retention after 15 days of storage in a 37 °C oven). Compared with ethylene glycol and glycerol as antifreeze agents used in organohydrogels, the addition of 1,3-butanediol endowed the organohydrogel with not only similar frost resistance but also better mechanical performance. Besides, PAC-Zn exhibited fast resilience (almost no hysteresis loop) and excellent antifatigue ability. More importantly, a PAC-Zn organohydrogel-based sensor could detect human motion in real time (wrist, elbow, finger, and knee joints), revealing its fast response, good sensitivity, and stable electromechanical repeatability. In conclusion, the multifunctional PAC-Zn organohydrogel is expected to become a potential and promising candidate in the field of strain sensors under a broad range of environmental temperatures.

6.
Org Lett ; 23(21): 8317-8321, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34633187

RESUMO

An efficient photopromoted dehydroxylative ring-expansion approach to eight-membered benzolactams that employ phthalocyanine iron(II) as the photosensitizer has been developed. This cascade reaction protocol, featuring a visible-light-promoted dehydroxylative amination and oxidative ring-expansion lactamization of 4-hydroxyphenols with N-alkyl-4-piperidinones, provides a green and reliable approach to a diverse array of valuable eight-membered benzolactams with high chemo- and regioselectivity.

8.
Entropy (Basel) ; 23(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34356434

RESUMO

Finding the critical factor and possible "Newton's laws" in financial markets has been an important issue. However, with the development of information and communication technologies, financial models are becoming more realistic but complex, contradicting the objective law "Greatest truths are the simplest." Therefore, this paper presents an evolutionary model independent of micro features and attempts to discover the most critical factor. In the model, information is the only critical factor, and stock price is the emergence of collective behavior. The statistical properties of the model are significantly similar to the real market. It also explains the correlations of stocks within an industry, which provides a new idea for studying critical factors and core structures in the financial markets.

9.
Int J Biol Macromol ; 189: 857-868, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464642

RESUMO

Hirsutella sinensis, the anamorph of Ophiocordyceps sinensis (syn. Cordyceps sinensis), is a great substitute for precious and rare wild Cordyceps sinensis to effectively treat a variety of lung and kidney diseases. In this study, an α-glucan (named as HSWP-2a) was obtained by hot water extraction, DEAE-cellulose separation, and Sepharose CL-6B purification from H. sinensis mycelia. Different from known α-glucans, HSWP-2a is an α-(1 â†’ 4)-D-glucan that branched at O-6, O-3, or O-2 with a terminal 1-linked α-D-Glcp as side chain, with an average molecular weight of 870.70 kDa. Immunological tests showed that HSWP-2a could remarkably enhance the phagocytosis of macrophages and increase the production of NO, IL-1ß, IL-6, and TNF-α, via activating the p38, JNK, and NF-κB signaling pathways. Moreover, HSWP-2a could significantly promote splenic lymphocyte proliferation. Taken together, HSWP-2a may be potentially utilized as a natural immunomodulatory agent.

10.
EMBO J ; 40(19): e108482, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34459010

RESUMO

Sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) 2b is a ubiquitous SERCA family member that conducts Ca2+ uptake from the cytosol to the ER. Herein, we present a 3.3 Å resolution cryo-electron microscopy (cryo-EM) structure of human SERCA2b in the E1·2Ca2+ state, revealing a new conformation for Ca2+ -bound SERCA2b with a much closer arrangement of cytosolic domains than in the previously reported crystal structure of Ca2+ -bound SERCA1a. Multiple conformations generated by 3D classification of cryo-EM maps reflect the intrinsically dynamic nature of the cytosolic domains in this state. Notably, ATP binding residues of SERCA2b in the E1·2Ca2+ state are located at similar positions to those in the E1·2Ca2+ -ATP state; hence, the cryo-EM structure likely represents a preformed state immediately prior to ATP binding. Consistently, a SERCA2b mutant with an interdomain disulfide bridge that locks the closed cytosolic domain arrangement displayed significant autophosphorylation activity in the presence of Ca2+ . We propose a novel mechanism of ATP binding to SERCA2b.

11.
PLoS Biol ; 19(8): e3001304, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34437534

RESUMO

Tumor necrosis factor receptor-1 (TNFR1) signaling, apart from its pleiotropic functions in inflammation, plays a role in embryogenesis as deficiency of varieties of its downstream molecules leads to embryonic lethality in mice. Caspase-8 noncleavable receptor interacting serine/threonine kinase 1 (RIPK1) mutations occur naturally in humans, and the corresponding D325A mutation in murine RIPK1 leads to death at early midgestation. It is known that both the demise of Ripk1D325A/D325A embryos and the death of Casp8-/- mice are initiated by TNFR1, but they are mediated by apoptosis and necroptosis, respectively. Here, we show that the defects in Ripk1D325A/D325A embryos occur at embryonic day 10.5 (E10.5), earlier than that caused by Casp8 knockout. By analyzing a series of genetically mutated mice, we elucidated a mechanism that leads to the lethality of Ripk1D325A/D325A embryos and compared it with that underlies Casp8 deletion-mediated lethality. We revealed that the apoptosis in Ripk1D325A/D325A embryos requires a scaffold function of RIPK3 and enzymatically active caspase-8. Unexpectedly, caspase-1 and caspase-11 are downstream of activated caspase-8, and concurrent depletion of Casp1 and Casp11 postpones the E10.5 lethality to embryonic day 13.5 (E13.5). Moreover, caspase-3 is an executioner of apoptosis at E10.5 in Ripk1D325A/D325A mice as its deletion extends life of Ripk1D325A/D325A mice to embryonic day 11.5 (E11.5). Hence, an unexpected death pathway of TNFR1 controls RIPK1 D325A mutation-induced lethality at E10.5.


Assuntos
Caspase 8/fisiologia , Desenvolvimento Embrionário , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Animais , Caspases/metabolismo , Morte Celular , Camundongos , Cultura Primária de Células , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
12.
BMC Pediatr ; 21(1): 317, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271894

RESUMO

BACKGROUND: Biliary atresia (BA) is a severe cholangiopathy possibly resulting from virus-induced and immune-mediated injury of the biliary system. IFN-γ, secreted from CD4+ Th1 cells and CD8+ cytotoxic T cells, is a major mediator of liver pathology. Programmed death protein-1 (PD-1) signaling suppresses T cell function. However, how PD-1 modify T cell function in BA remains incompletely understood. METHODS: Frequencies of PD-1 expressing CD4+ and CD8+ T cells were analyzed in the liver and blood from BA and control subjects. Associations of PD-1+CD4+/CD8+T cell abundances with liver function indices were measured. Function of PD-1 was measured by administration of an anti-PD-1 antibody in a Rhesus Rotavirus (RRV)-induced BA model. Survival, histology, direct bilirubin, liver immune cell subsets and cytokine production were analyzed. RESULTS: PD-1 was significantly upregulated in CD4+ and CD8+ T cells in patients with BA compared with control subjects. PD-1 expression in T cells was negatively associated with IFN-γ concentration in liver (PD-1+CD4+T cells in liver vs. IFN-γ concentration, r = - 0.25, p = 0.05; PD-1+CD8+T cells in liver vs. IFN-γ concentration, r = - 0.39, p = 0.004). Blockade of PD-1 increased IFN-γ expression in CD4+ T and CD8+ T cells (RRV vs. anti-PD-1 treated RRV mice: 11.59 ± 3.43% vs. 21.26 ± 5.32% IFN-γ+ in hepatic CD4+T cells, p = 0.0003; 9.33 ± 4.03% vs. 22.55 ± 7.47% IFN-γ+ in hepatic CD8+T cells, p = 0.0001), suppressed bilirubin production (RRV vs. anti-PD-1 treated RRV mice: 285.4 ± 47.93 vs. 229.8 ± 45.86 µmol/L total bilirubin, p = 0.01) and exacerbated liver immunopathology. CONCLUSIONS: PD-1 plays a protective role in infants with BA by suppressing IFN-γ production in T cells. Increasing PD-1 signaling may serve as a therapeutic strategy for BA.


Assuntos
Linfócitos T CD8-Positivos , Interferon gama/imunologia , Receptor de Morte Celular Programada 1 , Animais , Animais Recém-Nascidos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Humanos , Lactente , Fígado , Camundongos , Camundongos Endogâmicos BALB C
13.
Bioelectromagnetics ; 42(7): 593-602, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289513

RESUMO

We previously found that a near-null magnetic field affected reproductive growth in Arabidopsis under white light. To test whether the effect of a near-null magnetic field on fruit growth of Arabidopsis is related to cryptochrome, we grew wild-type Arabidopsis and cryptochrome double mutant, cry1/cry2, in a near-null magnetic field under blue light. We found that fruit growth of wild-type Arabidopsis instead of the cry1/cry2 mutant was suppressed by the near-null magnetic field. Furthermore, gibberellin (GA) levels of GA4 , GA9 , GA34 , and GA51 in fruits of wild-type plants in the near-null magnetic fields were significantly lower than local geomagnetic field controls. However, in cry1/cry2 mutants, levels of the four detected GAs in fruits in the near-null magnetic fields did not differ significantly from controls. Expressions of GA20-oxidase (GA20ox) genes (GA20ox1 and GA20ox2) and GA3-oxidase (GA3ox) genes (GA3ox1 and GA3ox3) in fruits of wild-type plants rather than cry1/cry2 mutants were downregulated by the near-null magnetic field. In contrast, expressions of GA2-oxidase (GA2ox) genes and GA signaling genes were not affected by the near-null magnetic field. These results indicate that suppression of fruit growth by the near-null magnetic field is mediated by cryptochrome and that GAs are involved in the regulation of fruit growth by the near-null magnetic field. © 2021 Bioelectromagnetics Society.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Criptocromos/genética , Criptocromos/metabolismo , Frutas , Regulação da Expressão Gênica de Plantas , Luz , Campos Magnéticos
14.
Sci Adv ; 7(26)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34162535

RESUMO

Mutation of ciliopathy protein HYLS1 causes the perinatal lethal hydrolethalus syndrome (HLS), yet the underlying molecular etiology and pathogenesis remain elusive. Here, we reveal unexpected mechanistic insights into the role of mammalian HYLS1 in regulating primary cilia. HYLS1 is recruited to the ciliary base via a direct interaction with the type Iγ phosphatidylinositol 4-phosphate [PI(4)P] 5-kinase (PIPKIγ). HYLS1 activates PIPKIγ by interrupting the autoinhibitory dimerization of PIPKIγ, which thereby expedites depletion of centrosomal PI(4)P to allow axoneme nucleation. HYLS1 deficiency interrupts the assembly of ciliary NPHP module and agonist-induced ciliary exit of ß-arrestin, which, in turn, disturbs the removal of ciliary Gpr161 and activation of hedgehog (Hh) signaling. Consistent with this model of pathogenesis, the HLS mutant HYLS1D211G supports ciliogenesis but not activation of Hh signaling. These results implicate mammalian HYLS1 as a multitasking protein that facilitates ciliogenesis and ciliary signaling by coordinating with the ciliary lipid kinase PIPKIγ.

15.
Front Plant Sci ; 12: 685189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178005

RESUMO

The remodeling of transcriptome, epigenome, proteome, and metabolome in hybrids plays an important role in heterosis. N(6)-methyladenosine (m6A) methylation is the most abundant type of post-transcriptional modification for mRNAs, but the pattern of inheritance from parents to hybrids and potential impact on heterosis are largely unknown. We constructed transcriptome-wide mRNA m6A methylation maps of Arabidopsis thaliana Col-0 and Landsberg erecta (Ler) and their reciprocal F1 hybrids. Generally, the transcriptome-wide pattern of m6A methylation tends to be conserved between accessions. Approximately 74% of m6A methylation peaks are consistent between the parents and hybrids, indicating that a majority of the m6A methylation is maintained after hybridization. We found a significant association between differential expression and differential m6A modification, and between non-additive expression and non-additive methylation on the same gene. The overall RNA m6A level between Col-0 and Ler is clearly different but tended to disappear at the allelic sites in the hybrids. Interestingly, many enriched biological functions of genes with differential m6A modification between parents and hybrids are also conserved, including many heterosis-related genes involved in biosynthetic processes of starch. Collectively, our study revealed the overall pattern of inheritance of mRNA m6A modifications from parents to hybrids and a potential new layer of regulatory mechanisms related to heterosis formation.

16.
Oncol Lett ; 22(1): 544, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34084220

RESUMO

Previous studies have shown that lutein can inhibit the proliferation of breast cancer cells. However, the mechanism of lutein inhibiting the proliferation of breast cancer cells remains unclear. The present study aimed to determine whether the long non-coding RNA (lncRNA) Cancer Susceptibility 9 (CASC9)/microRNA (miR)-590-3p axis participates in the antiproliferative effects of lutein via lncRNA microarray hybridization, reverse transcription-quantitative PCR, dual-luciferase reporter and MTT assays. The results demonstrated that CASC9 was the most significantly downregulated lncRNA in MCF7 cells treated with lutein. miR-590-3p was identified as the target of CASC9. In addition, lutein downregulated CASC9 expression and upregulated miR-590-3p expression in dose- and time-dependent manners, respectively. CASC9 knockdown or overexpression of miR-590-3p inhibited the proliferation of breast cancer cells. Notably, simultaneous transfection with miR-590-3p mimics and CASC9 small interfering RNA increased the potency of lutein in inhibiting the proliferation of breast cancer cells. Taken together, these results suggest that the CASC9/miR-590-3p axis participates in the antiproliferative effects of lutein on breast cancer.

17.
PLoS Genet ; 17(6): e1009618, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34115759

RESUMO

Coordination of neurite extension with surrounding glia development is critical for neuronal function, but the underlying molecular mechanisms remain poorly understood. Through a genome-wide mutagenesis screen in C. elegans, we identified dyf-4 and daf-6 as two mutants sharing similar defects in dendrite extension. DAF-6 encodes a glia-specific patched-related membrane protein that plays vital roles in glial morphogenesis. We cloned dyf-4 and found that DYF-4 encodes a glia-secreted protein. Further investigations revealed that DYF-4 interacts with DAF-6 and functions in a same pathway as DAF-6 to regulate sensory compartment formation. Furthermore, we demonstrated that reported glial suppressors of daf-6 could also restore dendrite elongation and ciliogenesis in both dyf-4 and daf-6 mutants. Collectively, our data reveal that DYF-4 is a regulator for DAF-6 which promotes the proper formation of the glial channel and indirectly affects neurite extension and ciliogenesis.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Genoma Helmíntico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Neurogênese/genética , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Comunicação Celular , Cílios/genética , Cílios/metabolismo , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutagênese , Proteínas do Tecido Nervoso/metabolismo , Neuritos/metabolismo , Neuroglia/citologia , Neuroglia/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
18.
Cell Prolif ; 54(6): e13018, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33945189

RESUMO

BACKGROUND: Endothelial-to-mesenchymal transition (EndMT) is a common pathophysiology in valvular calcification (VC) among non-chronic kidney disease (CKD) patients. However, few studies were investigated in CKD-induced VC. Parathyroid hormone (PTH) was considered to be an important component of EndMT in CKD-induced cardiovascular diseases. Therefore, determining whether PTH could induce valvular EndMT and elucidating corresponding mechanism involved further study. METHODS: Performing a 5/6 nephrectomy with a high phosphorus diet was done to construct VC models in rats with CKD. miRNA sequencing was used to ascertain changes in microRNA in human umbilical vein endothelial cells (HUVECs) intervened by PTH. VC was observed by Von Kossa staining and scanning electron microscope. RESULTS: PTH induced valvular EndMT in VC. Global microRNA expression profiling of HUVECs was examined in PTH versus the control in vitro, in which miR-29a-5p was most notably decreased and was resumed by PTHrP(7-34) (PTH-receptor1 inhibitor). Overexpression of miR-29a-5p could inhibit PTH-induced EndMT in vitro and valvular EndMT in vivo. The dual-luciferase assay verified that γ-secretase-activating protein (GASP) served as the target of miR-29a-5p. miR-29a-5p-mimics, si-GSAP and DAPT (γ-secretase inhibitor) inhibited PTH-induced γ-secretase activation, thus blocking Notch1 pathway activation to inhibit EndMT in vitro. Moreover, Notch1 pathway activation was observed in VC. Blocking Notch1 pathway activation via AAV-miR-29a and DAPT inhibited valvular EndMT. In addition, blocking Notch1 pathway activation was also shown to alleviate VC. CONCLUSION: PTH activates valvular EndMT via miR-29a-5p/GSAP/Notch1 pathway, which can contribute to VC in CKD rats.


Assuntos
Estenose da Valva Aórtica/etiologia , Valva Aórtica/patologia , Calcinose/etiologia , MicroRNAs/genética , Hormônio Paratireóideo/metabolismo , Receptor Notch1/metabolismo , Insuficiência Renal Crônica/complicações , Animais , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Calcinose/genética , Calcinose/metabolismo , Calcinose/patologia , Endotélio/metabolismo , Endotélio/patologia , Transição Epitelial-Mesenquimal , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , MicroRNAs/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Notch1/genética , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Transdução de Sinais , Transcriptoma , Regulação para Cima
19.
Front Oncol ; 11: 691199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055653

RESUMO

Background: Liver cancer is a leading cause of cancer death worldwide, and novel prognostic factor is needed for early detection and therapeutic responsiveness monitoring. The orphan nuclear receptor NR0B2 was reported to suppress liver cancer development in a mouse model, and its expression levels were reduced in liver cancer tissues and cell lines due to hypermethylation within its promoter region. However, it is not clear if NR0B2 expression is associated with cancer survival or disease progression and how NR0B2 gene expression is regulated at the molecular level. Methods: Multiple cancer databases were utilized to explore NR0B2 gene expression profiles crossing a variety of human cancers, including liver cancers, on several publicly assessable bioinformatics platforms. NR0B2 gene expression with or without kinase inhibitor treatment was analyzed using the qPCR technique, and NR0B2 protein expression was assessed in western blot assays. Two human hepatocellular carcinoma cell lines HepG2 and Huh7, were used in these experiments. NR0B2 gene activation was evaluated using NR0B2 promoter-driven luciferase reporter assays. Results: NR0B2 gene is predominantly expressed in liver tissue crossing human major organs or tissues, but it is significantly downregulated in liver cancers. NR0B2 expression is mostly downregulated in most common cancers but also upregulated in a few intestinal cancers. NR0B2 gene expression significantly correlated with patient overall survival status in multiple human malignancies, including lung, kidney, breast, urinary bladder, thyroid, colon, and head-neck cancers, as well as liposarcoma and B-cell lymphoma. In liver cancer patients, higher NR0B2 expression is associated with favorite relapse-free and progression-free survival, especially in Asian male patients with viral infection history. In addition, NR0B2 expression negatively correlated with immune infiltration and PIK3CA and PIK3CG gene expression in liver cancer tissues. In HepG2 and Huh7 cells, NR0B2 expression at the transcription level was drastically reduced after MAPK inhibition but was significantly enhanced after PI3K inhibition. Conclusion: NR0B2 gene expression is altered mainly in most human malignancies and significantly reduced in liver cancers. NR0B2 is a prognosis factor for patient survival in liver cancers. MAPK and PI3K oppositely modulate NR0B2 expression, and NR0B2 gene upregulation might serve as a therapeutic responsiveness factor in anti-PI3K therapy for liver cancer.

20.
Int J Clin Pract ; 75(8): e14273, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33908133

RESUMO

AIMS: Stevens-Johnson syndrome and toxic epidermal necrolysis are viewed as the most severe drug-induced types of cutaneous adverse reactions, with high rates of morbidity and mortality. We aimed to examine carbamazepine- and oxcarbazepine-associated Stevens-Johnson syndrome or toxic epidermal necrolysis, by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Reports in FAERs were analysed, from the first quarter of 2004 to the last quarter of 2019. Pharmacovigilance tools were employed for the quantitative detection of signals, where a signal represents a drug-associated adverse event, including the reporting odds ratio, proportional reporting ratio, an information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. RESULTS: The total number of reports identified as Stevens-Johnson syndrome or toxic epidermal necrolysis associated with carbamazepine or oxcarbazepine included in this study was 1231. FAERS reports associated with carbamazepine were 1048, including Stevens-Johnson syndrome (n = 668) and toxic epidermal necrolysis(n = 380). FAERS reports associated with oxcarbazepine were 183, including 142 Stevens-Johnson syndrome and 41 toxic epidermal necrolysis reports. The risk for Stevens-Johnson syndrome is higher than for toxic epidermal necrolysis and carbamazepine is associated with a higher risk than oxcarbazepine. CONCLUSIONS: The results of our study are consistent with clinical observations, suggesting the necessity for further clinical research on Stevens-Johnson syndrome and toxic epidermal necrolysis associated with carbamazepine or oxcarbazepine.


Assuntos
Síndrome de Stevens-Johnson , Teorema de Bayes , Carbamazepina/efeitos adversos , Mineração de Dados , Humanos , Oxcarbazepina , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
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