Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Front Aging ; 4: 1126172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37229241

RESUMO

Objective: This study aimed to identify factors significantly associated with the occurrence of osteoporosis in elderly and very elderly patients. Methods: Elderly hospitalized patients who were older than 60 years old, from the Rehabilitation Hospital from December 2019 to December 2020 were selected. Barthel index (BI), nutritional assessment, the causes of bone mineral density (BMD) reductions in elderly and elderly patients were analysed. Results: A total of 94 patients (83.56 ± 8.37 years old) were enrolled. With increasing age, the BMD of the lumbar spine, femoral neck, and femoral shaft of elderly patients significantly decreased, and the incidence of osteoporosis (OP) significantly increased. The BMD of the lumbar spine was negatively correlated with female and positively correlated with serum 25-hydroxyvitamin D levels, the difference between actual body weight and ideal body weight, and blood uric acid levels; The BMD of the femoral neck was negatively correlated with age and female, and positively correlated with height and geriatric nutrition risk index score. The BMD of the femoral shaft was negatively correlated with female and positively correlated with BI. Conclusion: With increasing age, the BMD of the lumbar spine and the femoral shaft significantly decreased, and the incidence of OP significantly increased in elderly and very elderly patients. Aric acid may protect bone health in elderly patients. Early attention to the nutritional status, exercise capacity, 25-hydroxyvitamin D level, and blood uric acid level in the elderly population can help identify high-risk elderly patients with OP.

2.
iScience ; 26(4): 106461, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37091246

RESUMO

Memristors are promising information storage devices for commercial applications because of their long endurance and low power consumption. Particularly, perovskite memristors have revealed excellent resistive switching (RS) properties owing to the fast ion migration and solution fabrication process. Here, an n-i-p type double perovskite memristor with "ITO/SnO2/Cs2AgBiBr6/NiOx/Ag" architecture was developed and demonstrated to reveal three resistance states because of the p-n junction electric field coupled with ion migration. The devices exhibited reliable filamentary with an on/off ratio exceeding 50. The RS characteristics remained unchanged after 1000 s read and 300 switching cycles. The synaptic functions were examined through long-term depression and potentiation measurements. Significantly, the device still worked after one year to reveal long-term stability because of the all-inorganic layers. This work indicates a novel idea for designing a multistate memristor by utilizing the p-n junction unidirectional conductivity during the forward and reverse scanning.

3.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1310-1318, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-37005815

RESUMO

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.


Assuntos
Insuficiência Ovariana Primária , Feminino , Humanos , Camundongos , Animais , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente , Proteômica , Transdução de Sinais , Glicosídeos/efeitos adversos
4.
Plant Cell ; 35(6): 1848-1867, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-36905284

RESUMO

The dynamics of gene expression in crop grains has typically been investigated at the transcriptional level. However, this approach neglects translational regulation, a widespread mechanism that rapidly modulates gene expression to increase the plasticity of organisms. Here, we performed ribosome profiling and polysome profiling to obtain a comprehensive translatome data set of developing bread wheat (Triticum aestivum) grains. We further investigated the genome-wide translational dynamics during grain development, revealing that the translation of many functional genes is modulated in a stage-specific manner. The unbalanced translation between subgenomes is pervasive, which increases the expression flexibility of allohexaploid wheat. In addition, we uncovered widespread previously unannotated translation events, including upstream open reading frames (uORFs), downstream open reading frames (dORFs), and open reading frames (ORFs) in long noncoding RNAs, and characterized the temporal expression dynamics of small ORFs. We demonstrated that uORFs act as cis-regulatory elements that can repress or even enhance the translation of mRNAs. Gene translation may be combinatorially modulated by uORFs, dORFs, and microRNAs. In summary, our study presents a translatomic resource that provides a comprehensive and detailed overview of the translational regulation in developing bread wheat grains. This resource will facilitate future crop improvements for optimal yield and quality.


Assuntos
MicroRNAs , Triticum , Triticum/genética , Pão , MicroRNAs/genética , RNA Mensageiro , Polirribossomos , Fases de Leitura Aberta/genética , Grão Comestível/genética , Biossíntese de Proteínas/genética
5.
Plant Sci ; 331: 111676, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36933836

RESUMO

Heat stress is a limiting factor in wheat production along with global warming. Development of heat-tolerant wheat varieties and generation of suitable pre-breeding materials are the major goals in current wheat breeding programs. Our understanding on the genetic basis of thermotolerance remains sparse. In this study, we genotyped a collection of 211 core spring wheat accessions and conducted field trials to evaluate the grain-related traits under heat stress and non-stress conditions in two different locations for three consecutive years. Based on SNP datasets and grain-related traits, we performed genome-wide association study (GWAS) to detect stable loci related to thermotolerance. Thirty-three quantitative trait loci (QTL) were identified, nine of them are the same loci as previous studies, and 24 are potentially novel loci. Functional candidate genes at these QTL are predicted and proved to be relevant to heat stress and grain-related traits such as TaELF3-A1 (1A) for earliness per se (Eps), TaHSFA1-B1 (5B) influencing heat tolerance and TaVIN2-A1 (6A) for grain size. Functional markers of TaELF3-A1 were detected and converted to KASP markers, with their function and genetic diversity being analyzed in the natural populations. In addition, our results unveiled favor alleles controlling agronomic traits and/or heat stress tolerance. In summary, we provide insights into heritable correlation between yield and heat stress tolerance, which will accelerate the development of new cultivars with high and stable yield of wheat in the future.


Assuntos
Termotolerância , Triticum , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Fenótipo , Grão Comestível/genética , Termotolerância/genética , Polimorfismo de Nucleotídeo Único/genética
6.
Acta Cardiol ; 78(1): 135-141, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35899777

RESUMO

BACKGROUND: The intracoronary provocation test is expensive and may cause complications. Therefore, we investigated the sensitivity, specificity and safety of different drug- and dose-peripheral artery provocation tests in the diagnosis of coronary artery spasm (CAS). METHODS: The patients who had repeated chest pain as well as both coronary and radial stenoses <50% were selected. These patients were divided into CAS group (n = 24) and control group (n = 33) after the intracoronary ergonovine provocation test. All patients underwent radial artery provocation tests at different dose-acetylcholine (200 µg, 400 µg and 800 µg) and ergonovine (60 µg, 100 µg and 160 µg). The predictive values of radial provocation tests for CAS diagnosis were analysed using receiver operator characteristic (ROC) curves. RESULTS: In radial acetylcholine provocation tests, 200 µg of acetylcholine failed to induce radial artery spasm, and the radial artery stenosis degree was not significantly different between the CAS group and control group at 400 µg and 800 µg of acetylcholine (all p > 0.05). In the radial artery ergonovine provocation tests, the radial artery stenosis degree was all significantly higher in the CAS group than in the control group at the three different doses (all p < 0.05). The specificity and sensitivity of radial ergonovine provocation tests were 90.91% and 50.00% at 60 µg, 96.97% and 66.67% at 100 µg, and 90.91% and 95.83% at 160 µg. Only the radial 160 µg-ergonovine provocation test caused CAS in one case. CONCLUSION: The radial acetylcholine provocation test has no diagnostic value for CAS. The radial 160 µg-ergonovine provocation test has higher sensitivity and specificity for CAS diagnosis, but its safety should be paid attention to.


Assuntos
Vasoespasmo Coronário , Humanos , Vasoespasmo Coronário/induzido quimicamente , Vasoespasmo Coronário/diagnóstico , Ergonovina/efeitos adversos , Acetilcolina , Artéria Radial , Constrição Patológica , Angiografia Coronária , Espasmo , Vasos Coronários
7.
J Environ Sci (China) ; 124: 310-318, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182141

RESUMO

BiFeO3 (BFO), as a kind of narrow band-gap semiconductor material, has gradually emerged advantages in the application of photocatalysis. In this paper, Ca doped BFO nanoparticles Bi0.9Ca0.1FeO3 (BCFO) were prepared by sol-gel method. And BCFO and CdS nanocomposites with two morphologies were obtained by controlling the time of loading CdS under a low temperature liquid phase process. It is found that the band gap becomes narrower after doping Ca into BFO, which is conducive to the absorption of visible light. Among all the samples, the composite of CdS nanowires and BCFO nanoparticles obtained by reaction time of 10 min has the best photocatalytic performance. The degradation rate of Methyl Orange solution was 94% after 90 min under visible light irradiation, which was much higher than that of pure BCFO and CdS. Furthermore, significant enhancement in the degradation rate (100% degradation in 60 min) can be achieved in poled samples after electric polarization process. The highest degradation rate is due to the promoted separation of photogenerated carriers induced by the internal polarization field and the formation of S-scheme heterostructure between BCFO and CdS. Such BCFO-CdS nanocomposites may bring new insights into designing highly efficient photocatalyst.

8.
J Med Chem ; 65(24): 16716-16740, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36512734

RESUMO

Janus kinase 1 (JAK1) is a potential target for the treatment of rheumatoid arthritis (RA). In this study, the introduction of a spiro ring with a difluoro-substituted cyclopropionamide resulted in the identification of TUL01101 (compound 36) based on a triazolo[1,5-a]pyridine core of filgotinib. It showed excellent potency on JAK1 with an IC50 value of 3 nM and exhibited more than 12-fold selectivity for JAK2 and TYK2. Whole blood assay also demonstrated the high activity and selectivity (37-fold for JAK2). At the same time, TUL01101 also demonstrated excellent metabolic stability and pharmacokinetics (PK) profiles were assayed in three species (mouse, rat, and dog). Moreover, it has been validated for effective activity in the treatment of RA both in collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models, with low dose and low toxicity. Now, TUL01101 has progressed into phase I clinical trials.


Assuntos
Artrite Experimental , Artrite Reumatoide , Janus Quinase 1 , Inibidores de Janus Quinases , Animais , Cães , Camundongos , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Bioensaio , Janus Quinase 1/antagonistas & inibidores , Inibidores de Janus Quinases/farmacocinética , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico
9.
Anal Methods ; 15(1): 99-108, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36484245

RESUMO

Aflatoxin B1 (AFB1) is a highly toxic mycotoxin, which causes severe acute or cumulative poisoning. Therefore, it is important to develop sensitive and selective detection methods for AFB1 for the safety of food and medicinal herbs. Herein, we have developed a "signal-on" electrochemical aptasensor based on the high specificity of the aptamer and hybridization chain reaction (HCR) biological amplification for AFB1 detection. In this work, thiol-modified complementary DNA (cDNA) immobilized on the surface of a gold electrode (GE) served as an initiator DNA. When AFB1 was present, it competed with the cDNA for binding to the aptamers, which resulted in the detaching of aptamers from the cDNA-aptamer duplexes. Then, the single-stranded cDNA acted as an initiator to trigger the HCR signal amplification. Therefore, long double-stranded DNA (dsDNA) products were produced, which could load large amounts of methylene blue (MB) molecules to generate a distinct electrochemical signal. Under the optimized conditions, the proposed electrochemical aptasensor achieved the ultrasensitive detection of AFB1 with a linear detection range of 0.01-100 pg mL-1, and a limit of detection (LOD) down to 2.84 fg mL-1. Furthermore, the electrochemical aptasensor was successfully applied for detecting AFB1 in corn and two kinds of traditional Chinese medicine samples, indicating the potential value for AFB1 detection in practical samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA Complementar/química , Aflatoxina B1/análise , Aflatoxina B1/química , Aptâmeros de Nucleotídeos/química , Contaminação de Alimentos/análise , Técnicas Eletroquímicas/métodos , DNA/química , Técnicas Biossensoriais/métodos
10.
Small ; 18(47): e2204557, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36216775

RESUMO

Defect engineering of transition metal dichalcogenides (TMDCs) is important for improving electrocatalytic hydrogen evolution reaction (HER) performance. Herein, a facile and scalable atomic-level di-defect strategy over thermodynamically stable VSe2 nanoflakes, yielding attractive improvements in the electrocatalytic HER performance over a wide electrolyte pH range is reported. The di-defect configuration with controllable spatial relation between single-atom (SA) V defects and single Se vacancy defects effectively triggers the electrocatalytic HER activity of the inert VSe2 basal plane. When employed as a cathode, this di-defects decorated VSe2 electrocatalyst requires overpotentials of 67.2, 72.3, and 122.3 mV to reach a HER current density of 10 mA cm-2 under acidic, alkaline, and neutral conditions, respectively, which are superior to most previously reported non-noble metal HER electrocatalysts. Theoretical calculations reveal that the reactive microenvironment consists of two adjacent SA Mo atoms with two surrounding symmetric Se vacancies, yielding optimal water dissociation and hydrogen desorption kinetics. This study provides a scalable strategy for improving the electrocatalytic activity of other TMDCs with inert atoms in the basal plane.

11.
Front Immunol ; 13: 945129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979373

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease involving joints, with clinical manifestations of joint inflammation, bone damage and cartilage destruction, joint dysfunction and deformity, and extra-articular organ damage. As an important source of new drug molecules, natural medicines have many advantages, such as a wide range of biological effects and small toxic and side effects. They have become a hot spot for the vast number of researchers to study various diseases and develop therapeutic drugs. In recent years, the research of natural medicines in the treatment of RA has made remarkable achievements. These natural medicines mainly include flavonoids, polyphenols, alkaloids, glycosides and terpenes. Among them, resveratrol, icariin, epigallocatechin-3-gallate, ginsenoside, sinomenine, paeoniflorin, triptolide and paeoniflorin are star natural medicines for the treatment of RA. Its mechanism of treating RA mainly involves these aspects: anti-inflammation, anti-oxidation, immune regulation, pro-apoptosis, inhibition of angiogenesis, inhibition of osteoclastogenesis, inhibition of fibroblast-like synovial cell proliferation, migration and invasion. This review summarizes natural medicines with potential therapeutic effects on RA and briefly discusses their mechanisms of action against RA.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Fibroblastos , Humanos , Polifenóis/farmacologia
12.
Bioorg Med Chem Lett ; 74: 128905, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35870730

RESUMO

Selective inhibition of JAK kinases within the JAK family has been a desired goal of research in order to maximize efficacy while reducing undesired off target effect. Aiming to minimize adverse effects such as anemia, a promising new class of pyrrolo[2,3-d]pyrimidine series containing a hydrazinyl moiety were synthesized and profiled. Among them compound 8m and 8o showed the best enzymatic activity against JAK1 with IC50 value of 0.16 nM and 0.3 nM respectively, and with selectivity over JAK2 by 40.6 and 10 folds respectively. In addition, 8o had an improved PK profile and demonstrated better in vivo efficacy than Tofacitinib in CIA model.


Assuntos
Artrite Reumatoide , Inibidores de Janus Quinases , Pirimidinas , Artrite Reumatoide/tratamento farmacológico , Humanos , Janus Quinase 1 , Inibidores de Janus Quinases/farmacologia , Pirimidinas/farmacologia
13.
Lab Med ; 53(5): 500-503, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35639810

RESUMO

OBJECTIVE: The purpose of this study was to investigate whether local application of methyl nicotinate solution can change the content and proportion of blood cells in peripheral blood samples and to determine whether this treatment is a safe and reliable method for improving peripheral blood collection. METHODS: Routine blood analysis and flow cytometry were used to analyze the contents and proportions of blood cells and T lymphocyte subsets in peripheral blood samples. Experimental blood specimens were collected from earlobes treated with different concentrations of methyl nicotinate solution, and the control group consisted of blood specimens collected from untreated earlobes. RESULTS: The blood flow in the earlobe was significantly increased after methyl nicotinate solution stimulation, especially when the methyl nicotinate solution concentration was greater than 10-4 mol/L. There were no significant changes in the proportions of white blood cells, red blood cells, platelets, neutrophils, eosinophils, basophils, monocytes, or lymphocytes in the peripheral blood obtained from earlobes treated with methyl nicotinate solution. The proportion of T lymphocytes increased in the experimental group, but this difference was not significant. CONCLUSION: Local application of methyl nicotinate solution is a feasible method for improving peripheral blood collection, especially for patients with venous blood collection phobia or an inability to provide venous blood samples.


Assuntos
Ácidos Nicotínicos , Humanos
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 271: 120862, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35085996

RESUMO

A highly sensitive and specific visual detection method for aflatoxin B1 (AFB1) based on the target specificity of aptamer, rolling circle amplification (RCA) and enzyme catalysis biological amplification effect has been established. In this work, AFB1 aptamer immobilized on the surface of magnetic beads (MB) serves as a molecular recognition probe. In the absence of AFB1, the aptamer and auxiliary linking probe (LP) maintain a double stranded state due to partial base pair complementarities. By contrast, in the presence of AFB1, the aptamer preferentially binds to AFB1 specifically, and the LP later restores to a single stranded state. Subsequently, the RCA reaction is triggered by above-mentioned single stranded LP to generate long DNA strands, which are employed to capture amounts of signal probes (SP) and horse radish peroxidases (HRP). Finally, amounts of HRP catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 and leads to a dramatic color change of the solution from colorlessness to deep blue as a signal indicator, obtaining a high sensitivity, high specificity and visual detection of AFB1. Under optimal conditions, a good linear detection range (0.5-40 pg·mL-1) was achieved, and the limit of detection (LOD) was 0.13 pg·mL-1. Besides, the proposed aptasensor showed excellent specificity for AFB1 compared with five other mycotoxins. More than that, all reactions occur on the surface of the magnetic beads, which not only facilitates the detection operation process including the efficient isolation and collection of AFB1 from sample matrix, but also gets better selectivity and stronger resistibility to target analyte in complex sample matrix, adequately indicating its potential application in AFB1 practical detection.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Aflatoxina B1/análise , Técnicas Biossensoriais/métodos , Contaminação de Alimentos/análise , Ouro , Peróxido de Hidrogênio , Limite de Detecção
15.
IEEE Trans Vis Comput Graph ; 28(12): 4172-4185, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34018933

RESUMO

Multiple cylinders detection from large-scale and complex point clouds is a historical but challenging problem, considering the efficiency and accuracy. We propose a novel framework, named slicing-tracking-detection (STD), that detects multiple cylinders accurately and simultaneously from point clouds of large-scale and complex process plants. In this framework, the 3D cylinder detection problem is reformulated as a cylinder ingredients tracking task based on multi-object tracking (MOT). First, we generate slices from the input point cloud, and render them to slice sequence. Then, the cycle of a cylinder is modeled with a Markov Decision Process (MDP), where the ingredient is tracked with a template and the miss tracking is associated with ingredient proposals through reinforcement learning. Finally, by applying MDP for each cylinder, multiple cylinders can be detected simultaneously and accurately. Extensive experiments show that the proposed STD framework can significantly outperform the state-of-the-art approaches in efficiency, accuracy, and robustness. The source code is available at http://zhiyongsu.github.io.

16.
Nanomicro Lett ; 13(1): 85, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-34138298

RESUMO

Neuromorphic computing simulates the operation of biological brain function for information processing and can potentially solve the bottleneck of the von Neumann architecture. This computing is realized based on memristive hardware neural networks in which synaptic devices that mimic biological synapses of the brain are the primary units. Mimicking synaptic functions with these devices is critical in neuromorphic systems. In the last decade, electrical and optical signals have been incorporated into the synaptic devices and promoted the simulation of various synaptic functions. In this review, these devices are discussed by categorizing them into electrically stimulated, optically stimulated, and photoelectric synergetic synaptic devices based on stimulation of electrical and optical signals. The working mechanisms of the devices are analyzed in detail. This is followed by a discussion of the progress in mimicking synaptic functions. In addition, existing application scenarios of various synaptic devices are outlined. Furthermore, the performances and future development of the synaptic devices that could be significant for building efficient neuromorphic systems are prospected.

17.
Int J Dermatol ; 60(11): 1411-1417, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34057203

RESUMO

BACKGROUND: As an immune regulator expressed on the surface of activated T cells, programmed cell death 1 (PDCD1) plays an important role in psoriasis. However, whether PDCD1 genetic polymorphism is associated with psoriasis has yet to be explored. OBJECTIVE: To study the association between polymorphisms of the immune-related gene PDCD1 and psoriasis susceptibility in the Chinese population, to illustrate the genetic mechanism of psoriasis and provide new research ideas for the diagnosis and treatment of psoriasis (PS). METHODS: Overall, 128 psoriasis patients and 88 healthy controls were included in this study. Using polymerase chain reaction (PCR)-Sanger sequencing analysis, six PDCD1 single nucleotide polymorphisms (SNPs) were sequenced: PD1.1, PD1.3, PD1.4, PD1.5, PD1.6, and PD1.9. RESULTS: Among the six tested SNPs, PD1.6 showed a significant association with psoriasis in genotype and allele frequency distribution. The G allele of PD1.6 increased the risk of psoriasis (P = 0.03). In contrast, the other five SNPs failed to show association with psoriasis. Further analysis within the patient group showed that the frequency of the PD1.6 G allele was relatively high in severe psoriasis, but the difference was nonsignificant. CONCLUSION: PDCD1 gene polymorphism is associated with psoriasis. The population carrying PD1.6 allele G are at a higher risk of developing psoriasis, though the severity of psoriasis does not correlate with PD1.6 polymorphism.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptor de Morte Celular Programada 1 , Psoríase/genética , China , Frequência do Gene , Humanos , Receptor de Morte Celular Programada 1/genética
18.
Cell Death Discov ; 7(1): 111, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34001865

RESUMO

Variants in the melanocortin-1 receptor (MC1R) gene, encoding a trimeric G-protein-coupled receptor and activated by α-melanocyte-stimulating hormone (α-MSH), are frequently associated with red or blonde hair, fair skin, freckling, and skin sensitivity to ultraviolet (UV) light. Several red hair color variants of MC1R are also associated with increased melanoma risk. MC1R variants affect melanoma risk independent of phenotype. Here, we demonstrated that MC1R is a critical factor in chromosome stability and centromere integrity in melanocytes. α-MSH/MC1R stimulation prevents melanocytes from UV radiation-induced damage of chromosome stability and centromere integrity. Mechanistic studies indicated that α-MSH/MC1R-controlled chromosome stability and centromeric integrity are mediated by microphthalmia-associated transcription factor (Mitf), a transcript factor needed for the α-MSH/MC1R signaling and a regulator in melanocyte development, viability, and pigment production. Mitf directly interacts with centromere proteins A in melanocytes. Given the connection among MC1R variants, red hair/fair skin phenotype, and melanoma development, these studies will help answer a question with clinical relevance "why red-haired individuals are so prone to developing melanoma", and will lead to the identification of novel preventive and therapeutic strategies for melanomas, especially those with redheads.

19.
Exp Ther Med ; 21(4): 336, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33732309

RESUMO

Osteoporosis is a common complication of long-term use of glucocorticoids (GCs) characterized by the loss of bone mass and damage of the microarchitecture as well as osteoblast dysfunction. Previous studies have demonstrated that microRNA-22 (miR-22) is the negative modulator of osteogenesis that may target caveolin-3 (CAV3), which has been reported to enhance bone formation and inhibit the progression of osteoporosis as well as apoptosis. The present study aimed to investigate whether miR-22 may be involved in dexamethasone (DEX)-induced inhibition of osteoblast differentiation and dysfunction by regulating CAV3 expression. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure the expression of miR-22 and western blotting was performed to determine protein levels. The results demonstrated that miR-22 expression was upregulated in DEX-treated osteoblastic cells compared with the control group. In addition, miR-22 mimic aggravated, whereas miR-22 inhibitor mitigated DEX-induced damage in osteoblastic cells compared with the control groups. Additionally, CAV3 was identified as the target of miR-22 in osteoblasts using RT-qPCR, western blotting and dual-luciferase reporter gene assay analysis. The results also demonstrated that silencing of CAV3 blocked the beneficial effects of miR-22 inhibitor against DEX-induced cell damage and apoptosis in osteoblasts, as evidenced by the increased expression levels of cleaved caspase-3, Bax and alkaline phosphatase activity as well as decreased cell viability and Bcl-2 levels. Collectively, these results indicate a novel molecular mechanism by which miR-22 contributes to DEX-induced osteoblast dysfunction and apoptosis via the miR-22/CAV3 pathway.

20.
Free Radic Biol Med ; 166: 226-237, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33636337

RESUMO

Oxidative stress plays an important role in the pathogenesis of osteoporosis and impaired bone formation. However, the mechanisms behind which oxidative stress represses bone formation remains unclear. TP53INP2, a target of the tumor suppressor p53, is ubiquitously expressed in various cell types including BMSCs and contributes to autophagosome formation by recruiting ubiquitinated substrates to autophagosomes for degradation. However, little is known about its function in BMSCs and its relation to osteoporosis. In this study, first, we verified that the expression of TP53INP2 was persistently decreased in BMSCs derived from osteoporosis patients and OVX mice, and that the antioxidant N-acetylcysteine could ameliorate this decreased TP53INP2 level in vitro. Second, we identified that the mRNA and protein levels of TP53INP2 decreased in BMSCs under H2O2 induced oxidative stress in a dose-dependent manner, with resultant co-location of LC3 and TP53INP2. Additionally, the autophagy-lysosome system was involved in the degradation process of TP53INP2 and applying autophagy inhibitors (Baf-A1) could significantly increase the TP53INP2 levels in murine and human BMSCs under oxidative stress. Third, gain- and loss-of-function assays revealed that knockdown of TP53INP2 inhibited osteogenic differentiation of BMSCs, while overexpression of TP53INP2 promoted osteogenic differentiation of BMSCs in vitro. Further analysis demonstrated that TP53INP2 promoted osteogenic differentiation of BMSCs by activating Wnt/ß-cantenin signaling. DKK1, an inhibitor of Wnt signaling, resulted in osteogenic defects of BMSCs that had over-expressed TP53INP2. Lithium, a Wnt/ß-catenin activator, improved the mineralization ability in TP53INP2-knockdown BMSCs. Moreover, restoring TP53INP2 levels recovered OVX-derived BMSCs osteogenic differentiation and attenuated bone loss in OVX mice. Taken together, our study indicated that oxidative stress-induced downregulation of TP53INP2 suppressed osteogenic differentiation of BMSCs during osteoporosis and was mediated by the autophagy degradation pathway. These findings may introduce a novel therapeutic target for osteoporosis.


Assuntos
Células-Tronco Mesenquimais , Osteoporose , Animais , Autofagia , Diferenciação Celular , Regulação para Baixo , Humanos , Peróxido de Hidrogênio/toxicidade , Camundongos , Proteínas Nucleares , Osteogênese , Osteoporose/genética , Estresse Oxidativo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...