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1.
Front Endocrinol (Lausanne) ; 15: 1335810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352715

RESUMO

Background & aims: Existing evidence on the possible effects of probiotics on obese or overweight adolescents has not been fully established. Therefore, the aim of this study was to explore the effects of probiotic supplementation on anthropometric indices, inflammatory markers and metabolic indices in obese or overweight adolescents. Methods: The literature up to March 2023 related to probiotic intervention in obese or overweight adolescents was searched and screened from multiple databases, including the CNKI(China national knowledge infrastructure), CBM(Chinese biomedical literature database), PubMed, EmBase, and Cochrane library databases. All randomized controlled trials using probiotic supplements in obese or overweight adolescents were included in this systematic review and meta-analysis. Results: A total of 8 studies that met the inclusion criteria were included in this study. There were 201 cases in the experimental group (probiotic treatment) and 190 cases in the control group. Compared to the control group, probiotic intervention in adolescents resulted in a decrease in body mass index, fasting blood glucose and C-reactive protein with WMD(Weighted mean difference) and 95% CI of -2.53 (-4.8 to -0.26) kg/m2, -0.80 (-1.13 to -0.47) mol/L and -0.24 (-0.43 to -0.05) mg/L, respectively. No significant changes were found in weight, waist circumference, waist-to-hip ratio, insulin, Homeostatic Model Assessment of insulin resistance, interleukin 6, tumor necrosis factor alpha and so on; however, an unfavorable elevated effect in total cholesterol, triglycerides, and low-density lipoproteins was detected with WMD and 95% CI of 0.06 (0.02 to 0.09) mmol/L, 0.18 (0.14 to 0.21) mmol/L, and 0.19 (0.18 to 0.20) mmol/L, respectively. Conclusion: According to our results, probiotic supplementation was beneficial in managing metabolic indicators such as fasting blood glucose, body mass index and inflammation-related C-reactive protein in overweight or obese adolescents. Further large scale studies are warranted to confirm present findings and to identify the effects and mechanisms to provide more precise evidence for clinical intervention. Systematic review registration: doi: 10.37766/inplasy2024.1.0081, identifier INPLASY202410081.


Assuntos
Sobrepeso , Probióticos , Adolescente , Humanos , Glicemia , Proteína C-Reativa , Obesidade/tratamento farmacológico , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Phys Chem Lett ; 14(28): 6328-6338, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37417732

RESUMO

To further ameliorate current additive engineering of perovskites for viable applications, the inherent limitations should be overcome; these include weakened coordination of the dopants to the [PbI6]4- octahedra during crystallization and ubiquity of ineffective bonding sites. Herein, we introduce a facile strategy for synthesizing a reduction-active antisolvent. Washing with reduction-active PEDOT:PSS-blended antisolvent substantially enhances the intrinsic polarity of the Lewis acid (Pb2+) in [PbI6]4- octahedra, which causes significant strengthening of the coordinate bonding between additives and perovskite. Thus, coordination of the additive to the perovskite becomes much stable. Additionally, the enhanced coordination ability of Pb2+ can enhance the effective bonding sites and further enhance the efficacy of additive optimization to the perovskite. Here, we demonstrate five different additives as dopant bases and repeatedly verify the universality of this approach. The photovoltaic performance and stability of doped-MAPbI3 devices are further improved, revealing the advanced potential of additive engineering.

3.
Plant Physiol Biochem ; 195: 310-321, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36657296

RESUMO

R2R3-MYB transcription factors play an important role in the synthesis of phenylpropanoid-derived compounds, which in turn provide salt tolerance in plant. In this study, we found that the expression of foxtail millet R2R3-MYB factor SiMYB16 can be induced by salt and drought. SiMYB16 is localized in the nucleus and acts as a transcriptional activator. Phylogenetic analysis indicates that SiMYB16 belongs to the R2R3-MYB transcription factor family subgroup 24. Transgenic rice expressing SiMYB16 (OX16) had a higher survival rate, lower malondialdehyde content, and heavier fresh weight compared with type (WT) under salt stress conditions. The transgenic plants also had a higher germination rate in salt treatment conditions and higher yield in the field compared with wild-type plants. Transcriptome analysis revealed that the up-regulated differential expression genes in the transgenic rice were mainly involved in phenylpropanoid biosynthesis, fatty acid elongation, phenylalanine metabolism, and flavonoid biosynthesis pathways. Quantitative real-time PCR analysis also showed that the genes encoding the major enzymes in the lignin and suberin biosynthesis pathways had higher expression level in SiMYB16 transgenic plants. Correspondingly, the content of flavonoid and lignin, and the activity of fatty acid synthase increased in SiMYB16 transgenic rice compared with wild-type plants under salt stress treatment. These results indicate that SiMYB16 gene can enhance plant salt tolerance by regulating the biosynthesis of lignin and suberin.


Assuntos
Oryza , Setaria (Planta) , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tolerância ao Sal/genética , Setaria (Planta)/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Lignina/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Flavonoides/metabolismo , Secas
4.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615608

RESUMO

The synthesis of α,α-dideuterio alcohols has been achieved via single electron transfer reductive deuteration of acyl chlorides using SmI2 and D2O. This method is distinguished by its remarkable functional group tolerance and exquisite deuterium incorporation, which has also been applied to the synthesis of valuable deuterated agrochemicals and their building blocks.


Assuntos
Álcoois , Cloretos , Deutério , Iodetos
5.
Appl Biochem Biotechnol ; 195(9): 5299-5311, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35622274

RESUMO

Diabetic retinopathy (DR) is the key cause of blindness and visual impairment in diabetes patients around the world. The high levels of oxidative stress in diabetes patients cause diabetic retinopathy. In addition to being an antioxidant, Bergenin also works as an immunosuppressant, an anti-inflammatory, and anticarcinogenic against hepatocarcinoma. This study examined the effects of Bergenin on diabetic retinopathy rats, using Streptozotocin (STZ) intraperitoneally to induce diabetes in rats. The animals were divided into four groups (n = 6), including a normal control (Group I), diabetic control (Group II), Bergenin (25 mg/kg) (Group III), and metformin (350 mg/kg) (Group IV). As previously mentioned, each animal received treatment for 60 days. To induce DR, rats were administered STZ (60 mg/kg) intraperitoneally for 60 days. Standard methods were utilized to measure the body weight of rats, blood glucose levels. We measured lipid profiles (Triglycerides, cholesterol, LDL, and HDL), inflammatory markers, and antioxidant levels with their respective kits. Analysis of retinal tissue morphometry and MMP-9, VEGF, and MCP-1 levels in serum was performed. Our research examined the expression levels of target genes (TNF-α, IL-1ß, and IL-6) using RT-PCR analysis. STZ-induced animals that were treated with Bergenin had less food intake, lower blood glucose, and improved body weight. Bergenin significantly suppressed levels of pro-inflammatory cytokines, cholesterol, TG, LDL, AI, MMP-9, VEGF, and MCP-1 and increased the level of HDL and antioxidant enzymes in STZ-induced DR rats. As well as increasing antioxidant levels, reducing retinal thickness, and increasing cell numbers, Bergenin also lessened DR remarkably. The results of this study demonstrated that Bergenin effectively inhibited STZ-induced DR in rats.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Ratos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Estreptozocina/farmacologia , Antioxidantes/farmacologia , Metaloproteinase 9 da Matriz , Ratos Sprague-Dawley , Glicemia/análise , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo , Peso Corporal
6.
Pathol Res Pract ; 238: 154115, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36084427

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers, and has an extremely poor prognosis. Our previous study confirmed that the microRNA miR-361-5p inhibited the proliferation, metastasis, invasiveness, and epithelial-to-mesenchymal transition (EMT) process of HCC by targeting the transcription factor Twist1. Long non-coding RNAs (lncRNAs) are key regulators of processes such as cell differentiation, inflammation, tumor formation, and immune escape. However, the underlying interactions between the lncRNA LINC00992, miR-361-5p, and Twist1 in HCC progression is still elusive. In the current study, the DIANA-lncBase database was used to identify regulatory genes upstream of miR-361-5p. Reverse transcription-quantitative PCR (RT-qPCR) was used to quantify the expression of the genes encoding LINC00992, miR-361-5p, and Twist1 in HCC cells. The cell counting kit-8 (CCK-8) was used to measure HCC cell proliferation and Transwell was used to measure HCC cell migration and invasion. The dual-luciferase reporter assay and RNA pull-down assay were performed to examine the interaction between LINC00992 and miR-361-5p. Western blotting was used to detect the levels of Twist1 protein. The result confirmed that, among three lncRNAs tested, miR-361-5p was the one most significantly affected by LINC00992. RT-qPCR revealed that LINC00992 was highly expressed in HCC tissues and cells. The follow-up results showed that the expression of LINC00992 and miR-361-5p in HCC tissues were closely correlated with the rate of metastasis or recurrence of the HCC patients. Our result showed that the expression of miR-361-5p was lower in the LINC00992 (+) group than in the LINC00992 (-) group. CCK-8 and Transwell showed that LINC00992 promoted HCC cell proliferation, migration, and invasion, whereas dual-luciferase reporter assay and RNA pull-down assay showed that LINC00992 combined with miR-361-5p to act as a miRNA decoy in HCC. RT-qPCR and Western blotting confirmed that LINC00992 upregulated the expression of the Twist1 gene in HCC cells by downregulating expression of miR-361-5p. CCK-8 and Transwell assays confirmed that LINC00992 promoted the proliferation, metastasis, and invasiveness of HCC cells by downregulating miR-361-5p levels and consequently upregulating Twist1 expression, implying that these three elements may be promising targets for HCC therapy.

7.
Front Public Health ; 10: 925668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072378

RESUMO

In recent years, the development of tobacco control actions in China and the changes in people's health concepts have slowed the development of the tobacco industry. As an important strategic partner of tobacco sales companies, tobacco retailers are the key link between tobacco commercial enterprises and consumers. How to improve the work engagement level of tobacco retailers is an urgent issue for tobacco business enterprises. On the basis of job demands-resources (JD-R) theory, the mechanisms of the effects of job resources and demands on tobacco retailers' work engagement were explored. Results showed that (1) The negative path of job demands influencing tobacco retailers' work engagement was supported, and job crafting played a mediating role in it. (2) The positive path of job resources influencing tobacco retailers' work engagement was supported, and job crafting played a mediating role in it. (3) Servant leadership moderated the influence of job resources and demands on job crafting. Higher level of servant leadership brings the stronger effect of job resources on job crafting and the weaker effect of job demands on job crafting. (4) The mediating effect of job crafting between JD-R and work engagement was moderated by servant leadership. The higher level of servant leadership strengthened the mediating role of job crafting between job demands and work engagement, whereas it weakened the mediating role of job crafting between job demands and work engagement. This study enriches the research on application fields and boundary conditions of JD-R theory and provides practical guidance for improving the work engagement level of tobacco retailers.


Assuntos
Nicotiana , Engajamento no Trabalho , Humanos , Liderança , Inquéritos e Questionários , Uso de Tabaco
8.
IEEE Trans Biomed Circuits Syst ; 16(5): 962-971, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35994551

RESUMO

Currently, there is no suitable solution for the point-of-care diagnosis of knee injuries. A potential portable and low-cost technique for accessing and monitoring knee injuries is bioimpedance measurement. This study validated the feasibility of the bipolar electrode configuration for knee bioimpedance measurement with two electrodes placed on a fixed pair of knee acupuncture locations called Xiyan. Then, the study collected 76 valid samples to investigate the relationship between bioimpedance and knee injuries, among whom 39 patients have unilateral knee injuries, and 37 individuals have healthy knees. The self-contrast results indicated that knee injuries caused a reduction of bioimpedance of the knee by about 5% on average, which was detectable at around 100 kHz (p ≈ 0.001). Furthermore, the results analyzed by principal component analysis and support vector machines show that the detection sensitivity can reach 87.18% using the leave-one-out cross-validation. We also proposed a low-cost and portable bioimpedance measurement device that meets the needs for measuring knee joint bioimpedance.


Assuntos
Terapia por Acupuntura , Traumatismos do Joelho , Humanos , Impedância Elétrica , Traumatismos do Joelho/diagnóstico , Eletrodos
9.
Org Lett ; 24(29): 5319-5323, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35856804

RESUMO

An efficient one-pot sequential hydrogen isotope exchange (HIE)/reductive deuteration approach was developed for the preparation of α,ß-deuterated alcohols using ketones as the precursors. The HIE step can also be used for the synthesis of α-deuterated ketones. This method has been applied in the synthesis of four deuterated drug and MS internal standards.


Assuntos
Álcoois , Hidrogênio , Deutério , Óxido de Deutério , Cetonas
10.
Chemistry ; 28(43): e202200850, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35587563

RESUMO

The intrinsic defects in perovskite film can serve as non-radiative recombination center to limit the performance and stability of metal halide perovskite solar cells (PSCs). The additive engineering in perovskite film is always applied to produce high-efficiency PSCs in recent years. Here, a typical donor-acceptor (D-A) structured aggregation-induced emission (AIE) molecule tetraphenylethene-2-dicyano-methylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TPE-TCF) was introduced into perovskite film. The D-A structure of TPE-TCF molecule provided additional charge transfer channels, contributing to transporting electron of TPE-TCF-based device. The cyano (C≡N) of TPE-TCF can interact with the uncoordinated Pb to from a relatively stable intermediate, PbI2 ⋅TPE-TCF, resulting in the slower crystal growth, reduced the defects at the grain boundaries and suppressed carrier recombination. As a consequence, the power conversion efficiency (PCE) of TPE-TCF-modified PSCs achieved a remarkably enhanced from 15.63 to 19.66 % with negligible hysteresis, which was prominent in methylammonium lead iodide-based devices fabricated under ambient condition. Furthermore, the PSCs modified by AIE molecule possessed an outstanding stability and maintain about 86 % of the initial PCE after 300 h storage in air at 25-35 °C with a high relative humidity (RH) of ≈85 %. This work suggests that incorporating AIE molecule into perovskite is a promising strategy for facilitating high-performance PSCs commercialization in ambient environment without glovebox.

11.
Nat Commun ; 13(1): 50, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013196

RESUMO

Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4 N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.


Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Arginina/metabolismo , Fenômenos Mecânicos , Osteogênese/fisiologia , Amidoidrolases/genética , Animais , Osso e Ossos , Feminino , Hidrólise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
12.
Front Psychol ; 12: 732660, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899472

RESUMO

The projected growth and rapid technological development in maritime transportation will create demand for a newly skilled and motivated workforce in the port sector. Thus, it is important for ports to attract, recruit and retain talented employees to promote innovation and enhance competitive advantages. This manuscript focuses on the welfare and talent of port staff from the perspective of person-environment (P-E) fit. Using polynomial regression with response surface analysis, this study explores the effect of P-E fit on job satisfaction, work engagement and innovation performance, and bootstrapping is applied to confirm the mediating roles of job satisfaction and work engagement in the relationship between P-E fit and innovation performance. Results show that (1) need-supply (N-S) fit and demands-abilities (D-A) fit improved port employees' job satisfaction, work engagement and innovation performance, and the impacts on work engagement and innovation performance show an inverted "U" and "U" shape, respectively; (2) D-A fit is more important when job satisfaction plays a mediating role; and (3) N-S fit makes a greater contribution when work engagement mediates the effect of P-E fit on the innovation performance. These findings contribute to P-E fit research as well as to human resource management practices in ports.

13.
ACS Omega ; 6(37): 23683-23690, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34568648

RESUMO

A novel, hyperbranched polysiloxane (HBPSi) is successfully synthesized via hydrolysis using γ-methacryloxypropyl trimethoxysilane (A174) and deionized water, under catalyst-free conditions. Then, for the first time, the HBPSis are used to modify a 3D printing light-curing epoxy resin. Thermogravimetry results showed that the addition of HBPSi improved the heat resistance of the epoxy resin. Experimental results also show that the addition of HBPSi simultaneously improves tensile strength, elongation at break, and impact strength. In particular, a great increase in the toughness of 3D printing light-curing epoxy resin is observed, with 5 wt % HBPSi loading. These results indicate that the HBPSi containg OH- and Si-O-Si can be potentially effective at improving the performance of the 3D printing light-curing epoxy resin. This investigation suggests that the method proposed herein is a new approach to develop the performance of 3D printing light-curing epoxy resin for cutting-edge industries, especially those that simultaneously have outstanding thermal resistance and toughness.

14.
Pain Physician ; 24(6): E803-E810, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34554700

RESUMO

BACKGROUND: Percutaneous kyphoplasty (PKP) is a widely accepted surgical treatment modality for painful osteoporotic vertebral compression fractures. The risk factors cause of subsequent vertebral fractures after PKP are debated. OBJECTIVES: To evaluate risk factors for the occurrence of new vertebral compression fractures after PKP. STUDY DESIGN: A retrospective study. SETTING: A single-center inpatient population. METHODS: A total of 921 patients (1,152 vertebrae) with PKP were investigated. Among those patients, 111 patients (155 levels) incurred refractures after PKP. RESULTS: The average bone mineral density was -3.27 in the "refracture"group and -3.00 in the "no fracture" group (P = 0.031). Morbidities of women were significantly higher in the "refracture" group (90.99%) compared with the "no fracture" group (81.73%) (P = 0.015). Among the basic diseases, several diseases (history of previously fracture, previously osteoporosis, gallstone disease, stomach disease, and ovariectomy) are associated with refractures after PKP (P < 0.05). And antiosteoporotic treatment (calcium + vitamin D or zoledronate) after PKP can also significantly reduce the occurrence of refracture (P < 0.000). In addition, logistic regression analysis also showed that most of the above contents had significant correlation with the refracture after PKP (P < 0.05), except for gallstone disease (P = 0.362). LIMITATIONS: Retrospective study, single center. CONCLUSION: Osteoporosis is the main cause of refracture after PKP. Elderly women were found to be more susceptible than elderly men to refracture. Patients with a history of previously fracture, previously osteoporosis, stomach ulcer, and ovariectomy are more likely to be refracture. Antiosteoporosis treatment (calcium + vitamin D or zoledronate) after PKP can reduce the risk of refracture.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Idoso , Cimentos Ósseos , Feminino , Fraturas por Compressão/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
15.
Chem Commun (Camb) ; 57(42): 5195-5198, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33908475

RESUMO

A highly chemoselective reductive deuteration of acyl fluorides to provide α,α-dideuterio alcohols with exquisite levels of deuterium incorporation was developed using SmI2 and D2O as the deuterium source. This method introduces acyl fluorides as attractive radical precursors for the generation of reactive acyl-type fluoride ketyls that should find widespread application in many synthetic strategies involving single electron transfer processes.

16.
Exp Ther Med ; 21(4): 364, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33732337

RESUMO

Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease. Recently, inflammatory factors have been confirmed to be responsible for the brain damage associated with SAH. Therefore, studying the post-SAH inflammatory reaction may clarify the mechanism of SAH. Mitogen and stress-activated protein kinase 1 (MSK1) causes the phosphorylation of NF-κB and regulates the activity of pro-inflammatory transcription factors. The present study aimed to identify the potential role of MSK1 in inflammation and brain damage development following SAH. A cisterna magna blood injection model was established in Sprague-Dawley rats. Hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction assays and double immunofluorescence staining were used to analyze the role of MSK1, IL-1ß and TNF-α in the inflammatory process after SAH. In a model of lipopolysaccharide-induced astrocyte inflammation, the effect of overexpressing MSK1 overexpression was analyzed by western blot analysis. The results demonstrated that MSK1 expression were negatively correlated with TNF-α and IL-1ß expression levels, and reached peak levels 2 days after TNF-α and IL-1ß. The double immunofluorescence staining results showed that the expression of MSK1 was in the same plane of view as TNF-α and IL-1ß in the brain cortex. Furthermore, the in vitro studies indicated that the overexpression of MSK1 inhibited the expression of TNF-α and IL-1ß following LPS challenge. These results imply that MSK1 may be involved in the inflammatory reaction following SAH, and may potentially serve as a negative regulator of inflammation.

17.
Andrologia ; 53(5): e14016, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33598946

RESUMO

Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA-21 suppression considerably hindered PC3/DOX cell viability. miR-21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.


Assuntos
MicroRNAs , Neoplasias da Próstata , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Masculino , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética
18.
J Org Chem ; 86(3): 2907-2916, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33486945

RESUMO

Selective introduction of the deuterium atom into the α-position of amines is important for the development of all types of novel deuterated drugs and agrochemicals due to the pervasive presence of amines. In this study, we report the first general single-electron-transfer reductive deuteration of both ketoximes and aldoximes using SmI2 as an electron donor and D2O as a deuterium source for the synthesis of α-deuterated primary amines with excellent levels of deuterium incorporations (>95% [D]). This protocol exhibits excellent chemoselectivity and tolerates a variety of functional groups. The potential application of this new method was showcased in the synthesis of deuterated drugs, such as rimantadine-d4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone, and a series of building blocks for the rapid and general assembly of deuterated drugs and pesticides.


Assuntos
Aminas , Oximas , Deutério
19.
Biomed Res Int ; 2020: 8891876, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381597

RESUMO

MicroRNA-361-5p (miR-361-5p) is a tumor suppressor miRNA that is dysregulated in several types of human cancer. However, the functional significance of miR-361-5p in hepatocellular carcinoma (HCC) is unclear. This study explored the biological function of miR-361-5p in regulating the progression of HCC and the underlying molecular mechanism. RT-qPCR analysis showed that miR-361-5p was downregulated in HCC tissues and cell lines. Functional analysis revealed that miR-361-5p acted as a tumor suppressor, inhibiting cell proliferation, migration, and invasion in HCC cell lines. Bioinformatics analyses identified Twist1 as a direct target of miR-361-5p, which was validated by dual-luciferase reporter assays, RT-qPCR, and western blotting. Rescue experiments indicated that Twist1 may mediate the tumor-suppressive effect of miR-361-5p in HCC cells, and this was supported by the effect of miR-361-5p on inhibiting the epithelial-mesenchymal transition (EMT) by targeting Twist1. This study is the first to suggest that miR-361-5p inhibits tumorigenesis and EMT in HCC by targeting Twist1. These findings are valuable for the diagnosis and clinical management of HCC.


Assuntos
Carcinoma Hepatocelular , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas , MicroRNAs , Proteínas Nucleares , Proteína 1 Relacionada a Twist , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
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