Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 143
Filtrar
1.
Environ Pollut ; 292(Pt A): 118341, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637832

RESUMO

With the development of marine oil industry, oil spill accidents will inevitably occur, further polluting the intertidal zone and causing biological poisoning. The muddy intertidal zone and Boleophthalmus pectinirostris were selected as the research objects to conduct indoor acute exposure experiments within 48 h of crude oil pollution. Statistical analysis was used to reveal the activity changes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in the gills and liver of mudskipper. Then, integrated biomarker response (IBR) indicators were established to comprehensively evaluate the biological toxicity. The results showed that the activities of SOD, CAT and GST in livers were higher than those in gills, and the maximum induction multipliers of SOD, CAT and GPx in livers appeared earlier than those in gills. Both SOD and GPx activities were induced at low pollutant concentrations and inhibited at high pollutant concentrations. For the dose-effect, the change trends of CAT and SOD were roughly inversed. There was substrate competition between GPx and CAT, with opposite trends over time. The activating mechanism of GST was similar to that of GPx, and the activation time was earlier than that of GPx. In terms of dose-effect trends, the IBR showed that the antioxidant enzymes activities in biological tissues were induced by low and inhibited by high pollutant concentrations. Overall, SOD and GPx in gills and CAT and GST in livers of the mudskippers were suitable as representative markers to comprehensively analyze and evaluate the biotoxicity effects of oil pollution in the intertidal zone. The star plots and IBR values obtained after data standardization were consistent with the enzyme activity differences, which can be used as valid supplementary indexes for biotoxicity evaluation. These research findings provide theoretical support for early indicators of biological toxicity after crude oil pollution in intertidal zones.


Assuntos
Antioxidantes , Petróleo , Animais , Biomarcadores/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo , Petróleo/toxicidade
2.
Front Pharmacol ; 12: 721869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795578

RESUMO

Melatonin plays a critical role in the pathophysiological process including circadian rhythm, apoptosis, and oxidative stress. It can be synthesized in ocular tissues, and its receptors are also found in the eye, triggering more investigations concentrated on the role of melatonin in the eye. In the past decades, the protective and therapeutic potentials of melatonin for ocular diseases have been widely revealed in animal models. Herein, we construct a knowledge map of melatonin in treating ocular diseases through bibliometric analysis and review its current understanding and clinical evidence. The overall field could be divided into twelve topics through keywords co-occurrence analysis, in which the glaucoma, myopia, and retinal diseases were of greatest research interests according to the keywords burst detection. The existing clinical trials of melatonin in ocular diseases mainly focused on the glaucoma, and more research should be promoted, especially for various diseases and drug administration. We also discuss its bioavailability and further research topics including developing melatonin sensors for personalized medication, acting as stem cell therapy assistant drug, and consuming food-derived melatonin for facilitating its clinical transformation.

3.
Environ Res ; : 112453, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843726

RESUMO

To explore green technology for wheat straw pretreatment, this study combined the microwave or hydrothermal with ionic liquid ([Bmim][OAc]) on wheat straw followed by rumen fermentation. The optimal conditions of microwave assisted ionic liquids pretreatment (M-I) and hydrothermal assisted ionic liquids pretreatment (H-I) treatment were 360 W and 200 °C, and the corresponding lignin removal rates reached 35.3% and 25.4%, respectively. Rumen fermentation showed that the highest volatile fatty acid (VFA) yield was found in M-I group, followed by H-I group at 234 and 180 mg/g, respectively. As for enzymatic hydrolysis, the saccharification rates at 3 days of M-I (360 W) and H-I (200 °C) were determined to be 393 and 320 mg/g. The optimal ionic liquid dosage was determined to be 30% in consideration of cost and VFA conversion rate. M-I pretreatment plus the rumen fermentation enjoyed the benefit of no enzyme addition and high product recovery, which was worth further investigating.

4.
Eur J Med Chem ; 227: 113871, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638033

RESUMO

The ubiquitination of the hypoxia-inducible factor-1α (HIF-1α) is mediated by interacting with the von Hippel-Lindau protein (VHL), and is associated with cancer, chronic anemia, and ischemia. VHL, an E3 ligase, has been reported to degrade HIF-1 for decades, however, there are few successful inhibitors currently. Poor understanding of the binding pocket and a lack of in-depth exploration of the interactions between two proteins are the main reasons. Hence, we developed an effective strategy to identify and design new inhibitors for protein-protein interaction targets. The hydroxyproline (Hyp564) of HIF-1α contributed the key interaction between HIF-1α and VHL. In this study, detailed information of the binding pocket were explored by alanine scanning, site-directed mutagenesis and molecular dynamics simulations. Interestingly, we found the interaction(s) between Y565 and H110 played a key role in the binding of VHL/HIF-1α. Based on the interactions, 8 derivates of VH032, 16a-h, were synthesized by introducing various groups bounded to H110. Further assay on protein and cellular level exhibited that 16a-h accessed higher binding affinity to VHL and markable or modest improvement in stabilization of HIF-1α or HIF-1α-OH in HeLa cells. Our work provides a new orientation for the modification or design of VHL/HIF-1α protein-protein interaction inhibitors.

5.
Pancreas ; 50(6): 882-889, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34347728

RESUMO

OBJECTIVE: We aimed to assess the role of serum chromogranin A (CgA) in monitoring disease status and treatment response in patients with pancreatic neuroendocrine neoplasms (pNENs). METHODS: We included posttherapy pNENs patients with measured serum CgA levels who underwent 68Ga-labeled tetraazacyclododecanetetraacetic acid-peptide positron emission tomography (PET) imaging between April 2017 and January 2020. Serum CgA levels were determined by enzyme-linked immunosorbent assay. Tumor response was assessed according to the PET response evaluation criteria in solid tumors. RESULTS: Seventy-seven patients with 101 events were included in this study. Serum CgA levels were significantly higher in patients with active disease and metastasis. The optimal cutoff values for CgA for active and metastatic pNENs diagnosis after treatment were 52.39 (77.8% sensitivity, 80.7% specificity) and 60.18 ng/mL (73.9% sensitivity, 73.1% specificity), respectively. Based on 18 patients with serial CgA measurements and PET imaging, the optimal changes in CgA levels for predicting disease remission and progression were a 28.5% decrease (71.4% sensitivity, 88.2% specificity) and a 21.0% increase (100.0% sensitivity, 75.0% specificity), respectively. CONCLUSIONS: We concluded that serum CgA levels are associated with disease status and treatment response and may thus provide a helpful biomarker for the monitoring and clinical management of patients with pNENs.

6.
Angew Chem Int Ed Engl ; 60(40): 21884-21889, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34374188

RESUMO

Stimulating photosensitizers (PS) by Cerenkov radiation (CR) can overcome the light penetration limitation in traditional photodynamic therapy. However, separate injection of radiopharmaceuticals and PS cannot guarantee their efficient interaction in tumor areas, while co-delivery of radionuclides and PS face the problem of nonnegligible phototoxicity in normal tissues. Here, we describe a 131 I-labeled smart photosensitizer, composed of pyropheophorbide-a (photosensitizer), a diisopropylamino group (pH-sensitive group), an 131 I-labeled tyrosine group (CR donor), and polyethylene glycol, which can self-assemble into nanoparticles (131 I-sPS NPs). The 131 I-sPS NPs showed low phototoxicity in normal tissues due to aggregation-caused quenching effect, but could self-produce reactive oxygen species in tumor sites upon disassembly. Upon intravenous injection, 131 I-sPS NPs showed great tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice and orthotopic VX2 liver tumor bearing rabbits. We believed 131 I-sPS NPs could expand the application of CR and provide an effective strategy for deep tumor theranostics.


Assuntos
Antineoplásicos/farmacologia , Clorofila/análogos & derivados , Neoplasias Hepáticas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Clorofila/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Radioisótopos do Iodo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Camundongos , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único
7.
Nanotechnology ; 32(39)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34157705

RESUMO

Recently, we have successfully realized the catalytic synthesis of nanodiamond (ND) by embedding the Fe catalyst into carbide under high stress, followed by chlorine-etching at atmospheric pressure. In this work, we selected Fe, Co and Ni as the catalyst, and TiC as the precursor, aiming at investigating the influence of the catalyst type on the synthesis of NDs. The results have shown that all the three catalysts can catalyze the synthesis of ND structure, where various types of NDs have been observed. Furthermore, the crystal type and plasticity of the catalyst may have an important influence on the type and size of the resultant ND. In the case of Fe and Ni as the catalyst, both of which have a face centered cubic crystal structure, the types of NDs obtained are mainly C-type and R-type but only a few H-type. However, when the Co with a close-packed hexagonal crystal structure is used as the catalyst, more H-type NDs can be catalytically synthesized. Moreover, more small-sized NDs have been catalytically synthesized by Co, which may be ascribed to the worse plasticity of Co by comparison to Fe and Ni.

8.
Tissue Eng Regen Med ; 18(4): 685-691, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34173219

RESUMO

BACKGROUND: Some scholars have found that dermal papilla spheroid-derived exosomes could promote the development of hair follicles. However, whether adipose-derived stem cell exosomes (ADSC-Exos) have a similar effect on hair growth has not been determined yet. Thus, the purpose of this article was to detect whether ADSC-Exos could promote hair regeneration. METHODS: Adipose-derived stem cells (ADSCs) were isolated from 6-week-old C57BL/6 mice. Then, ADSC-Exos were isolated from the ADSCs. Western blotting was used to detect specific exosome markers. The particle size and distribution of the exosomes were analyzed by NanoSight dynamic light scattering. A total of 12 nude mice were randomly divided into two groups (n = 6 each): the ADSC-Exos group and the control group. For the control group, a mixture of freshly isolated dermal cells (DCs) and epidermal cells (ECs) was grafted. For the ADSC-Exos group, a mixture of DCs, ECs, and 50 µg/ml of ADSC-Exos was grafted. Gross evaluation of the hair regeneration was carried out 2-3 weeks after the transplantation, and the graft site was harvested for histology at the third week. RESULTS: The existence of exosomes derived from ADSCs was evidenced by CD63, ALX1, and CD9 expression. Two or three weeks after the grafting, the number of regenerated hairs in the ADSC-Exos group was higher than that in the control group (p < 0.001). Histologically, the terminal hairs were remarkable in the ADSC-Exos group, whereas the hair follicles observed in the control group were comparatively immature. The ADSC-Exos group had a higher number of regenerated follicles than the control group (p < 0.001). In addition, we found that the skin tissues in the ADSC-Exos group had higher PDGF and vascular endothelial growth factor expressions and lower transforming growth factor beta 1 levels than those in the control group. CONCLUSION: Our results indicated that ADSC-Exos could promote in vivo hair follicle regeneration.


Assuntos
Exossomos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Regeneração , Células-Tronco , Fator A de Crescimento do Endotélio Vascular
9.
J Hazard Mater ; 415: 125692, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34088187

RESUMO

Mercury (Hg0) pollution poses a huge threat to human health and the environment due to its high toxicity, long persistence and bioaccumulation in the environment. Most of the traditional Hg0 adsorbents have a low reaction rate, high operating cost, especially poor resistance to SO2, which limited their practical application. In this work, nanosheet g-C3N4 was used as the support and modified by CuS to capture flue gas mercury. Take advantage of the large specific surface area of g-C3N4 to increase the BET of the composite and decrease the use of CuS. The effects of CuS loading, reaction temperature, and common components in the coal-fired flue gas on the mercury removal performance were studied respectively. The experimental outcomes showed that the 10CuS/g-C3N4 (10CuS/CN) reaches as high as almost 100% Hg0 removal efficiency under the temperature of 40-120 â„ƒ. Meanwhile the common components like SO2, NO, HCl and H2O have no obvious inhibition effects on Hg0 removal efficiency of the 10CuS/CN adsorbent. Sx2- and Cu2+ as the primary bonding sites shows a synergy effect on Hg0 removal. 10CuS/CN is a promising material for Hg0 removal under various flue gas conditions, which is expected to be a substitute for traditional adsorbents.

10.
Eur J Pharmacol ; 907: 174264, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34147476

RESUMO

Dengue fever is a common arbovirus disease, which has been spread to the entire tropical world. At present, effective drugs for the treatment of dengue fever have not yet appeared, and the dengue vaccines studied in various countries have also experienced severe adverse reactions. Thus it is urgent to find new chemicals against dengue virus. Now we found Sirtuins (SIRTs) were increased during dengue virus infection and tenovin-1, a SIRT1/2 inhibitor, showed an impressive antiviral ability in vitro. In BHK-21 cells, tenovin-1 inhibited the replication of DENV2 with an EC50 at 3.41 ± 1.10 µM, also inhibited other three types of dengue viruses with EC50 at 0.97 ± 1.11 µM, 1.81 ± 1.08 µM, 3.81 ± 1.34 µM respectively. Moreover, the cytopathic effect-induced DENV2 was largely improved by tenovin-1 treatment and the release of progeny viruses was inhibited by tenovin-1 treatment. At the same time, the viral protein level and mRNA level were decreased with tenovin-1 treatment after dengue virus infection. From the drug-addition assay, the tenovin-1 played its antiviral after viral infection, which indicated tenovin-1 was not a microbicide. Apart from its antiviral effect, tenovin-1 inhibited the inflammatory response caused by DENV2, reducing the release of inflammatory factors during viral infection. The antiviral effect of tenovin-1 was abrogated with SIRT agonist or SIRT2 knockdown treatment, which indicated the effect of tenovin-1 was on-target. In conclusion, tenovin-1 was proved to be a promising compound against flavivirus infection through SIRT2, which should be pay more attention for further study.

11.
Pharmacol Res ; 170: 105721, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34116207

RESUMO

Dengue virus (DENV) is the most prevalent arthropod-borne viral disease of humans and has a major impact on global public health. There is no clinically approved drugs for DENV infection. Since intracellular VEGFR2 is increased in DENV infected patients, we thus hypothesized that VEGFR2 participated DENV proliferation and its inhibitors could be served as antivirals against DENV. Actually our results showed that VEGFR2 was induced by DENV infection. Also the agonist of VEGFR2, VEGF-A, promoted DENV proliferation. Therefore, we screened the inhibitors of VEGFR2 and found that brivanib alaninate (brivanib) showed the best anti-DENV ability with the lowest cellular cytotoxicity. Mechanically, our results indicated VEGFR2 directly interacted with PTP1B to dephosphorylate AMPK to provide lipid environment for viral replication. However, this effect could be inhibited by brivanib, which significantly reversed the reduction of AMPK phosphorylation caused by DENV infection, thus improving the cellular lipid environment. Moreover, the antiviral effect of brivanib could be reversed by AMPK inhibitor, Compound C. In addition, oral administration of brivianib (20-50 mg/kg/day) clearly improved the survival rate of DENV2 infection, and this effect was abolished in accompanied with Compound C (10mg/kg/day). Collectively, our study disclosed the mechanism of VEGFR2 in DENV2 and evaluated the antiviral ability of brivanib, which deserved more attention for clinical usage in DENV infection.

12.
Exp Eye Res ; 209: 108629, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029595

RESUMO

The shortage of human donor corneas has raised important concerns about engineering of corneal endothelial cells (CECs) for clinical use. However, due to the limited proliferative capacity of human CECs, driving them into proliferation and regeneration may be difficult. Unlike human CECs, rabbit CECs have a marked proliferative capacity. To clarify the potential reason for this difference, we analysed the proteomes of four human corneal endothelium samples and four rabbit corneal endothelium samples with quantitative label-free proteomics and downstream analysis. We discovered that vitamin and selenocompound metabolism and some signaling pathways such as NF-kappa B signaling pathway differed between the samples. Moreover, TGFß, PITX2 and keratocan were distinctively expressed in rabbit samples, which might be associated with active proliferation in rabbit CECs. This study illustrates the proteomic differences between human and rabbit CECs and might promote CEC engineering strategies.


Assuntos
Doenças da Córnea/metabolismo , Transplante de Córnea/métodos , Endotélio Corneano/metabolismo , Proteínas de Homeodomínio/biossíntese , Proteoma/metabolismo , Proteômica/métodos , Fatores de Transcrição/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Idoso , Animais , Diferenciação Celular , Células Cultivadas , Doenças da Córnea/patologia , Doenças da Córnea/cirurgia , Modelos Animais de Doenças , Endotélio Corneano/citologia , Endotélio Corneano/transplante , Humanos , Masculino , Pessoa de Meia-Idade , Coelhos , Preservação de Tecido/métodos
13.
14.
J Invest Dermatol ; 141(5): 1254-1263.e6, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33069728

RESUMO

Genetic factors play a key role in the pathogenesis of autoimmune diseases, whereas the disease-causing variants remain largely unknown. Herein, we performed an exome-wide association study of systemic sclerosis in a Han Chinese population. In the discovery stage, 527 patients with systemic sclerosis and 5,024 controls were recruited and genotyped. In the validation study, an independent sample set of 479 patients and 1,096 controls were examined. In total, we found that four independent signals reached genome-wide significance. Among them, rs7574865 (Pcombined = 3.87 × 10-12) located within signal transducer and activator of transcription 4 gene was identified previously using samples of European ancestry. Additionally, another signal including three SNPs in linkage disequilibrium might be unreported susceptibility loci located in the epidermis differentiation complex region. Furthermore, two SNPs located within exon 3 of IGHM (rs45471499, Pcombined = 1.15 × 10-9) and upstream of LRP2BP (rs4317244, Pcombined = 4.17 × 10-8) were found. Moreover, rs4317244 was identified as an expression quantitative trait locus for LRP2BP that regulates tight junctions, cell cycle, and apoptosis in endothelial cell lines. Collectively, our results revealed three signals associated with systemic sclerosis in Han Chinese and suggested the importance of LRP2BP in systemic sclerosis pathogenesis. Given the limited sample size and discrepancies between previous results and our study, further studies in multiethnic populations are required for verification.

15.
Environ Pollut ; 268(Pt A): 115309, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152631

RESUMO

An experimentally induced three-dimensional petroleum seepage flume was used to investigate its migration in heterogeneous soil layers and a method for monitoring resistivity was adopted, under conditions of fluctuating water levels and rainfall. The corresponding mechanisms were then analyzed based on the resistivity characteristics and combined with three-dimensional inversion images. Finally, physical and chemical property analysis was conducted to verify the results of resistivity monitoring. The results demonstrated that: (1) In the process of natural oil leakage, the variation of soil resistivity presents a concave shape in the resistivity profile. Thus, oil migration exhibited the following patterns. At first, circular migration front was dominant in a vertical direction. Subsequently, after vertical migration was impeded, lateral migration was dominant. As the crude oil gradually accumulated, the migration front broke through the limitation of lithologic interface and continued vertically. (2) By comparing the two resistivity monitoring methods, namely the Wenner and Pole-pole methods, it was demonstrated that the inversion resistivity measured by Wenner method was closer to the true resistivity, and the resistivity variations were more distinguishable. (3) The resistivity inversion profile demonstrated that the low resistivity anomaly of the crude oil leakage area was related to the low water content of the soil layer in the test area. (4) Fluctuations in water level increased the diffusion range of crude oil beyond the original pollution source area, especially horizontally. (5) Percolation of rainfall caused the water level to rise, and the crude oil was evenly distributed in the soil layers above the capillary zone. (6) Through sample analysis and verification, it was demonstrated that the resistivity method can accurately and intuitively present the characteristics of crude oil migration. These results provide theoretical support for the rapid determination of the migration range and characteristics of crude oil in heterogeneous soil layers.


Assuntos
Petróleo , Poluentes do Solo , Difusão , Solo , Poluentes do Solo/análise , Água
16.
Mol Neurobiol ; 58(3): 1185-1195, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33099751

RESUMO

Leptin is an adipocytokine that is primarily secreted by white adipose tissue, and it contributes to the pathogenesis of neuropathic pain in collaboration with N-methyl-D-aspartate receptors (NMDARs). Functional NMDARs are a heteromeric complex that primarily comprise two NR1 subunits and two NR2 subunits. NR2A is preferentially located at synaptic sites, and NR2B is enriched at extrasynaptic sites. The roles of synaptic and extrasynaptic NMDARs in the contribution of leptin to neuropathic pain are not clear. The present study examined whether the important role of leptin in neuropathic pain was related to synaptic or extrasynaptic NMDARs. We used a rat model of spared nerve injury (SNI) and demonstrated that the intrathecal administration of the NR2A-selective antagonist NVP-AAM077 and the NR2B-selective antagonist Ro25-6981 prevented and reversed mechanical allodynia following SNI. Administration of exogenous leptin mimicked SNI-induced behavioral allodynia, which was also prevented by NVP-AAM077 and Ro25-6981. Mechanistic studies showed that leptin enhanced NR2B- but not NR2A-mediated currents in spinal lamina II neurons of naïve rats. Leptin also upregulated the expression of NR2B, which was blocked by the NR2B-selective antagonist Ro25-6981, in cultured dorsal root ganglion (DRG) neurons. Leptin enhanced neuronal nitric oxide synthase (nNOS) expression, which was also blocked by Ro25-6981, in cultured DRG cells. However, leptin did not change NR2A expression, and the NR2A-selective antagonist NVP-AAM077 had no effect on leptin-enhanced nNOS expression. Our data suggest an important cellular link between the spinal effects of leptin and the extrasynaptic NMDAR-nNOS-mediated cellular mechanism of neuropathic pain.


Assuntos
Leptina/efeitos adversos , Neuralgia/metabolismo , Neuralgia/patologia , Óxido Nítrico Sintase Tipo I/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , Animais , Comportamento Animal , Células Cultivadas , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Hiperalgesia/etiologia , Hiperalgesia/patologia , Masculino , Tecido Nervoso/lesões , Tecido Nervoso/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Sinapses/efeitos dos fármacos
17.
Cell Biochem Biophys ; 79(2): 231-238, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33125640

RESUMO

Skin fibrosis is one of the major features of scleroderma. WNT/ß-catenin signaling is associated with the progression of skin fibrosis. In this study, we aimed to determine the effect of icaritin (IT), a natural compound, on scleroderma-related skin fibrosis and its mechanisms. We found that IT could reduce the expression of COL1A1, COL1A2, COL3A1, CTGF, and α-SMA in human foreskin fibroblasts (HFF-1 cells), scleroderma skin fibroblasts (SSF cells), and TGF-ß-induced HFF-1 cells. Wnt/ß-catenin signaling was shown to be suppressed by IT. Additionally, IT activated AMPK signaling in HFF-1 cells. In conclusion, IT has an anti-skin fibrotic effect through activation of AMPK signaling and inhibition of WNT/ß-catenin signaling. Our findings indicate the potential role of IT in the treatment of scleroderma and provide novel insight for the selection of drug therapy for scleroderma.


Assuntos
Flavonoides/farmacologia , Escleroderma Sistêmico/patologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Actinas/genética , Actinas/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Escleroderma Sistêmico/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
18.
J Cosmet Dermatol ; 20(4): 1221-1230, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32888247

RESUMO

BACKGROUND: Platelet-rich plasma (PRP) is effective in the treatment of androgenetic alopecia (AGA). AIMS: The purpose of this study is to assess the effect of PRP on the proliferation of human follicle dermal papilla cells (HFDPCs), to observe the effect of PRP on the growth of hair follicles and hair shaft in vitro, to measure growth factors, and to evaluate the efficacy and safety of PRP injection. PATIENTS/METHODS: The effect of PRP on the proliferation of HFDPCs was observed. The length of hair follicle and hair shaft in vitro was measured. Then, the concentration of growth factors (EGF, FGF-2, FGF-7, IGF-1, HGF, PDGF-BB, and VEGF-A) was evaluated. Half-head injection of PRP was conducted to 10 males. Three treatments were conducted at 30-day intervals. Digital photographs were taken; hair diameter, hair density, unit density of hair follicles, and terminal hair/ vellus hair were analyzed. RESULTS: Platelet-rich plasma significantly promoted the proliferation of HFDPCs. Under the PRP culture, the hair follicle and hair shaft were grown, and the hair growth length on the 3rd and 6th days was greater than that of the control. PRP contained growth factors such as EGF, FGF-2, FGF-7, IGF-1, HGF, PDGF-B, and VEGF-A. Hair diameter, hair density, and unit hair follicle density on the PRP injection side peaked in the 6th month. The terminal hair/ vellus hair of the PRP injection side reached a peak in the 4th month. The average patient satisfaction during the entire treatment was 5.4 points (0-10 points). CONCLUSION: Platelet-rich plasma can promote hair growth. PRP injection is safe and effective for the treatment of AGA.


Assuntos
Alopecia , Plasma Rico em Plaquetas , Alopecia/terapia , Cabelo , Folículo Piloso , Humanos , Masculino , Projetos Piloto
19.
J Infect Dis ; 223(4): 686-698, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32663850

RESUMO

BACKGROUND: Interferon alfa (IFN-α) has been proved effective in treating chronic hepatitis B (CHB), owing to its ability to suppress hepatitis B surface antigen and hepatitis B virus (HBV) covalently closed circular DNA. However, the underlying mechanisms are unclear. METHODS: We investigated the antiviral activities of exosomes from responders and nonresponders to pegylated IFN-α (PegIFN-α) as well as the supernatants of IFN-α-treated macrophages derived from THP-1 (the human leukemia monocyte cell line). Then the expression profiles of exosomal microRNAs (miRNAs) were analyzed using miRNA sequencing. The luciferase reporter assay was used to locate the binding position of HBV genomic sequence targeted by the identified miRNA. RESULTS: Exosomes from PegIFN-α-treated patients, particularly responders, as well as the supernatants of IFN-α-treated macrophages exhibited anti-HBV activities, as manifested by the suppression of hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and covalently closed circular DNA levels in HBV-related cell lines. PegIFN-α treatment up-regulated exosomal hsa-miR-193a-5p, hsa-miR-25-5p, and hsa-miR-574-5p, which could partially inhibit HBV replication and transcription, and hsa-miR-574-5p reduced pregenomic RNA and polymerase messenger RNA levels by binding to the 2750-2757 position of the HBV genomic sequence. CONCLUSIONS: Exosomes can transfer IFN-α-related miRNAs from macrophages to HBV-infected hepatocytes, and they exhibit antiviral activities against HBV replication and expression.

20.
Protein Expr Purif ; 179: 105788, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33221504

RESUMO

MEF2D-fusions have recently been identified as one of the major oncogenic drivers in precursor B-cell acute lymphoblastic leukemia (B-ALL). More importantly, they are often associated with patients with poor prognosis in B-ALL. To have a better understanding of the pathogenic mechanism underpinning MEF2D-fusions-driven leukemogenesis, it's essential to uncover the related structure information. In this study, we expressed and purified the MEF2D N-terminal DNA binding domain. The recombinant protein was engineered by cloning the encoding gene into the expression vector pET-32 m. A series of chromatographic steps involving affinity, ion-exchange and gel-filtration chromatography were used to achieve a final purity of >95%. For the crystallization of the MEF2D-DNA complex, a double-stranded DNA encoding 5'-AACTATTTATAAGA-3' and 5'-TTCTTATAAATAGT-3' was used (Wu et al., 2010) [1]. The MEF2D-DNA crystal with the size of about 20 µm × 20 µm × 20 µm was obtained at a final concentration of 12 mg/ml at the reservoir condition containing 30% PEG1500. The X-ray examination showed that the MEF2D-DNA crystal diffracted to 4.5 Å resolution, and belonged to space group P1, with unit-cell parameters of a = 77.2 Å, b = 77.2 Å, c = 231.4 Å.


Assuntos
DNA , Proteínas Recombinantes , Sítios de Ligação/genética , Cromatografia Líquida , DNA/química , DNA/metabolismo , Humanos , Fatores de Transcrição MEF2/química , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/isolamento & purificação , Fatores de Transcrição MEF2/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Difração de Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...