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1.
Gels ; 7(4)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34842701

RESUMO

Poly(ethylene glycol) (PEG)-based synthetic hydrogels based on Michael-type addition reaction have been widely used for cell culture and tissue engineering. However, recent studies showed that these types of hydrogels were not homogenous as expected since micro domains generated due to the fast reaction kinetics. Here, we demonstrated a new kind of method to prepare homogenous poly(ethylene glycol) hydrogels based on Michael-type addition using the side chain amine-contained short peptides. By introducing such a kind of short peptides, the homogeneity of crosslinking and mechanical property of the hydrogels has been also significantly enhanced. The compressive mechanical and recovery properties of the homogeneous hydrogels prepared in the presence of side chain amine-contained short peptides were more reliable than those of inhomogeneous hydrogels while the excellent biocompatibility remained unchanged. Furthermore, the reaction rate and gelation kinetics of maleimide- and thiol-terminated PEG were proved to be significantly slowed down in the presence of the side chain amine-contained short peptides, thus leading to the improved homogeneity of the hydrogels. We anticipate that this new method can be widely applied to hydrogel preparation and modification based on Michael-type addition gelation.

2.
Nat Commun ; 12(1): 6327, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732696

RESUMO

Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as "living treatment agents" for cell therapy.

3.
J Bioenerg Biomembr ; 53(6): 665-677, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34731384

RESUMO

Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of the critically ill patient with high morbidity and mortality. Thus, the goal of this study was to investigate the role of circular RNA BCL2 Interacting Protein 3 Like (circ-BNIP3L) in the pathophysiological mechanism of SA-AKI. The SA-AKI cell model was established by using lipopolysaccharide (LPS)-induced HK-2 cells in vitro. Cell survival was analyzed using cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry and Western blot, respectively. Levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected using ELISA analysis. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were examined using commercial kits. Levels of genes and proteins were detected by qRT-PCR and Western blot. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target relationship between miR-370-3p and circ-BNIP3L or MYD88 (myeloid differentiation primary response 88). Circ-BNIP3L was highly expressed in SA-AKI patients and LPS-induced HK-2 cells. Silencing of circ-BNIP3L attenuated LPS-induced growth inhibition, inflammation, and oxidative stress in HK-2 cells. Mechanistically, circ-BNIP3L competitively bound to miR-370-3p to up-regulate the expression of its target MYD88. Moreover, miR-370-3p inhibition reversed the beneficial effects of circ-BNIP3L knockdown on LPS-stimulated HK-2 cells. Meanwhile, miR-370-3p overexpression abolished LPS-induced injury in HK-2 cells, which was counteracted by MYD88 up-regulation. Circ-BNIP3L knockdown alleviated LPS-induced renal tubular epithelial cell injury by miR-370-3p/MYD88 axis, opening up a completely new avenue for the treatment of sepsis-associated AKI.

4.
Biomed Res Int ; 2021: 5171086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34611527

RESUMO

As the main economic crop cultivated in the Yellow River Delta, winter jujube contains various nutrients. However, soil salinization and fungal diseases have affected the yield and quality of winter jujube. In order to use plant growth-promoting rhizobacteria (PGPR) to reduce these damages, the antagonistic bacteria CZ-6 isolated from the rhizosphere of wheat in saline soil was selected for experiment. Gene sequencing analysis identified CZ-6 as Bacillus amyloliquefaciens. In order to understand the salt tolerant and disease-resistant effects of CZ-6 strain, determination of related indicators of salt tolerance, pathogen antagonistic tests, and anti-fungal mechanism analyses was carried out. A pot experiment was conducted to evaluate the effect of CZ-6 inoculation on the rhizosphere microbial community of winter jujube. The salt tolerance test showed that CZ-6 strain can survive in a medium with a NaCl concentration of 10% and produces indole acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. Studies on the inhibition mechanism of pathogenic fungi show that CZ-6 can secrete cellulase, protease, and xylanase. Gas chromatography-mass spectrometry (GC-MS) analysis showed that CZ-6 can release volatile organic compounds (VOCs), including 2-heptanone and 2-nonanone. In addition, the strain can colonize the rhizosphere and migrate to the roots, stems, and leaves of winter jujube, which is essential for plant growth or defense against pathogens. Illumina MiSeq sequencing data indicated that, compared to the control, the abundance of salt-tolerant bacteria Tausonia in the CZ-6 strain treatment group was significantly increased, while the richness of Chaetomium and Gibberella pathogens was significantly reduced. Our research shows that CZ-6 has the potential as a biological control agent in saline soil. Plant damage and economic losses caused by pathogenic fungi and salt stress are expected to be alleviated by the addition of salt-tolerant antagonistic bacteria.

5.
Signal Transduct Target Ther ; 6(1): 361, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620840

RESUMO

Multiple myeloma (MM) is an incurable plasma cell malignancy in the bone marrow characterized by chromosome instability (CIN), which contributes to the acquisition of heterogeneity, along with MM progression, drug resistance, and relapse. In this study, we elucidated that the expression of BUB1B increased strikingly in MM patients and was closely correlated with poor outcomes. Overexpression of BUB1B facilitated cellular proliferation and induced drug resistance in vitro and in vivo, while genetic targeting BUB1B abrogated this effect. Mechanistic studies unveiled that enforced expression of BUB1B evoked CIN resulting in MM poor outcomes mainly through phosphorylating CEP170. Interestingly, we discovered the existence of circBUB1B_544aa containing the kinase catalytic center of BUB1B, which was translated by a circular RNA of BUB1B. The circBUB1B_544aa elevated in MM peripheral blood samples was closely associated with MM poor outcomes and played a synergistic effect with BUB1B on evoking CIN. In addition, MM cells could secrete circBUB1B_544aa and interfere the MM microenvironmental cells in the same manner as BUB1B full-length protein. Intriguingly, BUB1B siRNA, targeting the kinase catalytic center of both BUB1B and circBUB1B_544aa, significantly inhibited MM malignancy in vitro and in vivo. Collectively, BUB1B and circBUB1B_544aa are promising prognostic and therapeutic targets of MM.

6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 813-818, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622598

RESUMO

Objective: To segment images through an unsupervised method as an alternative to manual labeling. Methods: A total of 100 whole slide image (WSI) data of HE stained and Pap stained slides were selected as the research and test objects, including 70 breast slides, 20 lung slides and 10 thyroid slides. In order to ensure the diversity of data, the breast slides included those of normal tissue, inflammation and tumor, the lung slides were mainly neoplasms in the lower lobe, including those of inflammation and tumor, and the thyroid slides were of cells, all benign, obtained through fine needle aspiration. The maximum total magnification (original magnification) of each image was 400 times, and the file format was NDPI. Each WSI was manually labeled, and the labeled area of each WSI was more than 10 fields of vision. The labeled information was to be used for validity verification. An unsupervised image segmentation technique based on superpixel and fully convolution neural network algorithms was constructed and used to segment any region of interest (ROI) of unlabeled WSI. In comparison with the region adjacency graph merging method, the segmentation effect of the two methods was assessed with the under segmentation error, the boundary recall and the mean Intersection-over-Union, and the efficiency of the two methods was also compared. In the comparison of execution efficiency, the test process included the preprocessing time of superpixel, and excluded the time of loading the deep learning engine. Results: Unsupervised automatic segmentation was implemented for any ROI region of WSI according to the texture and color. The results of the breast slides, lung slides and thyroid slides showed slight differences, and multiple tests yielded stable results. However, the performance of this method in differentiating inflammation and tumor was average. The under-segmentation error, the boundary recall and the mean Intersection-over-Union were 19.10%, 82.06% and 45.06%, respectively. The under segmentation error, the boundary recall and the mean Intersection-over-Union for the region adjacency graph merging method were 21.52%, 78.39% and 44.81%, respectively. The average time consumption of the whole process was 0.27 s in GPU mode and 1.30 s in CPU mode. The average time consumption of the region adjacency graph merging method was 10.5 s in CPU mode because the method of region adjacency graph merging was not realized in the GPU mode. Conclusion: This method produced ideal pixel level labeling results through simple human-computer interaction, which could effectively reduce the cost of digital pathology slide data labeling. Compared with the region adjacency graph merging method, this method had better performance in processing image texture and had faster processing speed.


Assuntos
Algoritmos , Aprendizado de Máquina não Supervisionado , Mama , Humanos , Redes Neurais de Computação
7.
Int J Nanomedicine ; 16: 6217-6229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531654

RESUMO

Purpose: Osteoporosis, due to bone loss and structural deterioration, is a risk factor for dental implant failure, as it impedes initial stability and osseointegration. We aim to assess the effects of calcium phosphate polymer-induced liquid precursor (CaP-PILP) treatment, which significantly increases bone density and improves early implant osseointegration in ovariectomized rats. Methods: In this study, CaP-PILP was synthesized and characterized through TEM, FTIR and XRD. A rat model of osteoporosis was generated by ovariectomy. CaP-PILP or hydroxyapatite (HAP, negative control) was injected into the tibia, and the resulting changes in bone quality were determined. Further, implants were installed in the treated tibias, and implantation characteristics were assessed after 4 weeks. Results: The CaP-PILP group had superior bone repair. Importantly, CaP-PILP had excellent properties, similar to those of normal bone, in terms of implant osseointegration. In vivo experiment displayed that CaP-PILP group had better bone contact rate (65.97±3.176) than HAP and OVX groups. Meanwhile, a mound of mature and continuous new bone formed. Moreover, the values of BIC and BA showed no significant difference between the CaP-PILP group and the sham group. Conclusion: In summary, CaP-PILP is a promising material for application in poor-quality bones to improve implant success rates in patients with osteoporosis. This research provides new perspectives on the application of nano-apatite materials in bone repair.


Assuntos
Implantes Dentários , Osseointegração , Animais , Densidade Óssea , Durapatita , Feminino , Humanos , Ovariectomia , Polímeros , Ratos , Tíbia , Titânio
8.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4774-4781, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581088

RESUMO

Indolealkylamines(IAAs) are the main hydrophilic substances in toad skin, mainly including free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine. In this study, the LPS-activated neutrophils were used to investigate the structure-activity relationship and anti-inflammatory mechanism of the above-mentioned five monomers from the toad skin in vitro. The neutrophils were divided into the control group, model group(1 µg·mL~(-1) LPS), positive drug group(100 µg·mL~(-1) indometacin), as well as the low-(50 µg·mL~(-1)), medium-(100 µg·mL~(-1)) and high-dose(200 µg·mL~(-1)) free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine groups. The levels of IL-6, TNF-α and IL-1ß in the neutrophil supernatant of each group was measured by enzyme-linked immunosorbent assay(ELISA) after LPS stimulation, followed by the detection of apoptosis in each group after Annexin V/PI staining. The protein expression levels of caspase-3, Bax, Bcl-2, beclin1, LC3-I, and LC3-Ⅱ were assayed by Western blot. The results showed that IAAs reduced the excessive secretion of inflammatory cytokines caused by LPS compared with the model group. Besides, the activity of each free IAAs(N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine and dehydrobufotenine), especially bufotenine, was stronger than that of the binding bufothionine. As revealed by Annexin V/PI staining, LPS delayed the early apoptosis of neutrophils compared with the control group, while bufotenine promoted the apoptosis of neutrophils in a dose-dependent manner, which might be related to the elevated expression of apoptosis-related protein Bax/Bcl-2. In addition, LPS activated the autophagy pathways in neutrophils. This study confirmed the efficacy of IAAs in reducing the secretion of inflammatory cytokines in neutrophils induced by LPS for the first time. For instance, bufotenine exerts the anti-inflammatory effect possibly by inducing the apoptosis of neutrophils.


Assuntos
Lipopolissacarídeos , Neutrófilos , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Bufonidae , Lipopolissacarídeos/toxicidade , Pele
9.
Biomed Pharmacother ; 143: 112160, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560546

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Bu-Shen-Tong-Du prescription (BSP) has traditionally been used in to treat RA but its underlying mechanisms remain unclear. In this study, we explored the potential mechanisms of BSP in collagen-induced arthritis (CIA) rats, a classic animal model of RA. We employed an integrated pharmacology approach in combination with network pharmacology, 1H-nuclear magnetic resonance (NMR) metabolomics, and biochemical analyses to determine the mechanisms of BSP for treating RA. We found that BSP can regulate immunity and inflammation by decreasing the spleen index; inhibiting hyperplasia of the white pulp; reducing the levels of IL-1ß, IL-6, IL-17A, and IFN-γ; and increasing the levels of IL-10 in the serum. Network pharmacology was utilized to predict related signal transduction pathways of BSP in RA treatment. 1H NMR metabolomics of the serum confirmed that BSP regulated energy metabolism and amino acid metabolism. Finally, we validated the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway using immunohistochemical methods, which demonstrated that BSP controlled RA-induced inflammation by inhibiting the TLR4/NF-κB signaling pathway. These results confirm the therapeutic effect of BSP in a CIA rat model, which is exerted via the inhibition of the inflammation and the improvement of the immune function, balancing energy metabolism and amino acid metabolism, and inhibiting the TLR4/NF-κB signaling pathway. This study provides an experimental basis for using BSP as a combinatorial drug to inhibit inflammation and regulate immunity in the treatment of RA.

10.
Brain Imaging Behav ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415492

RESUMO

Electroacupuncture (EA) is a safe and effective method for treating obesity. However, how it modulates reward-related brain activity/functional connectivity and gut hormones remains unclear. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and resting-state functional connectivity (RSFC) to investigate EA induced changes in resting-state activity and RSFC in reward-related regions and its association with gut hormones in overweight/obese subjects who received real (n = 20) and Sham (n = 15) stimulation. Results showed reduced leptin levels was positively correlated with reduced body mass index (BMI) and negatively correlated with increased cognitive-control as measured with Three-Factor-Eating-Questionnaire (TFEQ). Significant time effects on RSFC between dorsal caudate (DC) and precuneus were due to significant increased RSFC strength in both EA and Sham groups. In addition, increased RSFC of DC-precuneus was negatively correlated with reduced BMI and leptin levels in the EA group. Mediation analysis showed that the relationship between increased DC-precuneus RSFC strength and reduced BMI was mediated by reduced leptin levels. These findings reflect the association between EA-induced brain reward-related RSFC and leptin levels, and decreased leptin levels mediated altered DC-precuneus RSFC strength and consequent weight-loss, suggesting the potential role of EA in reducing weight and appetite.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34342825

RESUMO

Reservoir water is the most important freshwater resource for many cities, especially in densely populated humid subtropical areas. Economic growth, population increase, and urbanization have been putting reservoir water of Shenzhen (China), a humid subtropical city, under severe threat of eutrophication and water supply shortage. In this study, we focused on an upstream reservoir of Shenzhen and established a 3-dimensional hydrodynamic-ecological model to investigate the water dynamics and nutrient budget. Tributaries to the reservoir were identified as the greatest contributors to nitrogen and phosphorus loads. Zones with weak flows and high nutrient concentration have high risks of causing blooms. Several mitigation measures were proposed, including improving flow by adding additional water exit locations in the reservoir, reducing nutrients in tributaries, and enhancing algal predation, and were evaluated with the established model. The strategies combining hydrodynamic improvement and phosphorus reduction were suggested to decision makers and government managers for short-term management. However, for future water safety, excessive nitrogen is a potential danger. This study provides a modeling framework that can be applied to anthropogenic-influenced reservoirs elsewhere.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 693-697, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323051

RESUMO

Objective: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results. Methods: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient ( ICC) was used to evaluate the correlation. Results: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal. Conclusion: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.


Assuntos
Neoplasias da Mama , Inteligência Artificial , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Antígeno Ki-67 , Microscopia , Reprodutibilidade dos Testes
13.
Dalton Trans ; 50(28): 9914-9922, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34223568

RESUMO

Luminescent ß-diketone-based lanthanide complexes have been well explored as chemical sensor materials for biomedicine applications. Herein, three mononuclear Eu3+ complexes based on bis-ß-diketone ligands (L1, L2 and L3) that can reduce luminescence quenching caused by water were developed. The ligands feature two ß-diketone units covalently bound at the 1,8-position of the derivatized anthracene (modified with tetracyanoethylene, TCNE). X-ray crystallographic analysis reveals that their self-assemblies with Ln3+ ions in a 2 : 1 stoichiometric ratio form mononuclear anion complexes, [EuL2]-, in which two ligands coordinate to the metal center in a mutually orthogonal manner. This kind of arrangement together with the bulge of TCNE from the anthracene plane well protected the complexes from the quenching effects of water molecules in the second coordination. The photophysical measurements showed that the complexes not only had high luminescence quantum yields (QYs, up to 50-67%) but also presented excellent water-quenching resistant capability.

14.
Pharm Biol ; 59(1): 860-867, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34214019

RESUMO

CONTEXT: Schizandrin A (Sch A) is a major phytochemical from Schisandra chinensis (Turcz.) Baill. (Schisandraceae), which exerts a neuroprotective effect in Alzheimer's disease (AD). OBJECTIVE: To investigate the mechanism of Sch A in AD. MATERIALS AND METHODS: AD group: APP/PS1 transgenic mice served as AD models; AD + SCH group: APP/PS1 received 2 mg/kg Sch A by intragastric administration; WT: C57BL/6 mice were used as control. For in vitro assay, mouse microglial BV2 cells were treated with 0.5 µg/mL lipopolysaccharide or combined with 10 µmol/L Sch A for 24 h. The cognitive function and apoptosis in the mice was estimated. Microglial polarisation in the mice and cells was analysed. RESULTS: Sch A treatment effectively improved spatial learning and memory ability and suppressed apoptosis in the brain tissues of APP/PS1 mice. APP/PS1 mice exhibited an increase in the levels of Aß1-42 (2367.9 ± 431.1 pg/mg) and Aß1-40 (1753.3 ± 253.4 pg/mg), which was abolished by Sch A treatment. Moreover, Sch A treatment repressed the proportions of iNOS+/Iba-1+ cells and IL-6 expression, while enhanced the proportions of Arg-1+/Iba-1+ cells and IL-10 expression in APP/PS1 mice. In vitro, Sch A treatment reduced the proportions of CD16/32+ cells, iNOS expression and IL-6 levels (25.7 ± 5.3 pg/mL) repressed M1 polarisation, and enhanced the proportions of CD206 cells, Arg-1 expression and IL-10 levels (75.9 ± 12.8 pg/mL) in BV2 cells. CONCLUSIONS: This research confirms the neuroprotective effect of Sch A in AD, suggesting that Sch A may become a potential anti-AD agent.

15.
Front Aging Neurosci ; 13: 658376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168550

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by the complex interaction of multiple mechanisms. Recent studies examining the effect of high-fat diet (HFD) on the AD phenotype have demonstrated a significant influence on both inflammation and cognition. However, different studies on the effect of high-fat diet on AD pathology have reported conflicting conclusions. To explore the involvement of HFD in AD, we investigated phenotypic and metabolic changes in an AD mouse model in response to HFD. The results indicated there was no significant effect on Aß levels or contextual memory due to HFD treatment. Of note, HFD did moderate neuroinflammation, despite spurring inflammation and increasing cholesterol levels in the periphery. In addition, diet affected gut microbiota symbiosis, altering the production of bacterial metabolites. HFD created a favorable microenvironment for bile acid alteration and arachidonic acid metabolism in APP/PS1 mice, which may be related to the observed improvement in LXR/PPAR expression. Our previous research demonstrated that Huanglian Jiedu decoction (HLJDD) significantly ameliorated impaired learning and memory. Furthermore, HLJDD may globally suppress inflammation and lipid accumulation to relieve cognitive impairment after HFD intervention. It was difficult to define the effect of HFD on AD progression because the results were influenced by confounding factors and biases. Although there was still obvious damage in AD mice treated with HFD, there was no deterioration and there was even a slight remission of neuroinflammation. Moreover, HLJDD represents a potential AD drug based on its anti-inflammatory and lipid-lowering effects.

16.
Diving Hyperb Med ; 51(2): 134-139, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34157727

RESUMO

INTRODUCTION: Exposure to very high oxygen partial pressure may cause central nervous system oxygen toxicity (CNS-OT). The role of necroptosis in the pathogenesis of CNS-OT is still unclear. METHODS: In experiment one, male C57BL/6 mice in the oxygen toxicity (OT) group (n = 5) and necrostatin-1 (Nec-1; a necroptosis inhibitor) (1.5 mg·kg-1, intraperitoneal) group (n = 5) were exposed to pure oxygen at 600 kPa, and the latency to tonic-clonic seizure was recorded. In experiment two, mice were divided into three groups: control group (n = 11), OT group (n = 12) and Nec-1 group (n = 12). Nec-1 was intraperitoneally administered 30 min before oxygen exposure. Mice in the OT group and Nec-1 group were exposed to pure oxygen at 400 kPa for 30 min, and then sacrificed; the brain was harvested for the assessment of inflammation, oxidative stress and necroptosis. RESULTS: Experiment one. Nec-1 pre-treatment significantly prolonged the latency to seizure (245 [SD 18] seconds in the OT group versus 336 (34) seconds in the Nec-1 group). Experiment two. Nec-1 pre-treatment markedly reduced inflammatory cytokines and inhibited cerebral necroptosis, but failed to significantly suppress cerebral oxidative stress. CONCLUSIONS: These findings indicate necroptosis is involved in the pathogenesis of CNS-OT, and inhibition of necroptosis may prolong seizure latency, but the specific mechanisms should be investigated further.


Assuntos
Oxigênio , Convulsões , Animais , Apoptose , Imidazóis , Indóis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pressão Parcial , Convulsões/induzido quimicamente
17.
J Sex Marital Ther ; 47(6): 571-590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33988489

RESUMO

Sexual objectification is a common pornographic theme. Research shows that sexual objectification leads to the expression of aggressive attitudes and behaviors toward women. Based on a survey study of 320 male participants, this study re-conceptualizes sexual objectification in terms of two forms of dehumanization. Evidence suggests men's pornography use is positively associated with both forms, but mechanistic dehumanization of women is more associated with aggressive attitudes while animalistic dehumanization is more associated with aggressive behaviors. Findings indicate how objectifying pornography use may relate to aggressive attitudes and behaviors and inform the future education campaigns and interventions to reduce sexual aggression.


Assuntos
Agressão , Literatura Erótica , Atitude , Desumanização , Feminino , Humanos , Masculino , Comportamento Sexual
18.
Front Cell Dev Biol ; 9: 675939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968945

RESUMO

The potential to overcome resistance to proteasome inhibitors is greatly related with ubiquitin-proteasome system during multiple myeloma (MM) treatment process. The constitutive photomorphogenic 1 (RFWD2), referred to an E3 ubiquitin ligase, has been identified as an oncogene in multiple cancers, yet important questions on the role of RFWD2 in MM biology and treatment remain unclear. Here we demonstrated that MM patients with elevated RFWD2 expression achieved adverse outcome and drug resistance by analyzing gene expression profiling. Moreover, we proved that RFWD2 participated in the process of cell cycle, cell growth and death in MM by mass spectrometry analysis. In vitro study indicated that inducible knockdown of RFWD2 hindered cellular growth and triggered apoptosis in MM cells. Mechanism study revealed that RFWD2 controlled MM cellular proliferation via regulating the degradation of P27 rather than P53. Further exploration unveiled that RFWD2 meditated P27 ubiquitination via interacting with RCHY1, which served as an E3 ubiquitin ligase of P27. Finally, in vivo study illustrated that blocking RFWD2 in BTZ-resistant MM cells overcame the drug resistance in a myeloma xenograft mouse model. Taken together, these findings provide compelling evidence for prompting that targeting RFWD2 may be an effective strategy to inhibit cellular proliferation and overcome drug resistance to proteasome inhibitor in MM.

19.
Front Pharmacol ; 12: 616318, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995016

RESUMO

"Shanghuo" ("excessive internal heat") is caused by exuberant endogenous fire, which does not have a comprehensive and systematic traditional Chinese medicine theory. In previous study, we had evaluated the therapeutic effect of Huanglian Jiedu Decoction (HLJDD) (granule) on patients with "Shanghuo", however, the specific mechanism was not clear, which need further exploration. To explain its intervention mechanism, we select 57 patients with oral diseases caused by "Shanghuo" and 20 health volunteers to divide into oral disease group, HLJDD intervention group and healthy control group. Firstly, biochemical indicators before and after HLJDD intervention are detected, such as inflammatory factors, oxidative stress factors and energy metabolism factors. The results exhibit that HLJDD significantly decreases indicators succinic acid (p < 0.001); tumor necrosis factor-alpha, adenosine triphosphate, citric acid (p < 0.01); interleukin-8 (IL-8), 4-hydroxynonenal, pyruvic acid, lactate dehydrogenase (p < 0.05). The levels of glucocorticoid, adrenocorticotropic hormone (p < 0.01); lactic acid, IL-4, IL-10 (p < 0.05) significantly increase after HLJDD intervention. In addition, we adopt multi-omics analysis approach to investigate the potential biomarkers. Nontargeted metabolomics demonstrate that the levels of 7 differential metabolites approach that in the healthy control group after HLJDD intervention, which are correlated with histidine metabolism, beta-alanine metabolism and sphingolipid metabolism through metabolic pathway analysis. Targeted lipidomics results and receiver operating characteristic curve analysis show that 13 differential lipids are identified in the three groups mainly focuse on lysophosphatidylcholines, lysophosphatidylethanolamines. Finally, the network associations of those differential biomarkers reveal the regulation of adenosine triphosphate and tricarboxylic acid cycle play essential role in the therapeutic effect mechanism of HLJDD in "Shanghuo". The study has laid the foundation for further revealing the mechanism and finding clinical biomarkers related to "Shanghuo".

20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(1): 111-121, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33899435

RESUMO

The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA in vitro to avoid wasting time and resource costs before animal experiments. In addition, how to efficiently obtain positive gene editing monoclonal cells is a difficult problem to be solved. In this study, a rapid sgRNA screening method targeting the pig genome was established and we rapidly obtained Fah gene edited cells, laying a foundation for the subsequent production of Fah knockout pigs as human hepatocyte bioreactor. At the same time, the method of obtaining monoclonal cells using pattern microarray culture technology was explored.


Assuntos
Sistemas CRISPR-Cas , RNA Guia , Animais , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Edição de Genes , RNA Guia/genética , Suínos
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