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1.
Artigo em Inglês | MEDLINE | ID: mdl-34599547

RESUMO

Disclosed herein is the first carbene-organocatalyzed asymmetric addition of phosphine nucleophiles to the in situ generated α,ß-unsaturated acyl azolium intermediates. Our reaction enantioselectively constructs carbon-phosphine bonds and prepares chiral phosphines with high optical purities. The phosphine products are suitable for transforming to chiral ligands or catalysts with applications in asymmetric catalysis. The diarylalkyl or trialkyl phosphine products from our catalytic reactions, air-sensitive and reactive in nature, can be trapped (and stored) in their sulfur-oxidized form for operational simplicities.

2.
Reprod Biol Endocrinol ; 19(1): 133, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481496

RESUMO

BACKGROUND: In-vitro-grow (IVG) of preantral follicles is essential for female fertility preservation, while practical approach for improvement is far from being explored. Studies have indicated that neurotrophin-4 (NT-4) is preferentially expressed in human preantral follicles and may be crucial to preantral follicle growth. METHODS: We observed the location and expression of Tropomyosin-related kinase B (TRKB) in human and mouse ovaries with immunofluorescence and Western blot, and the relation between oocyte maturation and NT-4 level in follicular fluid (FF). Mice model was applied to investigate the effect of NT-4 on preantral follicle IVG. Single-cell RNA sequencing of oocyte combined with cell-specific network analysis was conducted to uncover the underlying mechanism of effect. RESULTS: We reported the dynamic location of TRKB in human and mouse ovaries, and a positive relationship between human oocyte maturation and NT-4 level in FF. Improving effect of NT-4 was observed on mice preantral follicle IVG, including follicle development and oocyte maturation. Transcriptome analysis showed that the reparative effect of NT-4 on oocyte maturation might be mediated by regulation of PI3K-Akt signaling and subsequent organization of F-actin. Suppression of advanced stimulated complement system in granulosa cells might contribute to the improvement. Cell-specific network analysis revealed NT-4 may recover the inflammation damage induced by abnormal lipid metabolism in IVG. CONCLUSIONS: Our data suggest that NT-4 is involved in ovarian physiology and may improve the efficiency of preantral follicle IVG for fertility preservation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34465138

RESUMO

URFs are more likely developed among HIV-1 infections through MSM because of multiple subtypes co-circulation. In this study, two novel URFs deriving from two HIV-positive subjects (HB010014, HB010063) were identified in Shijiazhuang, Hebei province, China, and two sequences formed a distinct monophyletic cluster. The further recombination analysis showed that of two new URFs were consisted of CRF01_AE and CRF07_BC. The subregion phylogenetic analysis indicated that CRF01_AE segments were traced back to cluster 4 of CRF01_AE strains, which were prevalent among HIV-1 infections through MSM in China. New URFs being developing gradually and spreading released that more and more novel recombinant strains of HIV-1 could be developed, which means that the past prevention strategies need to be adjusted.

4.
Front Immunol ; 12: 723585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489974

RESUMO

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , COVID-19/classificação , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
5.
Neurogastroenterol Motil ; : e14249, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536258

RESUMO

BACKGROUND/AIMS: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients. METHODS: Forty-two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham-TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF-α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry. KEY RESULTS: Compared with Sham-TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham-TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF-α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05). CONCLUSIONS & INFERENCES: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF-α, probably mediated via the autonomic and ghrelin mechanisms.

6.
Mar Biotechnol (NY) ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480240

RESUMO

Epidermal mucus is an important barrier and regulating mediator in fish. MicroRNAs (miRNAs) are proved to be involved in various biological processes, also as promising biomarkers for disease diagnosis. Vibrio harveyi has long been a noticeable bacterial pathogen in Cynoglossus semilaevis aquaculture. To find the evidence whether there are indicating miRNAs in mucus and whether the miRNAs are related to infections caused by V. harveyi, miRNA profiles of mucus from V. harveyi infected fish and healthy controls were screened by small RNA sequencing and verified by quantitative real-time PCR. This is the first report about miRNA profiling of flatfish mucus, aiming at illustrating the pathogenesis of V. harveyi caused infection and developing disease-related biomarkers. The results revealed significant differences in expression levels of some miRNAs between infected fish and healthy ones. Three hundred differentially expressed miRNAs were obtained after filtering through FC > 2 or FC < 0.5 and most of the differential miRNAs were downregulated. After verification through qRT-PCR, four unique miRNAs, dre-miR-451, dre-miR-184, dre-miR-205-5p > ssa-miR-205b-5p, and dre-miR-181a-5p > ssa-miR-181a-5p, were identified as V. harveyi infection-related signatures, consistent with sequencing trend. The expression levels of these four miRNAs in the infected fish were all significantly lower than controls. These miRNAs in mucus could be used to differentiate diseased and healthy fish in a non-invasive way with practical value for large-scale disease screening. They also provided new insights into the mechanism underlying the bacterial infections in fish.

7.
Hum Mutat ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550612

RESUMO

Mutations of fibrillin-1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as "type I fibrillinopathy". However, few genotype-phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel-based next-generation sequencing, complemented with multiplex ligation-dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C-terminal region had a higher incidence of posterior staphyloma than those in the middle and N-terminal regions. Mutations in the TGF-ß-regulating sequence had larger horizontal corneal diameters (white-to-white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C-terminal region or TGF-ß regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype-phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies.

8.
J BUON ; 26(4): 1653-1658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34565032

RESUMO

PURPOSE: To investigate the etiologies of remarkably elevated serum levels of CA 19-9. METHODS: During January 2014 to June 2020 patients with CA 19-9>1000 U/ml were included. The frequencies of distant metastases for malignant patients and serum levels of carbohydrate embryonic antigen (CEA) and carbohydrate antigen 125 (CA 125) were analyzed. RESULTS: Of the 125 patients included, 113 (90.4%) were diagnosed with malignancy, 100 (80%) with digestive cancer and only 36 (28.8%) with pancreatic cancer (PC). In patients with malignancy, 75 (66.3%) had distant metastasis and 60 (53.1%) had liver metastasis. The median levels of CEA and CA 125 in patients with malignant disease were significantly higher than in patients with benign disease (19.05 ng/ml versus 3.16 ng/ml, p=0.01; 83.32 U/ml versus 18.35 U/ml, p=0.01, respectively). CONCLUSION: CA 19-9>1000U/ml indicated a high probability of having malignant disease, especially digestive cancer, but not always PC. Patients with malignant disease had high proportion of distant metastasis, mostly in the liver. Combined tests of CEA and CA 125 had potential role in distinguishing between benign and malignant diseases.

9.
Med Sci Monit ; 27: e930421, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415897

RESUMO

BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

10.
J Transl Med ; 19(1): 347, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389031

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. METHODS: TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. RESULTS: We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. CONCLUSIONS: Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Linhagem Celular Tumoral , Humanos , Ferro , Camundongos , Macrófagos Associados a Tumor
11.
Comput Biol Chem ; 94: 107517, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34456161

RESUMO

In recent years, the level of interest has been increased in developing the DNA-repair inhibitors, to enhance the cytotoxic effects in the treatment of cancers. Polynucleotide kinase/phosphatase (PNKP) is a critical human DNA repair enzyme that repairs DNA strand breaks by catalyzing the restoration of 5'-phosphate and 3'-hydroxyl termini that are required for subsequent processing by DNA ligases and polymerases. PNKP is the only protein that repairs the 3'-hydroxyl group and 5'-phosphate group, which depicts PNKP as a potential therapeutic target. Besides, PNKP is the only DNA-repair enzyme that contains the 5'-kinase activity, therefore, targeting this kinase domain would motivate the development of novel PNKP-specific inhibitors. However, there are neither crystal structures of human PNKP nor the kinase inhibitors reported so far. Thus, in this present study, a sequential molecular docking-based virtual screening with multiple PNKP conformations integrating homology modeling, molecular dynamics simulation, and binding free energy calculation was developed to discover novel PNKP kinase inhibitors, and the top-scored molecule was finally submitted to molecular dynamics simulation to reveal the binding mechanism between the inhibitor and PNKP. Taken together, the current study could provide some guidance for the molecular docking based-virtual screening of novel PNKP kinase inhibitors.

12.
Biomed Res Int ; 2021: 6693889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222481

RESUMO

Background: Healthcare-associated infection (HAI) is a serious threat to the safety of patients worldwide. The prevalence survey is widely used to explore and study the characteristics of HAI. However, the annual continuous prevalence survey of hospital-acquired infections has not been reported so far. Aim: This study is aimed at examining the occurrence and development trend of HAIs dynamically and accurately. Methods: An annual continuous HAI prevalence survey based on the real-time monitoring system was conducted in representative hospitals from different regions in Shandong in China. Findings. A total of 64 hospitals participated in the survey, and 2,741,433 patients were monitored in 2018. The highest prevalence of HAIs in Shandong was 3.83% (February 15), the lowest was 1.85% (February 28), and the average was 2.45%. The percentile distribution of prevalence of HAIs in this study was as follows: P10, 2.23%; P25, 2.31%; P50, 2.41%; P75, 2.55%; and P90, 2.73%. Conclusion: This study dynamically and accurately showed the occurrence and development trend of HAIs in Shandong in 2018. The results of this study can be used as a reference for the HAI prevalence survey in various medical institutions in Shandong and provide the basis for the regional HAI prevention and control strategy.

13.
J Cell Mol Med ; 25(17): 8558-8566, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34322990

RESUMO

Mesenchymal stem cells (MSCs) have been shown as an effective medicinal means to treat bronchopulmonary dysplasia (BPD). The widely used MSCs were from Wharton's jelly of umbilical cord (UC-MSCs) and bone marrow (BM-MSCs). Amniotic fluid MSCs (AF-MSCs) may be produced before an individual is born to treat foetal diseases by autoplastic transplantation. We evaluated intratracheal (IT) MSCs as an approach to treat an hyperoxia-induced BPD animal model and compared the therapeutic effects between AF-, UC- and BM-MSCs. A BPD animal model was generated by exposing newborn rats to 95% O2 . The continued stress lasted 21 days, and the treatment of IT MSCs was conducted for 4 days. The therapeutic effects were analysed, including lung histology, level of inflammatory cytokines, cell death ratio and state of angiogenesis, by sacrificing the experimental animal at day 21. The lasting hyperoxia stress induced BPD similar to the biological phenotype. The treatment of IT MSCs was safe without deaths and normal organ histopathology. Specifically, the treatment was effective by inhibiting the alveolar dilatation, reducing inflammatory cytokines, inducing angiogenesis and lowering the cell death ratio. AF-MSCs had better therapeutic effects compared with UC-MSCs in relieving the pulmonary alveoli histological changes and promoting neovascularization, and UC-MSCs had the best immunosuppressive effect in plasma and lung lysis compared with AF-MSCs and BM-MSCs. This study demonstrated the therapeutic effects of AF-, UC- and BM-MSCs in BPD model. Superior treatment effect was provided by antenatal MSCs compared to BM-MSC in a statistical comparison.

14.
Biomed Res Int ; 2021: 5698483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195270

RESUMO

Background: This study investigated and analyzed the current situation of sharp injuries among health care workers (HCWs) in China's Shandong Province. Methods: By means of questionnaire survey, the incidence of sharp injuries among HCWs from 36 hospitals in China's Shandong Province in October 2019 was investigated, and the results of this survey were compared with those of October 2012. Results: A total of 48165 HCWs were investigated. 549 cases of sharp injuries occurred. The incidence of sharp injuries was 1.14%, which was significantly lower than that in October 2012 (9.71%). In the occupational distribution of sharp injuries among HCWs, the proportion of nurses was 58.65%, doctors 23.32%, and interns 12.02%. Among the distribution of sharp injury departments, general wards, operating rooms, intensive care units, disinfection supply centers, and outpatient clinics were the high-incidence sites of occupational exposure among HCWs. The main instruments causing sharp injuries in HCWs were syringes, scalp steel needles, surgical suture needles, vacuum blood collection needles, and glass slides. Drug administration, double-handed loop needle cap, blood extraction, surgical suture needle, and arteriovenous needle extraction were high-risk operations causing sharp instrument injuries in HCWs. Conclusion: The incidence of sharp injuries among HCWs from 36 hospitals in Shandong Province in October 2019 was significantly lower than that in October 2012. Sharp injuries were a common type of occupational exposure for HCWs. The occurrence of sharp injuries should be effectively reduced by changing wrong habitual behavior and implementing standard protective measures.

15.
Sensors (Basel) ; 21(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210041

RESUMO

The phase-to-height imaging model, as a three-dimensional (3D) measurement technology, has been commonly applied in fringe projection to assist surface profile measurement, where the efficient and accurate calculation of phase plays a critical role in precise imaging. To deal with multiple extra coded patterns and 2π jump error caused to the existing absolute phase demodulation methods, a novel method of phase demodulation is proposed based on dual variable-frequency (VF) coded patterns. In this paper, the frequency of coded fringe is defined as the number of coded fringes within a single sinusoidal fringe period. First, the effective wrapped phase (EWP) as calculated using the four-step phase shifting method was split into the wrapped phase region with complete period and the wrapped phase region without complete period. Second, the fringe orders in wrapped phase region with complete period were decoded according to the frequency of the VF coded fringes and the continuous characteristic of the fringe order. Notably, the sampling frequency of fast Fourier transform (FFT) was determined by the length of the decoding interval and can be adjusted automatically with the variation in height of the object. Third, the fringe orders in wrapped phase region without complete period were decoded depending on the consistency of fringe orders in the connected region of wrapped phase. Last, phase demodulation was performed. The experimental results were obtained to confirm the effectiveness of the proposed method in the phase demodulation of both discontinuous objects and highly abrupt objects.


Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador , Análise de Fourier , Imageamento Tridimensional
16.
J Ethnopharmacol ; 280: 114415, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34271113

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Angelica sinensis is widely used in traditional Chinese Medicine for relieving gynecological discomforts among the women population. However, its hormone-like effects have raised great attention on whether it is appropriate to use in breast cancer (BC) patients. Hence, this study aimed to investigate the tumorigenic effect of aqueous root extract of Angelica sinensis (AS) on estrogen receptor (ER)-positive BC growth through ER-induced stemness in-vitro and in-vivo. MATERIALS AND METHODS: The chemical composition of the AS was characterized by HPLC. Cell viability was detected by MTS assay. The in-vivo effect of AS was investigated by xenograft model, immunohistochemistry, histology, Western blot, and self-renewal ability assay. Target verification was used by shRNA construction and transfection. Mammosphere formation assay was performed by flow cytometry. RESULTS: AS significantly promoted the proliferation of MCF-7 cells and inhibited the growth of MDA-MB-231 cells. AS significantly induced tumor growth (2.5 mg/kg) in xenograft models and however tamoxifen treatment significantly suppressed the AS-induced tumor growth. AS induced ERα expression in both in-vivo and in-vitro and promoted cancer stem cell activity in ER-positive BC. CONCLUSION: AS shows the tumorigenic potential on ER-positive BC growth through ERα induced stemness, suggesting that the usage of AS is not recommended for BC in terms of safety measures.

17.
Mol Divers ; 25(3): 1271-1282, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34160714

RESUMO

Nowadays, more and more attention has been attracted to develop selective PI3Kγ inhibitors, but the unique structural features of PI3Kγ protein make it a very big challenge. In the present study, a virtual screening strategy based on machine learning with multiple PI3Kγ protein structures was developed to screen novel PI3Kγ inhibitors. First, six mainstream docking programs were chosen to evaluate their scoring power and screening power; CDOCKER and Glide show satisfactory reliability and accuracy against the PI3Kγ system. Next, virtual screening integrating multiple PI3Kγ protein structures was demonstrated to significantly improve the screening enrichment rate comparing to that with an individual protein structure. Last, a multi-conformational Naïve Bayesian Classification model with the optimal docking programs was constructed, and it performed a true capability in the screening of PI3Kγ inhibitors. Taken together, the current study could provide some guidance for the docking-based virtual screening to discover novel PI3Kγ inhibitors.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34081588

RESUMO

Based on extensive applications of the time-variant quadratic programming with equality and inequality constraints (TVQPEI) problem and the effectiveness of the zeroing neural network (ZNN) to address time-variant problems, this article proposes a novel finite-time ZNN (FT-ZNN) model with a combined activation function, aimed at providing a superior efficient neurodynamic method to solve the TVQPEI problem. The remarkable properties of the FT-ZNN model are faster finite-time convergence and preferable robustness, which are analyzed in detail, where in the case of the robustness discussion, two kinds of noises (i.e., bounded constant noise and bounded time-variant noise) are taken into account. Moreover, the proposed several theorems all compute the convergent time of the nondisturbed FT-ZNN model and the disturbed FT-ZNN model approaching to the upper bound of residual error. Besides, to enhance the performance of the FT-ZNN model, a fuzzy finite-time ZNN (FFT-ZNN), which possesses a fuzzy parameter, is further presented for solving the TVQPEI problem. A simulative example about the FT-ZNN and FFT-ZNN models solving the TVQPEI problem is given, and the experimental results expectably conform to the theoretical analysis. In addition, the designed FT-ZNN model is effectually applied to the repetitive motion of the three-link redundant robot and image fusion to show its potential practical value.

19.
Pharmacol Res ; 170: 105728, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119622

RESUMO

Metabolic reprogramming, characterized by alterations of cellular metabolic patterns, is fundamentally important in supporting the malignant behaviors of cancer cells. It is considered as a promising therapeutic target against cancer. Traditional Chinese medicine (TCM) and its bioactive components have been used in cancer therapy for an extended period, and they are well-known for their multi-target pharmacological functions and fewer side effects. However, the detailed and advanced mechanisms underlying the anticancer activities of TCM remain obscure. In this review, we summarized the critical processes of cancer cell metabolic reprogramming, including glycolysis, mitochondrial oxidative phosphorylation, glutaminolysis, and fatty acid biosynthesis. Moreover, we systemically reviewed the regulatory effects of TCM and its bioactive ingredients on metabolic enzymes and/or signal pathways that may impede cancer progress. A total of 46 kinds of TCMs was reported to exert antitumor effects and/or act as chemosensitizers via regulating metabolic processes of cancer cells, and multiple targets and signaling pathways were revealed to contribute to the metabolic-modulating functions of TCM. In conclusion, TCM has its advantages in ameliorating cancer cell metabolic reprogramming by its poly-pharmacological actions. This review may shed some new light on the explicit recognition of the mechanisms of anticancer actions of TCM, leading to the development of natural antitumor drugs based on reshaping cancer cell metabolism.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33992844

RESUMO

Alterations of non-coding RNA profiling in spermatozoa are candidate mechanisms related to changes in paternal environment and progeny. Transgenerational inheritance of sex in pseudomales of Cynoglossus semilaevis, a fish with significant sex dimorphism, is a typical example of non-Mendelian inheritance. In the present study, miRNA profiles of spermatozoa were compared between male and pseudomale of C. semilaevis. Differential miRNAs in sperm from F0 and F1 generation also provides clues for revealing the possible role of non-coding RNA mediated transgenerational inheritance. Four sexual bias miRNAs, dre-miR-26a-5p, dre-miR-27b-3p, dre-miR-125b-5p,pol-199a-5p, were identified and verified in F0 and F1 generation of C. semilaevis. All of them were highly expressed in male sperm compared with pseudomale sperm. Function of target genes indicates that target genes of these differential RNAs are highly correlated with sex differentiation, gametogenesis and maintenance of secondary sexual characteristics. In a word, identification of epigenetic markers in gametes has great prospects in predicting susceptibility and properties in offsprings, and providing an indicator of parentalgenetic property.


Assuntos
Proteínas de Peixes/genética , Linguado/genética , Regulação da Expressão Gênica , Padrões de Herança , MicroRNAs/genética , Cromossomos Sexuais/genética , Diferenciação Sexual , Animais , Gametogênese , Perfilação da Expressão Gênica
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