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1.
Strahlenther Onkol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649484

RESUMO

BACKGROUND: Alopecia causes significant distress for patients and negatively impacts quality of life for low-grade glioma (LGG) patients. We aimed to compare and evaluate variations in dose distribution for scalp-sparing in LGG patients with proton therapy and photon therapy, namely intensity-modulated proton therapy (IMPT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT). METHODS: This retrospective study utilized a dataset comprising imaging data from 22 patients with LGG who underwent postoperative radiotherapy. Treatment plans were generated for each patient with scalp-optimized (SO) approaches and scalp-non-optimized (SNO) approaches using proton techniques and photons techniques; all plans adhered to the same dose constraint of delivering a total radiation dose of 54.04 Gy to the target volume. All treatment plans were subsequently analyzed. RESULTS: All the plans generated in this study met the dose constraints for the target volume and OARs. The SO plans resulted in reduced maximum scalp dose (Dmax), mean scalp dose (Dmean), and volume of the scalp receiving 30 Gy (V30) and 40 Gy (V40) compared with SNO plans in all radiation techniques. Among all radiation techniques, the IMPT plans exhibited superior performance compared to other plans for dose homogeneity as for SO plans. Also, IMPT showed lower values for Dmean and Dmax than all photon radiation techniques. CONCLUSION: Our study provides evidence that the SO approach is a feasible technique for reducing scalp radiation dose. However, it is imperative to conduct prospective trials to assess the benefits associated with this approach.

2.
Plant Physiol ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488068

RESUMO

Potato (Solanum tuberosum L.) is cultivated worldwide for its underground tubers, which provide an important part of human nutrition and serve as a model system for below-ground storage organ formation. Similar to flowering, stolon-expressed FLOWERING LOCUS T-like (FT-like) protein SELF-PRUNING 6A (StSP6A) plays an instrumental role in tuberization by binding to the bZIP transcription factors StABI5-like 1 (StABL1) and StFD-like 1 (StFDL1), causing transcriptional reprogramming at the stolon subapical apices. However, the molecular mechanism regulating the widely conserved FT-bZIP interactions remains largely unexplored. Here, we identified a TCP transcription factor StAST1 (StABL1 and StSP6A-associated TCP protein 1) binding to both StSP6A and StABL1. StAST1 is specifically expressed in the vascular tissue of leaves and developing stolons. Silencing of StAST1 leads to accelerated tuberization and a shortened life cycle. Molecular dissection reveals that the interaction of StAST1 with StSP6A and StABL1 attenuates the formation of the alternative tuberigen activation complex (aTAC). We also observed StAST1 directly activates the expression of potato GA 20-oxidase gene (StGA20ox1) to regulate GA responses. These results demonstrate StAST1 functions as a tuberization repressor by regulating plant hormone levels; our findings also suggest a mechanism by which the widely conserved FT-FD genetic module is fine-tuned.

3.
Int J Biol Sci ; 20(5): 1871-1883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481804

RESUMO

Radiotherapy (RT) stands as the primary treatment for tumors, but it inevitably causes damage to normal cells. Consequently, radiation injury is a crucial consideration for radiation oncologists during therapy planning. Cell death including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis play significant roles in tumor treatment. While previous studies elucidated the induction of apoptosis and autophagy by ionizing radiation (IR), recent attention has shifted to pyroptosis, ferroptosis, and necroptosis, revealing their effects induced by IR. This review aims to summarize the strategies employed by IR, either alone or in combination therapy, to induce pyroptosis, ferroptosis, and necroptosis in radiation injury. Furthermore, we explore their effects and molecular pathways, shedding light on their roles in radiation injury. Finally, we summarize the regulative agents for these three types of cell death and their mechanisms. In summary, optimizing radiation dose, dose rate, and combined treatment plans to minimize radiation damage and enhance the killing effect of RT is a key focus.


Assuntos
Ferroptose , Lesões por Radiação , Humanos , Piroptose , Necroptose , Apoptose
4.
Front Pharmacol ; 15: 1333128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375030

RESUMO

Background: Tumor treating fields (TTF) was first approved for treatment of glioblastoma. Recently, the LUNAR study demonstrated that TTF + standard therapy (ST) extended survival in patients with advanced non-small cell lung cancer (NSCLC). This primary objective of this study is to analyze the cost-effectiveness of this treatment from the United States healthcare payers' perspective. Methods: A 3-health-state Markov model was established to compare the cost-effectiveness of TTF + ST and that of ST alone. Clinical data were extracted from the LUNAR study, supplemented by additional cost and utility data obtained from publications or online sources. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted. The willingness-to-pay (WTP) threshold per quality-adjusted life-years (QALYs) gained was set to $150,000. The main results include total costs, QALYs, incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB). Subgroup analyses were conducted for two types of ST, including immune checkpoint inhibitor, and docetaxel. Results: During a 10-year time horizon, the costs of TTF + ST and ST alone were $431,207.0 and $128,125.9, and the QALYs were 1.809 and 1.124, respectively. The ICER of TTF + ST compared to ST was $442,732.7 per QALY, and the INMB was -$200,395.7 at the WTP threshold. The cost of TTF per month was the most influential factor in cost-effectiveness, and TTF + ST had a 0% probability of being cost-effective at the WTP threshold compared with ST alone. Conclusion: TTF + ST is not a cost-effective treatment for advanced NSCLC patients who progressed after platinum-based therapy from the perspective of the United States healthcare payers.

6.
J Ethnopharmacol ; 311: 116466, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37031821

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of renal fibrosis caused by chronic kidney disease is increasing year by year. Preventing the activation and conversion of kidney-intrinsic fibroblasts to a myofibroblast phenotype is an important target for blocking the development of renal interstitial fibrosis. Our team established a stable renal interstitial fibrosis cell model in the early stage, and the screening results showed that GPs has good anti-fibrosis potential. At this stage, only a few literatures have reported its anti-fibrosis effect, and the mechanism of action is still unclear. AIM OF THE STUDY: The massive synthesis and secretion of extracellular-matrix (ECM) components by activated fibroblasts in the kidneys causes irreversible renal interstitial fibrosis. Gypenosides (GPs) have been shown to decelerate this process, in which micro RNAs (miRNAs) play an important regulatory role. This study aimed to evaluate the mechanism underlying the suppressive effect of GPs on renal fibrosis. MATERIALS AND METHODS: This study used TGF-ß1-stimulated NRK-49F renal cells as an in-vitro model of renal interstitial fibrosis. First, the concentration range of GPs that significantly affects the cytoactive was determined. Then, the anti-fibrotic effects of various concentrations of GPs in the in-vitro model were assessed via immunofluorescence, western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Non-coding-RNA sequencing combined with bioinformatics was used to predict the mechanistic basis of the anti-fibrotic effect of GPs, and qRT-PCR was used to verify the sequencing results and bioinformatic predictions. The identified relationships of the anti-fibrotic effect of GPs with miR-378a-5p and the PI3K/AKT signaling were evaluated using a miR-NC mimic and the PI3K inhibitor LY294002 as controls, respectively. RESULTS: TGF-ß1 stimulation up-regulated α-SMA, COL1, and COL3 in NRK-49F cells, and this effect was suppressed by GPs. Additionally, TGF-ß1 stimulation significantly changed the expression levels of 151 miRNAs, and GPs significantly suppressed the effect of TGF-ß1 on the levels of 18 of these miRNAs. Among them, miR-3588 and miR-378a-5p were down-regulated, and miR-135b-5p and miR-3068-5p were up-regulated upon TGF-ß1 induction. Of these miRNAs, miR-378a-5p was predicted to target the mRNAs of numerous proteins mainly enriched in the PI3K/AKT signaling pathway. The miRNA transfection experiments with the miR-NC mimic and PI3K inhibitor as controls showed that miR-378a-5p overexpression could suppress the TGF-ß1-induced up-regulation of α-SMA, COL1, PI3K, and AKT, including the phosphorylated form (p-AKT). CONCLUSION: GPs inhibit the PI3K/AKT signaling by up-regulating miR-378a-5p in TGF-ß1-stimulated NRK-49F cells and thereby reduce their massive secretion of ECM components. Given that this in-vitro model of renal interstitial fibrosis closely mimics the in-vivo pathogenesis, our results most likely apply to the in-vivo conditions.


Assuntos
Nefropatias , MicroRNAs , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Rim , Transdução de Sinais , Nefropatias/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose
7.
Mil Med Res ; 10(1): 13, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36907884

RESUMO

BACKGROUND: Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis. We hypothesized that pericytes, a group of pluripotent cells that maintain vascular integrity and tension, are protective against sepsis via regulating vascular reactivity and permeability. METHODS: We conducted a series of in vivo experiments using wild-type (WT), platelet-derived growth factor receptor beta (PDGFR-ß)-Cre + mT/mG transgenic mice and Tie2-Cre + Cx43flox/flox mice to examine the relative contribution of pericytes in sepsis, either induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. In a separate set of experiments with Sprague-Dawley (SD) rats, pericytes were depleted using CP-673451, a selective PDGFR-ß inhibitor, at a dosage of 40 mg/(kg·d) for 7 consecutive days. Cultured pericytes, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were used for mechanistic investigations. The effects of pericytes and pericyte-derived microvesicles (PCMVs) and candidate miRNAs on vascular reactivity and barrier function were also examined. RESULTS: CLP and LPS induced severe injury/loss of pericytes, vascular hyporeactivity and leakage (P < 0.05). Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization (P < 0.05). Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels (P < 0.05). Additionally, PCMVs transferred miR-145 and miR-132 to VSMCs and VECs, respectively, exerting a protective effect on vascular reactivity and barrier function after sepsis (P < 0.05). miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2 (Sphk2)/sphingosine-1-phosphate receptor (S1PR)1/phosphorylation of myosin light chain 20 pathway, whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways. CONCLUSIONS: Pericytes are protective against sepsis through regulating vascular reactivity and barrier function. Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.


Assuntos
MicroRNAs , Sepse , Animais , Camundongos , Ratos , Permeabilidade Capilar/fisiologia , Conexina 43/metabolismo , Células Endoteliais/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/farmacologia , Pericitos/metabolismo , Ratos Sprague-Dawley
8.
Angew Chem Int Ed Engl ; 61(48): e202208937, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36197752

RESUMO

Halide perovskite has been widely studied as a new generation of photoelectronic materials. However, their thermal and humidity-induced emission quenching have greatly limited their utility and reliability. Here, we report a hexagonal Mn2+ -doped CsCdCl3 perovskite crystal that possesses stable photoluminescence (PL) at both high temperature and humidity. The room temperature long-persistent luminescence (LPL) of the single crystals lasts up to 1480 s and can be adjusted by changing the concentration of Mn2+ ion doping. The characteristic emission of d-d transition of Mn2+ is realized, and the photoluminescence quantum yield (PLQY) is up to 91.4 %, it can maintain more than 90 % of the initial PL spectral integral area at 150 °C (423 K). High humid stability PL can be achieved more than 75 % of the initial PL intensity after 55 days of immersion in water. These excellent properties show the application prospect of the LPL material in lighting indication and anti-counterfeiting.

9.
Front Physiol ; 13: 948541, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262250

RESUMO

Vascular hyperpermeability is a complication of hemorrhagic shock. Pericytes (PCs) are a group of mural cells surrounded by microvessels that are located on the basolateral side of the endothelium. Previous studies have shown that damage to PCs contributes to the occurrence of many diseases such as diabetic retinopathy and myocardial infarction. Whether PCs can protect the vascular barrier function following hemorrhagic shock and the underlying mechanisms are unknown. A hemorrhagic shock rat model, Cx43 vascular endothelial cell (VEC)-specific knockdown mice, and VECs were used to investigate the role of PCs in vascular barrier function and their relationship with Cx43. The results showed that following hemorrhagic shock, the number of PCs in the microvessels was significantly decreased and was negatively associated with an increase in pulmonary and mesenteric vascular permeability. Exogenous infusion of PCs (106 cells per rat) colonized the microvessels and improved pulmonary and mesenteric vascular barrier function. Upregulation of Cx43 in PCs significantly increased the number of PCs colonizing the pulmonary vessels. In contrast, downregulation of Cx43 expression in PCs or knockout of Cx43 in VECs (Cx43 KO mice) significantly reduced PC colonization in pulmonary vessels in vivo and reduced direct contact formation between PCs and VECs in vitro. It has been suggested that PCs have an important protective effect on vascular barrier function in pulmonary and peripheral vessels following hemorrhagic shock. Cx43 plays an important role in the colonization of exogenous PCs in the microvessels. This finding provides a potential new shock treatment measure.

10.
J Oncol ; 2022: 7733251, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124031

RESUMO

Background: Sex, age, and International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic risk may influence the immune response. Nonetheless, the correlation between these factors and the survival benefits of immune-based combination therapies in patients with metastatic renal cell carcinoma (mRCC) is controversial and undefined. As a result, the purpose of this research is to evaluate the potential differences of immune-based combination therapies on survival benefits from mRCC subgroups. Methods: PubMed, Cochrane Library, Embase, and http://www.clinicaltrials.gov were searched from inception to March 17, 2022. Randomized clinical trials (RCTs) comparing overall survival (OS) or progression-free survival (PFS) in patients with mRCC treated by immune-based combinations vs. contemporary first-line therapies were included. Results: Five RCTs with a total of 4206 subjects were included. An OS and PFS benefit of immune-based combinations were found for patients of different sex, age, and IMDC intermediate/poor risk. No obvious difference in relative PFS benefit from immune-based combinations over the control group was found in patients of different genders (P=0.71, I2 = 0%), ages (P=0.55, I2 = 0%), or IMDC prognostic risks (P=0.38, I2 = 0%). However, the difference in OS benefit was significant regarding age (P=0.009, I2 = 85.5%) and IMDC prognostic risk (P=0.004, I2 = 82.2%). Conclusions: This meta-analysis found that immune-based combination therapies should not be restricted to certain patients with mRCC in gender categories. However, age and IMDC prognostic risk of mRCC patients are associated with different outcomes of OS and thus help identify those patients most probably to benefit from immune-based combination therapies.

11.
Phys Chem Chem Phys ; 24(17): 9866-9874, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35363243

RESUMO

As we know, defects caused in the synthetic process of metal halide perovskite are the most difficult to overcome, and greatly limit their photoelectric performances. Herein, a post-doped strategy was utilized to achieve an interesting morphology evolution from a standard octahedron to a snowflake-like sheet during the Mn2+-doped Cs2NaBiCl6 process, which realizes the obvious photoluminescence quantum efficiency (PLQY) enhancement of the Cs2NaBiCl6:Mn2+ phosphor. This surprising evolution is ascribed to the morphology collapse and reconstruction induced by Mn2+ exchange. The obtained phosphor exhibits enhanced 31.56% PLQY, which is two-fold higher than that synthesized by the traditional co-precipitation method, with broad emission spectrum and good PL color stability at 150 °C. Combined with the Cs2SnCl6 : 1mol%Bi3+ phosphor to fabricate the phosphor-converted light-emitting diode, bright white light emission with Ra = 88, CCT = 4320 K, CIE (0.36, 0.33) and a good application potential in high-resolution PL imaging agents was obtained. This work provides a possible effective strategy to improve the PL performance for impurity-doped lead-free metal halide perovskite.

12.
Front Pharmacol ; 13: 1021584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703730

RESUMO

Background: Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD). Method: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195). Results: A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 post hoc analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06-1.26, p = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30-0.64, p < .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups. Conclusion: In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.

13.
Transl Cancer Res ; 11(12): 4409-4415, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36644177

RESUMO

Background: Tongue squamous cell carcinoma (TSCC) is the most common subtype of oral cavity squamous cell carcinoma (OCSCC), and it also has the worst prognosis. It is crucial to find an effective way to solve the challenges in diagnosis and prognosis prediction for TSCC. Machine learning (ML) has been widely used in medical research and has shown good performance. It can be used for feature extraction, feature selection, model construction, etc. Radiomics and deep learning (DL), the new components of ML, have also been utilized to explore the relationship between image features and diseases. The current study aimed to highlight the importance of ML as a potential method for addressing the challenges in diagnosis and prognosis prediction of TSCC by reviewing studies on ML in TSCC. Methods: The studies on ML in TSCC in PubMed, Scopus, Web of Science, and China National Knowledge Infrastructure published between the dates of inception of these databases and April 30, 2022, were reviewed. Key Content and Findings: ML (including radiomics and DL) which was used in diagnosis and prognosis prediction for TSCC, has shown promising performance. Conclusions: Despite its limitations, ML is still a potential approach that can help to deal with the challenges in diagnosis and prognosis prediction for TSCC. Nevertheless, more efforts are needed to enhance the usefulness of ML in this field.

14.
Transl Androl Urol ; 11(12): 1729-1734, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36632167

RESUMO

Background: Radical prostatectomy is the standard of care in patients with prostate cancer. Robot-assisted prostatectomy have been used as alternatives to open surgery as they result in less bleeding and allow patients to return to normal activities sooner. This study sought to evaluate the medical factors and health economics of robot-assisted and laparoscopic-assisted prostate cancer surgery to provide a valuable reference for clinicians, patients, and their families when selecting a surgical method for prostate cancer. Methods: Patients treated with Da Vinci robot-assisted surgery (DVRS) or laparoscopic-assisted surgery (LS) between January 1, 2019, and June 1, 2021, were included in this retrospective analysis. The general baseline data included age, height, weight, body mass index (BMI), preoperative total prostate specific antigen (TPSA), Gleason score, tumor stage, operation time, intraoperative blood loss volume, hospital stay, drainage volume within 24 hours postoperatively, extubation time, postoperative hospital stay, and detailed hospitalization expenditure. The medical and health economics factors were compared between the two prostatectomy techniques. Results: The preoperative characteristics of the patients in the DVRS group and LS group were comparable, and the differences were not statistically significant (all P>0.05). Compared to the LS group, the operation time was significantly longer in the DVRS group, whereas the volume of intraoperative blood loss, hospital stay, extubation time, and postoperative hospital stay were all markedly lower (all P<0.05). Also, the treatment, nursing, and total operation costs were considerably lower in the DVRS group compared to the LS group, while the medical material cost, total hospitalization cost, and personal expenses were all notably higher (all P<0.05). Conclusions: Da Vinci robot-assisted prostatectomy is safe; however, the health economics should not be neglected that the robot-assisted operation cannot completely replace the conventional laparoscopic operation in the short term. The consideration of both clinical efficacy and health economics is necessary to provide suggestions for the choice of modus operandi.

15.
Inorg Chem ; 60(20): 15519-15528, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34617745

RESUMO

Cyan-emitting phosphors are important for near-ultraviolet (NUV) light-emitting diodes (LEDs) to gain high-quality white lighting. In the present work, a Bi3+-doped BaScO2F, R+ (R = Na, K, Rb) perovskite, which emits 506 nm cyan-green light under 360 or 415 nm excitation, is obtained via a high-temperature solid-state method for the first time. The obtained perovskite shows improved photoluminescence and thermal stability due to the charge compensation of Na+, K+, and Rb+ co-doping. Its spectral broadening is attributed to two centers Bi (1) and Bi (2), which are caused by the zone-boundary octahedral tilting due to the substitution of Bi3+ for the larger Ba2+. Employing the blend phosphors of Ba0.998ScO2F:0.001Bi3+,0.001K+ and the commercial BAM:Eu2+, YAG:Ce3+, and CaAlSiN3:Eu2+, a full-spectrum white LED device with Ra = 96 and CCT = 4434 K was fabricated with a 360 nm NUV chip. Interestingly, a novel strategy is proposed: the cyan-green Ba0.998ScO2F:0.001Bi3+,0.001K+ and orange Sr3SiO5:Eu2+ phosphors were packaged with a 415 nm NUV chip to produce the white LED with Ra = 85 and CCT = 4811 K.

16.
Brief Bioinform ; 22(6)2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34368838

RESUMO

The advent of large-scale biomedical data and computational algorithms provides new opportunities for drug repurposing and discovery. It is of great interest to find an appropriate data representation and modeling method to facilitate these studies. The anatomical therapeutic chemical (ATC) classification system, proposed by the World Health Organization (WHO), is an essential source of information for drug repurposing and discovery. Besides, computational methods are applied to predict drug ATC classification. We conducted a systematic review of ATC computational prediction studies and revealed the differences in data sets, data representation, algorithm approaches, and evaluation metrics. We then proposed a deep fusion learning (DFL) framework to optimize the ATC prediction model, namely DeepATC. The methods based on graph convolutional network, inferring biological network and multimodel attentive fusion network were applied in DeepATC to extract the molecular topological information and low-dimensional representation from the molecular graph and heterogeneous biological networks. The results indicated that DeepATC achieved superior model performance with area under the curve (AUC) value at 0.968. Furthermore, the DFL framework was performed for the transcriptome data-based ATC prediction, as well as another independent task that is significantly relevant to drug discovery, namely drug-target interaction. The DFL-based model achieved excellent performance in the above-extended validation task, suggesting that the idea of aggregating the heterogeneous biological network and node's (molecule or protein) self-topological features will bring inspiration for broader drug repurposing and discovery research.


Assuntos
Aprendizado Profundo , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos , Algoritmos , Bases de Dados de Compostos Químicos , Modelos Químicos , Proteínas/metabolismo
17.
Front Pharmacol ; 11: 1262, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973506

RESUMO

This study was designed to investigate the mechanism by which MMDD improves lung function, and observe the effect of MMDD on endoplasmic reticulum stress(ERS) in alveolar type II epithelial cells (AECIIs) of pulmonary fibrosis rats. pulmonary fibrosis animal model was established by intratracheal injection of BLM at a dose of 6mg/kg body weight. Overall, Thirty male SPF Sprague-Dawley rats were randomly divided into control group, BLM group and BLM+MMDD group. BLM+MMDD group rats were fed 24 g/kg over three weeks for twice a day on the fourteenth day after model establishment. MMDD improves pulmonary function of fibrotic rats and reduces the occurrence of endoplasmic reticulum stress in AECIIs. MMDD could significantly improve the forced vital capacity (FVC) of bleomycin-induced pulmonary fibrosis in rats. MMDD reduced the expression of GRP78 and CHOP in AECIIs, increased the secretion of surfactant protein C (SPC) by AECIIs. Moreover, the apoptosis of the fibrosis zone in the lung tissue was remarkably mitigated by administration of MMDD. The finding of this study revealed that MMDD can improve lung function in rats with pulmonary fibrosis by reducing the occurrence of ERS and cell apoptosis of AECIIs. It may provide a new method for the treatment of pulmonary fibrosis.

18.
Chin J Traumatol ; 23(2): 89-95, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32192909

RESUMO

Pericyte, a kind of pluripotent cell, may regulate the irrigation flow and permeability of microcirculation. Pericytes are similar to the smooth muscle cells, which express several kinds of contractile proteins and have contractility. The dysfunction of pericytes is related to many microvascular diseases, including hypoxia, hypertension, diabetic retinopathy, fibrosis, inflammation, Alzheimer's disease, multiple sclerosis, and tumor formation. For a long time, their existence and function have been neglected. The distribution, structure, biomarker, related signaling pathways as well as the roles of pericytes on vascular diseases will be introduced in this review.


Assuntos
Pericitos , Pesquisa , Proteínas Contráteis/metabolismo , Humanos , Microcirculação , Pericitos/química , Pericitos/patologia , Pericitos/fisiologia , Doenças Vasculares/etiologia
19.
BMJ Open ; 9(2): e026920, 2019 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-30804037

RESUMO

INTRODUCTION: Pre-eclampsia is an important cause of death and complication for pregnant women and perinatal infant. Low-dose aspirin has been most commonly used to prevent pre-eclampsia in high-risk pregnant women. Recently, heparins have also been used alone or in combination with aspirin to prevent pre-eclampsia. However, the optimal doses and combination therapy of aspirin and heparins are not well established. Therefore, we aim to compare aspirin, heparins and their combination to prevent pre-eclampsia in a network meta-analysis. METHODS AND ANALYSIS: We will search the following electronic databases from the date of database establishment to 8 January 2019: PubMed, Embase, Cochrane Library, Web of Science and ProQuest. We will also search additional studies manually. There will be no restriction on the language of publications. Only randomised clinical trials will be eligible in our network meta-analysis. We will include pregnant women who have been recommended for aspirin according to the standard of the American Congress of Obstetricians and Gynecologists, or were designated as high risk in some recent studies. We will include studies comparing the effects of any single or combination of aspirin and heparins with placebo or observation or another intervention in pregnancy. We will include studies that reported one of the following outcomes: pre-eclampsia, severe pre-eclampsia, preterm delivery, perinatal death and full-term pre-eclampsia with delivery at ≥37 weeks. Traditional pairwise meta-analysis will be performed initially, and then network meta-analysis will be performed using frequency analysis method. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. ETHICS AND DISSEMINATION: This network meta-analysis does not require ethical certification. An overview and information on the prevention of pre-eclampsia in high-risk pregnant women will be provided by this network meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42018084248.


Assuntos
Aspirina/administração & dosagem , Heparina/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Complicações na Gravidez/prevenção & controle , Feminino , Humanos , Recém-Nascido , Metanálise em Rede , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
20.
Chem Commun (Camb) ; 54(22): 2751-2754, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29479604

RESUMO

We designed and synthesized three phosphorylated peptides as precursors of the same peptide Nap-YYY. We found that different precursors led to different materials with almost identical chemical compositions at the final stages. Only Nap-YpYY could form very uniform nanofibers in a stable supramolecular hydrogel by enzyme-instructed self-assembly (EISA) at the physiological temperature (37 °C). In contrast, de-phosphorylation of the other two precursors (Nap-pYYY and Nap-YYpY) resulted in diverse nanostructures in metastable hydrogels with precipitates. The formation of uniform nanomaterials in the stable hydrogels was due to the preorganization property of the precursor Nap-YpYY, which facilitated rapid folding and accelerated the kinetics of hydrogelation of the resulting peptide Nap-YYY generated by the EISA process. Our study demonstrated the importance of the precursor for the self-assembly of nanomaterials and provided a useful strategy to manipulate them.

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