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1.
Acta Pharmacol Sin ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658427

RESUMO

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.

2.
Strahlenther Onkol ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688953

RESUMO

OBJECTIVE: This study aimed to improve the image quality and CT Hounsfield unit accuracy of daily cone-beam computed tomography (CBCT) using registration generative adversarial networks (RegGAN) and apply synthetic CT (sCT) images to dose calculations in radiotherapy. METHODS: The CBCT/planning CT images of 150 esophageal cancer patients undergoing radiotherapy were used for training (120 patients) and testing (30 patients). An unsupervised deep-learning method, the 2.5D RegGAN model with an adaptively trained registration network, was proposed, through which sCT images were generated. The quality of deep-learning-generated sCT images was quantitatively compared to the reference deformed CT (dCT) image using mean absolute error (MAE), root mean square error (RMSE) of Hounsfield units (HU), and peak signal-to-noise ratio (PSNR). The dose calculation accuracy was further evaluated for esophageal cancer radiotherapy plans, and the same plans were calculated on dCT, CBCT, and sCT images. RESULTS: The quality of sCT images produced by RegGAN was significantly improved compared to the original CBCT images. ReGAN achieved image quality in the testing patients with MAE sCT vs. CBCT: 43.7 ± 4.8 vs. 80.1 ± 9.1; RMSE sCT vs. CBCT: 67.2 ± 12.4 vs. 124.2 ± 21.8; and PSNR sCT vs. CBCT: 27.9 ± 5.6 vs. 21.3 ± 4.2. The sCT images generated by the RegGAN model showed superior accuracy on dose calculation, with higher gamma passing rates (93.3 ± 4.4, 90.4 ± 5.2, and 84.3 ± 6.6) compared to original CBCT images (89.6 ± 5.7, 85.7 ± 6.9, and 72.5 ± 12.5) under the criteria of 3 mm/3%, 2 mm/2%, and 1 mm/1%, respectively. CONCLUSION: The proposed deep-learning RegGAN model seems promising for generation of high-quality sCT images from stand-alone thoracic CBCT images in an efficient way and thus has the potential to support CBCT-based esophageal cancer adaptive radiotherapy.

3.
Toxicology ; 484: 153389, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36481571

RESUMO

To investigate the potential factors of graphene quantum dots (GQDs), the assessment impact on the innate immune system is one of the most important. As the innate immune cell, macrophages possess phagocytosis activity and affect immunomodulation. Higher oxygen consumption rates (OCR) are used to gain insight into GQDs' effects on macrophages. Metabolomics profiling also revealed that GQDs exposure provoked an increase in phosphoglycerides, sphingolipids, and oxidized lipids in macrophages. The molecular pathways disrupted by GQDs were associated with lipid and energy metabolisms. Metabolite flux analysis was used to evaluate changes in the lipid metabolism of macrophages exposed to 100 µg mL-1 GQDs for 24 and 48 h. A combination of 13C-flux analysis and metabolomics revealed the regulation of lipid biosynthesis influenced the balance of energy metabolism. Integrated proteomics and metabolomics analyses showed that nicotinic acid adenine dinucleotide and coenzyme Q10 were significantly increased under GQDs treatment, alongside upregulated protein activity (e.g., Cox5b and Cd36). The experimental evidences were expected to be provided in this study to reveal the potential harmful effect from exposure to GQDs.


Assuntos
Grafite , Pontos Quânticos , Grafite/toxicidade , Pontos Quânticos/toxicidade , Metabolismo dos Lipídeos , Macrófagos/metabolismo , Homeostase
4.
Inorg Chem ; 62(1): 520-529, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36563080

RESUMO

Metal nanoclusters (NCs) have been unleashed as an emerging category of metal materials by virtue of integrated merits including the unusual atom-stacking mode, quantum confinement effect, and fruitful catalytically active sites. Nonetheless, development of metal NCs as photosensitizers is blocked by light-induced instability and ultrashort carrier lifespan, which remarkably retards the design of metal NC-involved photosystems, hence resulting in the decreased photoactivities. To solve these obstacles, herein, we conceptually probed the charge transfer characteristics of the BiVO4 photoanode photosensitized by atomically precise alloy metal NCs, wherein tailor-made l-glutathione-capped gold-silver bimetallic (AuAg) NCs were controllably self-assembled on the BiVO4 substrate. It was uncovered that alien Ag atom doping is able to effectively stabilize the alloy AuAg NCs and simultaneously photosensitize the BiVO4 photoanode, significantly boosting the photoelectrochemical (PEC) water oxidation performances. The reasons for the robust and stable PEC water oxidation activities of the AuAg NCs/BiVO4 composite photoanode were unambiguously unleashed. We ascertain that Ag atom doping in the staple motif of Aux NCs efficaciously protects the NCs from rapid oxidation, enhancing the photostability, boosting the photosensitization efficiency, and thus leading to the considerably improved PEC water splitting activities compared with the homometallic counterpart. This work could afford a new strategy to judiciously tackle the inherent detrimental instability of metal NCs for solar energy conversion.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36459386

RESUMO

Bacterial vaginosis (BV) is a common vaginal disease associated with abnormal changes in the vaginal microbiome. Our previous study found that Lactobacillus rhamnosus has a good therapeutic effect on bacterial vaginosis by inhibiting the most prominent bacterium associated with BV, Gardnerella vaginalis. In this study, we show that acetic acid and lactic acid are the main substances in the cell-free supernatant (CFS) of L. rhamnosus that inhibit the growth of G. vaginalis. Further study on the mechanism showed that acetic acid and lactic acid alter the morphology of the G. vaginalis cells, eventually causing the cells to shrink or burst, resulting in exudation of their intracellular contents. In addition, these two organic acids also dissipate the membrane potential of bacterial cells, affecting their synthesis of ATP. A reduced activity of the Na+/K+-ATPase leads to abnormal ATP metabolism, and ultimately inhibits the growth and reproduction of G. vaginalis. Our study provides valuable information for the widespread application of L. rhamnosus in the treatment of bacterial vaginosis.

6.
Sleep ; 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36462192

RESUMO

STUDY OBJECTIVES: To investigate the relationship between sleep transition dynamics and stage-specific functional connectivity (FC) of the anterior cingulate cortex (ACC) in patients with insomnia disorder (ID). METHODS: Simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data from thirty-seven patients with ID and thirty well-matched healthy controls (HCs) were recorded during wakefulness and different sleep stages and subsequently analyzed. A Markov chain model was used to estimate the transition probability between each stage. The FC between the ACC (set as the seed) and voxels across the whole brain was calculated. A linear mixed effect model was used to determine the group-by-stage interaction of the seed-based connectivity. The correlation between the sleep-stage transition probability and the ACC-based connectivity was explored. RESULTS: Patients with ID exhibited a higher likelihood of transitioning from N2 to wakefulness than HCs. A significant group-by-stage interaction of connectivity with the bilateral ACC was observed in the cerebellar, subcortical and cortical regions. Moreover, a significant positive correlation was found in patients with ID between the transition probability from N2 to wakefulness and the FC of the ACC with the anterior cerebellum in N2 (r = 0.48). CONCLUSIONS: This exploratory analysis indicates that enhanced FC between the ACC and cerebellum represents a potential neural pathway underlying the greater likelihood of patients with ID waking during N2 sleep. These findings contribute to an emerging framework that reveals the link between sleep maintenance difficulty and ACC function, further highlighting the possibility that N2 sleep is a therapeutic target for meaningfully reducing sleep disruption.

7.
Nat Commun ; 13(1): 7417, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456554

RESUMO

Opportunistic bacterial pathogen species and their strains that colonise the human gut are generally understood to compete against both each other and the commensal species colonising this ecosystem. Currently we are lacking a population-wide quantification of strain-level colonisation dynamics and the relationship of colonisation potential to prevalence in disease, and how ecological factors might be modulating these. Here, using a combination of latest high-resolution metagenomics and strain-level genomic epidemiology methods we performed a characterisation of the competition and colonisation dynamics for a longitudinal cohort of neonatal gut microbiomes. We found strong inter- and intra-species competition dynamics in the gut colonisation process, but also a number of synergistic relationships among several species belonging to genus Klebsiella, which includes the prominent human pathogen Klebsiella pneumoniae. No evidence of preferential colonisation by hospital-adapted pathogen lineages in either vaginal or caesarean section birth groups was detected. Our analysis further enabled unbiased assessment of strain-level colonisation potential of extra-intestinal pathogenic Escherichia coli (ExPEC) in comparison with their propensity to cause bloodstream infections. Our study highlights the importance of systematic surveillance of bacterial gut pathogens, not only from disease but also from carriage state, to better inform therapies and preventive medicine in the future.


Assuntos
Cesárea , Ecossistema , Feminino , Gravidez , Recém-Nascido , Humanos , Klebsiella , Metagenômica , Parto , Escherichia coli/genética
8.
Front Endocrinol (Lausanne) ; 13: 1029066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531502

RESUMO

Purpose: This study aimed to assess the clinical usefulness of widefield swept source optical coherence tomography angiography (WF SS-OCTA) for detecting microvasculature lesions in diabetic retinopathy (DR) by comparing it with ultra-widefield fluorescein angiography (UWFFA) and to investigate the effect of panretinal photocoagulation (PRP) on posterior vitreous detachment (PVD) status. Methods: Patients with severe non-proliferative DR (NPDR) or proliferative DR (PDR) who were initially treated with PRP were enrolled. They underwent WF SS-OCTA with a 12×12-mm scan pattern of five visual fixations at baseline and at least a 3-month follow-up after PRP treatment. Patients with no contraindications underwent imaging with UWFFA within a week. Images were evaluated using two methods for the areas of the visible field of view (FOV), non-perfusion area (NPA), presence of neovascularization of the disc (NVD), neovascularization elsewhere (NVE), and PVD status. Results: In total, 44 eyes of 28 patients with DR that were initially treated with PRP were analyzed. The FOV of the UWFFA was significantly wider than that of the WF SS-OCTA. The quantitative measurement of the NPAs was consistent between the two methods. NPAs more than 5DA outside the panoramic OCTA imaging area were detected in 1 eye with NPDR (8.3%) and in 10 eyes with PDR (47.8%). WF SS-OCTA had high detection rates for NVDs and NVEs, with a low rate of false positives. After PRP treatment, no eyes indicated progression in the PVD stages around the macula, optical disc, or NVEs at the short follow-up. Conclusion: WF SS-OCTA is clinically useful for evaluating NPAs and neovascularization in DR. PRP treatment does not induce PVD development in the short term.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Neovascularização Retiniana , Descolamento do Vítreo , Humanos , Retinopatia Diabética/diagnóstico , Tomografia de Coerência Óptica/métodos , Vasos Retinianos/patologia , Neovascularização Retiniana/diagnóstico , Neovascularização Retiniana/cirurgia , Descolamento do Vítreo/patologia , Descolamento do Vítreo/cirurgia , Angiofluoresceinografia/métodos , Retina/diagnóstico por imagem , Retina/cirurgia , Neovascularização Patológica/patologia , Fotocoagulação
9.
Am J Transl Res ; 14(10): 7164-7171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398263

RESUMO

OBJECTIVE: To investigate the prevalence of myopia among children and adolescents in a local area (Liyang City) of China and analyze the influencing factors, so as to formulate corresponding preventive measures. METHODS: A questionnaire survey was conducted, mainly investigating subjects' age, gender, residence (urban/rural areas), parental myopia, daily time spent outdoors, daily sleep time, distance between computer screen and eyes, less than one punch (10 cm) from the chest to the edge of the desk when reading and writing, one inch (3 cm) between finger and pen tip when writing, number of in-school physical education (PE) classes, length of TV watching, and size of TV. The myopia of all participants was recorded. RESULTS: This study enrolled 7,948 children and adolescents, including 4,733 (59.55%) cases of myopia, 1,025 (12.90%) of astigmatism, 251 (3.16%) of hyperopia, and 699 (8.79%) of anisometropia respectively. There were 2,519 (53.22%) cases of myopia in the left eye and 2,214 (46.78%) in the right eye. Low, moderate, and high myopia were determined in 2,682 (56.67%), 1,583 (33.45%), and 468 (9.89%), respectively. In terms of spherical equivalent (SEQ), a statistically lower SEQ was observed in urban areas (-1.56±0.46 d) versus suburban counties (-1.17±0.33 d), and in females (-1.68±0.30 d) compared with males (-1.17±0.44 d). The mean SEQ gradually decreased with age. The prevalence of myopia was 63.84% (2,436/3,816) in females, statistically higher than that of 55.59% (2,197/4,132) in males (χ2=56.00, P < 0.0001). The incidence of myopia was statistically higher in urban areas (67.93% [3,321/4,889]) versus rural areas (46.16% [1,412/3,059]). Parental myopia, one inch between finger and pen tip when writing, daily time spent outdoors, daily sleep time, distance between computer screen and eyes, less than one punch from the chest to the edge of the desk when reading and writing, number of in-school PE classes, and daily length of TV watching were significantly correlated with the occurrence of myopia. CONCLUSIONS: Parents are advised to pay attention to daily time spent outdoors, sleep time, distance between the computer screen and the eyes, distance between the chest and the edge of the table when reading and writing, and length of TV watching of their children. As far as schools are concerned, PE activity time should be properly maintained to ensure that children have enough outdoor exercise time to reduce eye fatigue.

10.
Gates Open Res ; 6: 77, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36415883

RESUMO

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.

11.
Radiat Oncol ; 17(1): 188, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397060

RESUMO

BACKGROUND: This study was designed to establish radiation pneumonitis (RP) prediction models using dosiomics and/or deep learning-based radiomics (DLR) features based on 3D dose distribution. METHODS: A total of 140 patients with non-small cell lung cancer who received stereotactic body radiation therapy (SBRT) were retrospectively included in this study. These patients were randomly divided into the training (n = 112) and test (n = 28) sets. Besides, 107 dosiomics features were extracted by Pyradiomics, and 1316 DLR features were extracted by ResNet50. Feature visualization was performed based on Spearman's correlation coefficients, and feature selection was performed based on the least absolute shrinkage and selection operator. Three different models were constructed based on random forest, including (1) a dosiomics model (a model constructed based on dosiomics features), (2) a DLR model (a model constructed based on DLR features), and (3) a hybrid model (a model constructed based on dosiomics and DLR features). Subsequently, the performance of these three models was compared with receiver operating characteristic curves. Finally, these dosiomics and DLR features were analyzed with Spearman's correlation coefficients. RESULTS: In the training set, the area under the curve (AUC) of the dosiomics, DLR, and hybrid models was 0.9986, 0.9992, and 0.9993, respectively; the accuracy of these three models was 0.9643, 0.9464, and 0.9642, respectively. In the test set, the AUC of these three models was 0.8462, 0.8750, and 0.9000, respectively; the accuracy of these three models was 0.8214, 0.7857, and 0.8571, respectively. The hybrid model based on dosiomics and DLR features outperformed other two models. Correlation analysis between dosiomics features and DLR features showed weak correlations. The dosiomics features that correlated DLR features with the Spearman's rho |ρ| ≥ 0.8 were all first-order features. CONCLUSION: The hybrid features based on dosiomics and DLR features from 3D dose distribution could improve the performance of RP prediction after SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Pneumonite por Radiação , Radiocirurgia , Humanos , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia
12.
Front Surg ; 9: 984892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338638

RESUMO

Background: The goal of the current study was to explore the application of preoperative three-dimensional reconstruction (3DR) based on thin-slice magnetic resonance imaging (MRI) in the simultaneous guidance of en bloc tumor resection and adjacent perforator flap elevation. Methods: The prospective cohort included 35 patients diagnosed with either soft tissue sarcoma or squamous cell skin cancer between 2019 and 2021. The preoperative 3DR based on thin-slice MRI illustrated the spatial anatomical relationship among the tumor, underlying muscle, adjacent perforator vessels, and bone around the surgical region. The accuracy of preoperative imaging data was verified by intraoperative vessel dissection and postoperative pathological measurements. Results: Tumor size from 3DR data showed relatively high concordance rates with pathological measurements within the 95% limits of agreement. An average of three perforators (range: 1-7) with a mean diameter of 0.32 cm (range: 0.18-0.74 cm) from the 3DR were present in our study. The average distance between tumor boundary and perforator piercing sites on the 3DR was 2.2 cm (range: 1.2-7.7 cm). The average length of artery perforator coursing along the subcutaneous tissue was 5.8 cm (range: 3.3-25.1 cm). The mean flap harvest time was 55 mins (range: 36-97 min). The average flap size was 92.2 cm2 (range: 32-126 cm2). One perforator flap occurred distal partial necrosis. Conclusion: A thorough understanding of anatomical structures in the surgical region according to full-field 3DR based on thin-slice MRI can improve the performance of radical resection of the tumor and adjacent perforator flap transfer, especially for junior surgeons with a poor experience.

13.
Emerg Med Int ; 2022: 1284254, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212997

RESUMO

Background: Intracranial atherosclerotic stenosis (ICAS) causes a series of neurological symptoms, such as vertigo, impaired consciousness, limb weakness, ataxia, dysphagia, ocular motility disorders, and visual impairment. With the improvement of people's living standards, there are higher requirements for nursing care. Nursing, as an indispensable part of medical care, is closely related to achieving the goal of patient's safety and the overall quality of nurses, quality of care, and nursing management methods. Objective: To explore the effect of risk-centered diversified safety management in patients undergoing aortic stenting. Methods: Eighty patients with cerebral infarction were selected and treated with percutaneous transluminal angioplasty and stent implantation (PTAS). Then they were divided into a control group (40 cases) with routine monitoring and an experimental group (40 cases) with risk-focused intervention of a diversified safety management model according to the mode of care. Patient satisfaction and blood index test results were compared after the intervention. Results: Patients in the experimental group had 6 falls, 3 bed falls, 3 phlebitis, 4 tube slips, and 10 deep vein thrombosis, all significantly fewer than those in the control group. Thirty-eight patients in the experimental group expressed satisfaction with safe management, which was substantially better than the control group (P < 0.05). The levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PA1-1), and von Willebrand factor (vWF) in the experimental group were (13.5 ± 1.3) ng/mL, (60.1 ± 9.9) ng/mL, and (2.1 ± 0.2), respectively, which were substantially lower than those in the control group ((14.6 ± 2.4) ng/mL, (64.2 ± 10.7) ng/mL, and (2.8 ± 0.3)), respectively (P < 0.05). Conclusion: The risk-centered diversified safety management model can effectively reduce the probability of adverse events in patients, improve patient satisfaction with nursing services, and promote faster postoperative recovery, which has clinical application value.

14.
Nanoscale Res Lett ; 17(1): 102, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36301360

RESUMO

Light-stimulated synaptic devices are promising candidates for the development of artificial intelligence systems because of their unique properties, which include broad bandwidths, low power consumption, and superior parallelism. The key to develop such devices is the realization of photoelectric synaptic behavior in them. In this work, visible-light-stimulated synaptic transistors based on CdSe quantum dot (CdSe QD)/amorphous In-Ga-Zn-O hybrid channels are proposed. This design can not only improve the charge separation efficiency of the photogenerated carriers, but also can induce delayed decay of the photocurrent. The improved charge separation efficiency enhances the photoelectric properties significantly, while the delayed decay of the photocurrent led to the realization of photoelectric synaptic behaviors. This simple and efficient method of fabricating light-stimulated phototransistors may inspire new research progress into the development of artificial intelligence systems.

15.
Front Genet ; 13: 984714, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186420

RESUMO

Background: G-protein signaling modulator 2 (GPSM2) maintains cell polarization and regulates the cell cycle. Recent studies have shown that it is highly expressed in various tumors, but its pan-cancer analysis has not been reported. Methods: First, we analyzed the differential GPSM2 expression in normal and cancer tissues by the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas databases and investigated its expression effect on the survival of cancer patients by gene expression profiling interactive analysis 2 (GEPIA2). Second, we analyzed the GPSM2 phosphorylation level using the clinical proteomic tumor analysis consortium dataset. In addition, we investigated GPSM2 gene mutations in human tumor specimens and the impact of gene mutations on patient survival. Finally, we analyzed the relationship between GPSM2 expression and cellular immune infiltration through the TIMER 2.0 database. Meanwhile, the possible signaling pathway of the gene was analyzed by the Gene Ontology (GO)| Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to explore its potential mechanism. Results: GPSM2 is overexpressed in most cancers, which leads to reduced overall survival (OS) and disease-free survival in patients. The results of phosphorylation analysis suggest that tumor development involves a complex GPSM2 phosphorylation process. We identified GPSM2 mutation loci with the highest frequency of mutations in uterine corpus endometrial carcinoma (UCEC), and this mutation increased progression-free survival and overall survival in uterine corpus endometrial carcinoma patients. Finally, we found that the role of GPSM2 in tumors may be associated with cellular immune infiltration. Gene Ontology|KEGG pathway analysis showed that the enrichment pathways were mainly "mitotic nuclear division," "chromosome segregation," and "spindle." Conclusions: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles and potential mechanisms of GPSM2 in multiple human cancers.

16.
Eur J Ophthalmol ; : 11206721221127159, 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36120856

RESUMO

INTRODUCTION: To report a successful application of dexamethasone implants in the treatment of a massive amount of persistent subretinal fluid (SRF) following a tractional retinal detachment (TRD) surgery. CASE REPORT: A 44-year-old woman was found to have SRF 1 week after a diabetic TRD surgery. The central macular thickness (CMT) reached up to 1.47 mm and remained high after a month's observation. For better restoration, 2 dexamethasone implants (Ozurdex) were applied at postoperative week 5 and 32 respectively and got good outcomes. The SRF decrease showed a close correlation with Ozurdex treatments: The CMT declined quickly in the next 16 weeks both after 2 times of Ozurdex applications (the linear regression slopes of CMT changes: -12.54 and -22.94, respectively). In contrast, in the interval of 2 injections, the CMT had few changes (the slope: -4.667) even if applying an anti-VEGF agent. Eventually, SRF was completely resolved 48 weeks after the surgery. DISCUSSION: Dexamethasone implant can be an option for effective treatment of persistent SRF after TRD repair, especially in some refractory cases. However, the mechanism remains unclear, and the treatment regimen needs to be explored based on more clinical trials.

17.
Front Chem ; 10: 971540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059874

RESUMO

This work investigated the removal of cadmium ions (Cd2+) by using biochar derived from Barracuda Grass. The biochars derived from the pyrolysis of roots (BGR), stems (BGS) and leaves (BGL) were characterized and their performance for cadmium adsorption was studied at varying parameters of temperature, time, and alkali (earth) metal concentrations. The maximum adsorption amount at equilibrium of BGR, BGS and BGL was determined experimentally as 8.38 mg/g, 42.12 mg/g, and 30.39 mg/g. Adsorption fitting results revealed that Cd2+ adsorbed on BGR and BGS preferred to be multilayer-covered, and BGL was more likely to have monolayer-covered functions. The kinetic data fitted well to the pseudo-second-order model (R 2 > 0.99), revealing the adsorption process was a spontaneous monolayer chemisorption process. The results of alkaline (earth) metals leaching of biochar revealed that the inherent alkaline (earth) metals in biochar made inhibitory functions on the Cd2+ adsorption behavior by occupying the active sites. And in the process of wastewater treatment, the leaching of alkaline earth metals might enhance the complexation reaction between surface groups and Cd2+. This study provides a feasible strategy for the resource utilization of abundant hydrophytic plants in waste management.

18.
Aesthetic Plast Surg ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123508

RESUMO

OBJECTIVE: Topical injection of growth factor (GF) for facial rejuvenation is unauthorized, but it is commonly performed in China, leading to emerging and challenging complications. The purpose of this study is to investigate the clinical, imaging, and histopathologic characteristics of complications caused by facial GF injection, as well as their treatments and outcomes. METHODS: We performed a retrospective single-centered case series study on consecutive patients who were treated for complications following facial injection of GF. The primary outcome was the recurrence over follow-up period. The secondary outcomes were the subjective evaluations of the facial aesthetic, symptomatic, and psychological improvements using the Global Aesthetic Improvement Scale (GAIS) and a patient-reported outcome measurement (PROM). Kaplan-Meier analysis and log-rank test were performed to investigate the recurrence. RESULTS: A total of 32 females with an average age of 42.6 ± 9.4 years were included. Most patients received GF injections in non-medical institutes such as beauty spas and presented with uncontrollable soft tissue hyperplasia, diffuse subcutaneous swelling, and skin redness. Ultrasonography showed heterogeneous hypoechoic or echogenic areas in a thickened and disorganized subcutaneous tissue hierarchy. MRI showed flaky isointensive or hypointensive signals on T1WI and hyperintensive signals on T2WI. 37.5% patient underwent triamcinolone acetonide injection, whereas 62.5% patients underwent surgical interventions. Lipoma-like hyperplastic tissue was found during surgery. HE staining confirmed intramuscular lipoma and fibrolipomatous tissue hyperplasia. Recurrence was found in 37.5% patients over a median follow-up of 6 months. KM curves and log-rank test demonstrated no significant difference in the recurrence between patients who underwent nonsurgical or surgical interventions (p = 0.77). GAIS and PROM scores indicated substantial aesthetic, symptomatic, and psychological improvements in 70%, 91.7%, and 75% patients, respectively. CONCLUSIONS: Both surgical and nonsurgical interventions are feasible and effective treatment options for GF-induced complications. Although recurrence rate was relatively high, aesthetic, symptomatic, and psychological improvements were achieved in most patients. We developed a workflow that might help diagnose and treat complications following unknown dermal filler injections. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

19.
Drug Des Devel Ther ; 16: 3241-3262, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172053

RESUMO

Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.


Assuntos
Retinopatia Diabética , Edema Macular , Fatores de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Ranibizumab , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
20.
Bioorg Chem ; 128: 106066, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35964500

RESUMO

Podophyllotoxin's undifferentiated cytotoxicity and poor selectivity limit its clinical application. To improve above disadvantages, conjugation of bile acids with podophyllotoxin could improve cell line selectivity of liver cancer to achieve clinical translation further. Enlightened by the bile acids' moiety magic characters, thirty podophyllotoxin-linked bile acid derivatives had been designed and synthesized. The cytotoxicity of these compounds in vitro was evaluated on HepG2, HCT-116, A549 and MDCK cell lines. After conjunction with bile acids, most of the derivatives (IC50 = 0.066-0.831 µM) were more potent against above three types of tumor cells than Etoposide (VP-16, IC50 = 4.319-41.080 µM) and exhibited similar antitumor activity compared with doxorubicin (DOX, IC50 = 0.230-0.745 µM). Moreover, structure-activity relationship displayed the length of the linker chain between podophyllotoxin and bile acids affected the cytotoxicity. Especially, compound 23 exhibited strong activity against HepG2 cell lines (IC50 = 0.188 ± 0.01 µM) than MDCK cell lines (IC50 = 4.780 ± 0.50 µM) and its SI (IC50MDCK/IC50HepG2) value of compound 23 was 25.4. Further antitumor mechanism studies showed that compound 23 acted as Topo Ⅱ inhibition and induced cell apoptosis with S cell cycle arrest. In particular, compound 23 showed valid antitumor efficacy at 10 mg/kg by intraperitoneal administration with a tumor inhibition rate of 60.9% in the Hepa1-6 xenograft mice model. The current research displayed that introduction of bile acids contributed to improve selectivity and activity to cell, and compound 23 could be a promising anti-tumor candidate.


Assuntos
Antineoplásicos , Neoplasias , Animais , Antineoplásicos/farmacologia , Apoptose , Ácidos e Sais Biliares/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Etoposídeo/farmacologia , Glucosídeos/farmacologia , Humanos , Camundongos , Estrutura Molecular , Podofilotoxina , Relação Estrutura-Atividade
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