Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.065
Filtrar
1.
BMC Cancer ; 23(1): 110, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721112

RESUMO

BACKGROUND: Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can't meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. METHODS: Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. RESULTS: A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. CONCLUSIONS: MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.


Assuntos
Adenocarcinoma de Pulmão , Quimiocinas CXC , Neoplasias Pulmonares , Midkina , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Humanos , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Quimiocinas CXC/genética , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Midkina/genética , Biomarcadores Tumorais/genética , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/genética
2.
Nanotechnology ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724503

RESUMO

The quantum transport properties of defective two-dimensional (2D) GeP semiconductor nanodevice consisting of typical point defects, such as antisite defect, substitutional defect, and Schottky defect, have been studied by using density functional theory (DFT) combined with non-equilibrium Green's function (NEGF) calculation. The antisite defect has indistinctive influences on electron transport. However, both substitutional and Schottky defect have introduced promising defect state at the Fermi level, indicating the possibility of improvement on the carrier transport. Our quantitative quantum transport calculations of I-Vbbehavior have revealed that the electrical characters are enhanced. Moreover, the P atom vacancy could induce significant negative differential resistance (NDR) phenomenon, and the physical mechanism is unveiled by detailed analysis. The transfer characteristic properties could be prominently improved by substitutional defect and vacancy defect. Most importantly, we have proposed a computational design of GeP-based electronic device with improved electrical performance by introducing vacancy defect. Our findings could be helpful to the practical application of novel 2D GeP semiconductor nanodevice in future.

3.
Phytother Res ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724888

RESUMO

Psoralen is a major component of Fructus Psoraleae that could induce liver injury. In this study, C57BL/6J mice were administered with psoralen at doses of 80 mg/kg for 3, 7 and 14 days. Blood and liver samples were collected for serum biochemistry and histopathology examinations, respectively. Psoralen led to liver injury with significantly increased liver weight and liver coefficient and up regulated serum ALT, AST and TG but down regulated serum TC and TP. The expression of bile acid-associated transporters and enzymes was detected by western blot, and the results showed that psoralen significantly down-regulates the expressions of CYP7A1, CYP27A1, BSEP and OSTα protein while up-regulates the expressions of HMGCR and FASN, resulting in the obstacles of bile acid efflux in the liver. The contents of 24 kinds of bile acids in the liver were measured by LC-MS/MS, and the results showed that psoralen led to the accumulation of unconjugated bile acids in the liver, such as ALCA and CA, which were more severe in male mice than female mice. It was indicated that psoralen may disrupt the balance of bile acid metabolism by inhibiting the expression of the efflux transporter, which then leads to liver damage.

4.
Curr Res Food Sci ; 6: 100445, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36699115

RESUMO

Maillard reaction products (MRPs) with roasted/broth flavors were prepared and analyzed for the resulting flavor differences. The identification of volatile compounds in MRPs was carried out by GC-MS and GC × GC-ToF-MS. A total of 88 compounds were identified by GC-MS; 130 compounds were identified by GC × GC-ToF-MS, especially acids and ketones were identified. Principal component analysis (PCA) was used to visualize the volatile compounds, and the roasted/broth flavors were differentiated. The contents and types of pyrazines were more in roasted flavors; thiol sulfides and thiophenes were more in broth flavors. All in all, the differences in volatile compounds producing roasted/broth flavors were studied through the cysteine-xylose-glutamate Maillard reaction system, which provided a theoretical basis for the future use of Maillard reaction to simulate meat flavor.

5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(1): 74-80, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36708119

RESUMO

Objective: Based on the clinical data of patients with foot and ankle deformities in the QIN Sihe Orthopaedic Surgery Database, to analyze the characteristics and treatment strategies of foot and ankle deformities, and provide a basis for clinical decision-making. Methods: A total of 22 062 patients with foot and ankle deformities who received orthopedic surgery between May 25, 1978 and December 31, 2020 were searched in the QIN Sihe Orthopedic Surgery Database. The gender, age at operation, regional distribution, etiology, type of deformity, operation method, postoperative fixation method, and other information were collected. Results: Among the 22 062 patients, there were 13 046 males (59.13%) and 9 016 females (40.87%); the age at operation ranged from 1 to 77 years, with a median of 17 years, and 20 026 cases (90.77%) were aged 5 to 40 years. The patients came from 32 provinces, municipalities, and autonomous regions across the China and 5 countries including India and the United States, et al. The etiology and diseases type covered 154 kinds (of which sequelae of poliomyelitis, cerebral palsy, spina bifida and tethered spinal cord, congenital equinovarus foot, post-traumatic foot and ankle deformity, and Charcot-Marie-Tooth disease accounted for the highest proportion). The types of deformities included varus foot, equinus foot, valgus foot, talipes calcaneus, equinocavus, high arched foot, claw toe, and flail foot. Surgical methods included tendon lengthening, soft tissue release, tendon transposition, osteotomy orthopedics, and ankle arthrodesis. The 36 620 operations were performed, including 11 561 cases of hip, knee, and lower leg operations to correct the foot and ankle deformities. Postoperative fixation methods included Ilizarov external fixator in 2 709 cases (12.28%), combined external fixator in 3 966 cases (17.98%), and plaster or brace fixation in 15 387 cases (69.74%). Conclusion: Male patients with foot and ankle deformities account for a large proportion, and the population distribution is mainly adolescents, with a wide distribution of regions, causes and diseases, and talipes equinovarus and varus foot are the main types of deformities. Foot and ankle deformities are often combined with deformities of other parts of the lower limb, which requires a holistic treatment concept. The application of foot soft tissue and bone surgery combined with Ilizarov external fixator and combined external fixators provides a guarantee for the correction of complex foot and ankle deformities.


Assuntos
Pé Torto Equinovaro , Técnica de Ilizarov , Ortopedia , Feminino , Adolescente , Humanos , Masculino , Tornozelo/cirurgia , Extremidade Inferior/cirurgia , Artrodese/métodos , Pé Torto Equinovaro/epidemiologia , Pé Torto Equinovaro/etiologia , Pé Torto Equinovaro/cirurgia , Resultado do Tratamento
6.
Comput Med Imaging Graph ; 104: 102176, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36682215

RESUMO

Classification of subtype and grade is imperative in the clinical diagnosis and prognosis of cancer. Many deep learning-based studies related to cancer classification are based on pathology and genomics. However, most of them are late fusion-based and require full supervision in pathology image analysis. To address these problems, we present an integrated framework for cancer classification with pathology and genomics data. This framework consists of two major parts, a weakly supervised model for extracting patch features from whole slide images (WSIs), and a hierarchical multimodal fusion model. The weakly supervised model can make full use of WSI labels, and mitigate the effects of label noises by the self-training strategy. The generic multimodal fusion model is capable of capturing deep interaction information through multi-level attention mechanisms and controlling the expressiveness of each modal representation. We validate our approach on glioma and lung cancer datasets from The Cancer Genome Atlas (TCGA). The results demonstrate that the proposed method achieves superior performance compared to state-of-the-art methods, with the competitive AUC of 0.872 and 0.977 on these two datasets respectively. This paper establishes insight on how to build deep networks on multimodal biomedical data and proposes a more general framework for pathology image analysis without pixel-level annotation.

7.
PLoS One ; 18(1): e0279190, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36634084

RESUMO

INTRODUCTION: The importance of global competence has been acknowledged in medical care as well as medical education. This study aims to develop a scale assessing the global competence of medical students, determine the factor structure and internal consistency of the scale and explore the underlying factors influencing the global competence of Chinese medical students in 8-year programs. METHODS: A questionnaire (Global Competence Assessment Scale for Medical Students, MS-GCAS) was developed, and a cross-sectional multicenter survey was conducted in 1062 medical students from 10 medical schools in China. Questionnaire data were analyzed using exploratory factor analysis and multiple linear regression. RESULTS: The exploratory factor analysis revealed a three-factor scale. The MS-GCAS has good internal consistency (Cronbach's alpha = 0.79 to 0.87). In the multivariate regression analyses, medical education stage (p<0.05), the frequency of communicating with foreigners (p<0.001), multilingual ability (p<0.05) and grade level (p<0.05) are associated with the MS-GCAS scores. DISCUSSION: The MS-GCAS has the potential to serve as a tool to measure the global competence of medical students. This three-factor scale can be used by medical education researches to improve future versions. Medical schools should conduct further educational reforms to promote students' global competence.


Assuntos
Educação Médica , Estudantes de Medicina , Humanos , Estudos Transversais , China , Inquéritos e Questionários , Competência Clínica , Reprodutibilidade dos Testes , Psicometria
8.
J Cereb Blood Flow Metab ; : 271678X231153730, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36718002

RESUMO

Synapse loss has been considered as a major pathological change in Alzheimer's disease (AD). It remains unclear about whether and how synapse loss relates to functional and structural connectivity dysfunction in AD. We measured synaptic vesicle glycoprotein 2 A (SV2A) binding using 18F-SynVesT-1 PET to evaluate synaptic alterations in 33 participants with AD, 31 with mild cognitive impairment (MCI), and 30 controls. We examined the correlation between synaptic density and cognitive function. Functional MRI was performed to analyze functional connectivity in lower synaptic density regions. We tracked the white matter tracts between impaired functional connectivity regions using Diffusion MRI. In AD group, lower synaptic density in bilateral cortex and hippocampus was found when compared with controls. The synaptic density changes in right insular cortex and bilateral caudal middle frontal gyrus (MFG) were correlated with cognitive decline. Among them, right MFG synaptic density was positively associated with right MFG - bilateral superior frontal gyrus (SFG) functional connectivity. AD had lower probability of tract (POT) between right MFG and SFG than controls, which was significantly associated with global cognition. These findings provide evidence supporting synapse loss contributes to functional and related structural connectivity alterations underlying cognitive impairment of AD.

9.
Nat Med ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702948

RESUMO

Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.

10.
Int J Biol Macromol ; 231: 123282, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657537

RESUMO

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there are still no anti-PEDV drugs with accurate targets. G-quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA, and have attracted great attention as potential targets for antiviral strategy. In this study, we reported two putative G4-forming sequences (PQS) in S and Nsp5 genes of PEDV genome based on bioinformatic analysis, and identified that S-PQS and Nsp5-PQS were enabled to fold into G4 structure by using circular dichroism spectroscopy and fluorescence turn-on assay. Furthermore, we verified that both S-PQS and Nsp5-PQS PQS could form G4 structure in live cells by immunofluorescence microscopy. In addition, G4-specific compounds, such as TMPyP4 and PDS, could significantly inhibit transcription, translation and proliferation of PEDV in vitro. Importantly, these compounds exert antiviral activity at the post-entry step of PEDV infection cycle, by inhibiting viral genome replication and protein expression. Lastly, we demonstrated that TMPyP4 can inhibit reporter gene expression by targeting G4 structure in Nsp5. Taken together, these findings not only reinforce the presence of viral G-quadruplex sequences in PEDV genome but also provide new insights into developing novel antiviral drugs targeting PEDV RNA G-quadruplexes.

11.
J Ethnopharmacol ; 306: 116146, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36610673

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbium is the resinous secretion of Euphorbia resinifera Berg. According to the record, Euphorbium was first used by Roman doctors to treat the emperor's joint pain. In China, it is applied in folk medicine to treat damp-cold or mucous diseases, such as arthralgia and ascites, etc. This herb is used for rheumatoid arthritis and skin tumors in the folklore of northeastern Brazil. Triterpenes are mainly characteristic constituents of Euphorbium, and possibly possess anti-rheumatoid arthritis. AIM OF THE STUDY: To explore the preventive effect of Euphorbium total triterpenes (TTE) on Freund's complete adjuvant (FCA) induced arthritis in rats and its mechanism. MATERIAL AND METHODS: TTE was extracted and isolated from Euphorbium, and its components were analyzed by HPLC. The safety of TTE was evaluated by an acute toxicity test in mice. Arthritis was induced in rats by injecting 0.2 mL FCA into the right hind paw toe, except for the control group, which was given the same volume of physiological saline. Tripterygium Glycosides (TG, 7.5 mg/kg) and TTE (32, 64 and 128 mg/kg) were administered by gavage for 30 days. Body weights, paw swelling, and arthritic scores were measured during the experiment process. After 30 days, blood and joints were harvested to determine various indicators of arthritis. RESULTS: The contents of euphol and euphorbol in TTE were 47.03% and 18.77% respectively, and the maximal feasible dose of TTE in mice is 12 g/kg. The experimental results showed that arthritis indicators in rats deteriorated after FCA inducement compared with the control group. After treatment with TTE, the swelling degree and histopathological change of the hind paws in rats were significantly improved as well as arthritic score; the serum TNF-α, CRP, IL-1ß, IL-6, IL-18 and RF levels in rats were significantly reduced; The expression of PI3K, AKT, P-AKT, Bcl-2, NF-κB, NLRP3 and Pro-caspase-1 protein in joint tissue were down-regulated, and the expression of Bax protein was up-regulated. CONCLUSION: The results suggested that TTE possessed anti-arthritis effects, and its mechanism may be related to its anti-inflammatory and immunomodulatory properties, as well as regulation of PI3K/AKT/Bax and NF-κB/NLRP3 signaling pathway.

12.
Cancer Imaging ; 23(1): 1, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600283

RESUMO

PURPOSE: A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa). PATIENTS AND METHODS: Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated. RESULTS: In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P < 0.001). There are non-significant differences in the CTV and GTVn based on MRI and PET/MRI images (P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage. CONCLUSION: The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Imageamento por Ressonância Magnética , Ácido Edético
13.
Small Methods ; : e2201362, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604996

RESUMO

The state-of-the-art active hydrogen evolution reaction (HER) catalysts in acid electrolytes generally lose considerable catalytic performance in alkaline electrolytes mainly due to the additional water dissociation step. Designing composite materials is an effective strategy to accelerate alkaline water electrolysis by optimizing the electronic structure of materials. Here, different phases of Co(OH)2 -supported Ru clusters (α/ß-Co(OH)2 @Ru) are prepared for enabling a highly efficient electrocatalytic HER performance in alkaline solution. The prepared α-Co(OH)2 nanosheets facilitate the loading of uniform and high-density Ru clusters and the formed highly active RuOCo bonds at the interface. The synergistic interaction endows the hybrid catalyst with low overpotential of 33 mV at 10 mA cm-2 . Moreover, the homemade anion exchange membrane water electrolysis cell based on α-Co(OH)2 @Ru affords a cell voltage of 2 V to drive a current density of 270 mA cm-2 and performs stably during continuous operation for over 100 h. Density functional theory calculations demonstrate that active RuOCo bonds in α-Co(OH)2 @Ru optimize the energy barriers for H2 O dissociation and OH- desorption to facilitate the Volmer reaction step. This work offers a strategy for designing interfacial chemical bonds for high electrocatalytic activity.

14.
Cancer Imaging ; 23(1): 6, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647150

RESUMO

BACKGROUND: Deep-learning-based computer-aided diagnosis (DL-CAD) systems using MRI for prostate cancer (PCa) detection have demonstrated good performance. Nevertheless, DL-CAD systems are vulnerable to high heterogeneities in DWI, which can interfere with DL-CAD assessments and impair performance. This study aims to compare PCa detection of DL-CAD between zoomed-field-of-view echo-planar DWI (z-DWI) and full-field-of-view DWI (f-DWI) and find the risk factors affecting DL-CAD diagnostic efficiency. METHODS: This retrospective study enrolled 354 consecutive participants who underwent MRI including T2WI, f-DWI, and z-DWI because of clinically suspected PCa. A DL-CAD was used to compare the performance of f-DWI and z-DWI both on a patient level and lesion level. We used the area under the curve (AUC) of receiver operating characteristics analysis and alternative free-response receiver operating characteristics analysis to compare the performances of DL-CAD using f- DWI and z-DWI. The risk factors affecting the DL-CAD were analyzed using logistic regression analyses. P values less than 0.05 were considered statistically significant. RESULTS: DL-CAD with z-DWI had a significantly better overall accuracy than that with f-DWI both on patient level and lesion level (AUCpatient: 0.89 vs. 0.86; AUClesion: 0.86 vs. 0.76; P < .001). The contrast-to-noise ratio (CNR) of lesions in DWI was an independent risk factor of false positives (odds ratio [OR] = 1.12; P < .001). Rectal susceptibility artifacts, lesion diameter, and apparent diffusion coefficients (ADC) were independent risk factors of both false positives (ORrectal susceptibility artifact = 5.46; ORdiameter, = 1.12; ORADC = 0.998; all P < .001) and false negatives (ORrectal susceptibility artifact = 3.31; ORdiameter = 0.82; ORADC = 1.007; all P ≤ .03) of DL-CAD. CONCLUSIONS: Z-DWI has potential to improve the detection performance of a prostate MRI based DL-CAD. TRIAL REGISTRATION: ChiCTR, NO. ChiCTR2100041834 . Registered 7 January 2021.


Assuntos
Aprendizado Profundo , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos
15.
Mol Oncol ; 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587393

RESUMO

Preclinical studies have proven that nanosecond pulsed electric field (nsPEF) ablation can be a safe and effective treatment for humans with unresectable liver cancer that are ineligible for thermal ablation. The concomitant activation of antitumor immunity by nsPEF can also potentially prevent tumor recurrence. However, whether nsPEF exhibits similar efficacy in a clinical setting remains to be investigated. A prospective clinical trial (clinicaltrials.gov identifier: NCT04039747) was conducted to evaluate the safety and efficacy of ultrasound (US)-guided nsPEF ablation in 15 patients with unresectable liver cancer that were ineligible for thermal ablation. We found that nsPEF ablation was safe and produced a 12-month recurrence-free survival (RFS) and local RFS of 60% (9/15) and 86.7% (13/15), respectively, in the enrolled patients. Integrative proteomic and metabolomic analysis showed that sphingolipid metabolism was the most significantly enriched pathway in patient sera after nsPEF without recurrence within 8 months. A similar upregulation of sphingolipid metabolism was observed in the intratumoral mononuclear phagocytes (MNPs), rather than other immune and nonimmune cells, of an nsPEF-treated mouse model. We then demonstrated that lymphocyte antigen 6 complex, locus C2-positive (Ly6c2+ ) monocytes first differentiated into Ly6c2+ monocyte-derived macrophages with an increase in sphingolipid metabolic activity, and subsequently into Ly6c2+ dendritic cells (DCs). Ly6c2+ DCs communicated with CD8+ T cells and increased the proportions of IFN-γ+ CD8+ memory T cells after nsPEF, and this finding was subsequently confirmed by depletion of liver Ly6c2+ MNPs. In conclusion, nsPEF was a safe and effective treatment for liver cancer. The alteration of sphingolipid metabolism induced by nsPEF was associated with the differentiation of Ly6c2+ MNPs, and subsequently induced the formation of memory CD8+ T cells with potent antitumor effect.

16.
Plants (Basel) ; 12(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36679082

RESUMO

Subtilisin-like proteases (subtilases) are found in almost all plant species and are involved in regulating various biotic and abiotic stresses. Although the literature on subtilases in different plant species is vast, the gene function of the serine peptidase S8 family and its maize subfamily is still unknown. Here, a bioinformatics analysis of this gene family was conducted by describing gene structure, conserved motifs, phylogenetic relationships, chromosomal distributions, gene duplications, and promoter cis-elements. In total, we identified 18 ZmSPS8 genes in maize, distributed on 7 chromosomes, and half of them were hydrophilic. Most of these proteins were located at the cell wall and had similar secondary and tertiary structures. Prediction of cis-regulatory elements in promoters illustrated that they were mainly associated with hormones and abiotic stress. Maize inbred lines B73, Zheng58, and Qi319 were used to analyze the spatial-temporal expression patterns of ZmSPS8 genes under drought treatment. Seedling drought results showed that Qi319 had the highest percent survival after 14 d of withholding irrigation, while B73 was the lowest. Leaf relative water content (LRWC) declined more rapidly in B73 and to lower values, and the nitrotetrazolium blue chloride (NBT) contents of leaves were higher in Qi319 than in the other inbreds. The qPCR results indicated that 6 serine peptidase S8 family genes were positively or negatively correlated with plant tolerance to drought stress. Our study provides a detailed analysis of the ZmSPS8s in the maize genome and finds a link between drought tolerance and the family gene expression, which was established by using different maize inbred lines.

17.
Virol J ; 20(1): 10, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650505

RESUMO

BACKGROUND: To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR. METHODS: Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency. RESULTS: Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity. CONCLUSIONS: In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.


Assuntos
Arabidopsis , Potyvirus , Interferência de RNA , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Potyvirus/genética , Tabaco , Doenças das Plantas
18.
Diabet Med ; : e15051, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692102

RESUMO

BACKGROUND: Diabetic foot ulcer (DFU) has a significantly impact on the quality of life of diabetic mellitus (DM) patients. Here, we aimed to explore the molecules with aberrant expression and their regulatory mechanisms in DFU. METHODS: The expression of genes and proteins expression was examined using qPCR and western blot. Pearson's correlation analysis was used to analyze interactions among FOXM1, GAS5 and SDF4. Immunofluorescence was used to detect PDI and GRP78 expression. Flow cytometry was used to assess cell apoptosis. Tube formation assay was used to determine angiogenic capacity. Fluorescence in situ hybridization (FISH) assay was employed to determine the cellular localization of GAS5 and SDF4 in human umbilical vein endothelial cells (HUVECs). The interactions among FOXM1, GAS5 and SDF4 were validated by chromatin immunoprecipitation (ChIP), luciferase, RNA pull-down, and RNA immunoprecipitation (RIP) assays. RESULTS: FOXM1, GAS5 and SDF4 were decreased in the skin tissues of DFU patients. High glucose (HG) stimulation induced endoplasmic reticulum (ER) stress and cell apoptosis but suppressed angiogenesis in HUVECs, which were abolished by FOXM1 overexpression. FOXM1 promoted GAS5 transcriptional activity, resulting in increased GAS5 expression, and GAS5 knockdown reversed the effects of FOXM1 overexpression in HG-treated HUVECs. Moreover, GAS5 recruited TAF15 to promote SDF4 expression in HUVECs. GAS5 overexpression inhibited ER stress, cell apoptosis, and induced angiogenesis in HG-treated HUVECs which could be reversed by silencing SDF4. CONCLUSION: Our results revealed that FOXM1 suppressed ER stress, cell apoptosis, and promoted angiogenesis in HG-induced HUVECs via mediating GAS5/TAF15/SDF4 axis, providing a novel therapeutic molecule mechanism for DFU.

19.
Res Sq ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36712010

RESUMO

Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFb activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFb kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.

20.
Cell Mol Immunol ; 20(2): 143-157, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36596875

RESUMO

Due to their broad functional plasticity, myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury (APAP-ALI). A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment. Here, we identified the function of IFN-I in the myeloid compartment during APAP-ALI. Utilizing single-cell RNA sequencing, we characterized the cellular atlas and dynamic progression of liver CD11b+ cells post APAP-ALI in WT and STAT2 T403A mice, which was further validated by immunofluorescence staining, bulk RNA-seq, and functional experiments in vitro and in vivo. We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages, leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+ restorative macrophage maturation, contributing to efficient liver repair. Overall, we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Animais , Camundongos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Neutrófilos/metabolismo , Macrófagos , Camundongos Endogâmicos C57BL , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...