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1.
Artigo em Inglês | MEDLINE | ID: mdl-39095065

RESUMO

OBJECTIVE: The purpose of this study is to explore the impact of deep learning image reconstruction (DLIR) algorithm on the quantification of radiomic features in ultra-low-dose computed tomography (ULD-CT) compared with adaptive statistical iterative reconstruction-Veo (ASIR-V). METHODS: One hundred eighty-three patients with pulmonary nodules underwent standard-dose computed tomography (SDCT) (4.30 ± 0.36 mSv) and ULD-CT (UL-A, 0.57 ± 0.09 mSv or UL-B, 0.33 ± 0.04 mSv). SDCT was the reference standard using (ASIR-V) at 50% strength (50%ASIR-V). ULD-CT was reconstructed with 50%ASIR-V, DLIR at medium and high strength (DLIR-M, DLIR-H). Radiomics analysis extracted 102 features, and the intraclass correlation coefficient (ICC) quantified reproducibility between ULD-CT and SDCT reconstructed by 50%ASIR-V, DLIR-M, and DLIR-H for each feature. RESULTS: Among 102 radiomic features, the percentages of reproducibility of 50%ASIR-V, DLIR-M, and DLIR-H were 48.04% (49/102), 49.02% (50/102), and 52.94% (54/102), respectively. Shape and first order features demonstrated high reproducibility across different reconstruction algorithms and radiation doses, with mean ICC values exceeding 0.75. In texture features, DLIR-M and DLIR-H showed improved mean ICC values for pure ground glass nodules (pGGNs) from 0.69 ± 0.23 to 0.75 ± 0.18 and 0.81 ± 0.12, respectively, compared with 50%ASIR-V. Similarly, the mean ICC values for solid nodules (SNs) increased from 0.60 ± 0.19 to 0.66 ± 0.14 and 0.69 ± 0.13, respectively. Additionally, the mean ICC values of texture features for pGGNs and SNs in both ULD-CT groups decreased with reduced radiation dose. CONCLUSIONS: DLIR can improve the reproducibility of radiomic features at ultra-low doses compared with ASIR-V. In addition, pGGNs showed better reproducibility at ultra-low doses than SNs.

2.
J Appl Clin Med Phys ; 25(8): e14412, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38807292

RESUMO

PURPOSE: To investigate the enhancement of image quality achieved through the utilization of SnapShot Freeze 2 (SSF2), a comparison was made against the results obtained from the original SnapShot Freeze algorithm (SSF) and standard motion correction (STND) in stent patients undergoing coronary CT angiography (CCTA) across the entire range of heart rates. MATERIALS AND METHODS: A total of 118 patients who underwent CCTA, were retrospectively included in this study. Images of these patients were reconstructed using three different algorithms: SSF2, SSF, and STND. Objective assessments include signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diameters of stents and artifact index (AI). The image quality was subjectively evaluated by two readers. RESULTS: Compared with SSF and STND, SSF2 had similar or even higher quality in the parameters (AI, SNR, CNR, inner diameters) of coronary artery, stent, myocardium, MV (mitral valve), TV (tricuspid valve), AV (aorta valve), and PV (pulmonary valve), and aortic root (AO). Besides the above structures, SSF2 also demonstrated comparable or even higher subjective scores in atrial septum (AS), ventricular septum (VS), and pulmonary artery root (PA). Furthermore, the enhancement in image quality with SSF2 was significantly greater in the high heart rate group compared to the low heart rate group. Moreover, the improvement in both high and low heart rate groups was better in the SSF2 group compared to the SSF and STND group. Besides, when using the three algorithms, an effect of heart rate variability on stent image quality was not detected. CONCLUSION: Compared to SSF and STND, SSF2 can enhance the image quality of whole-heart structures and mitigate artifacts of coronary stents. Furthermore, SSF2 has demonstrated a significant improvement in the image quality for patients with a heart rate equal to or higher than 85 bpm.


Assuntos
Algoritmos , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Frequência Cardíaca , Processamento de Imagem Assistida por Computador , Razão Sinal-Ruído , Stents , Humanos , Angiografia por Tomografia Computadorizada/métodos , Estudos Retrospectivos , Angiografia Coronária/métodos , Frequência Cardíaca/fisiologia , Feminino , Masculino , Pessoa de Meia-Idade , Processamento de Imagem Assistida por Computador/métodos , Idoso , Artefatos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Vasos Coronários/diagnóstico por imagem
3.
Bioorg Med Chem ; 79: 117167, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36682225

RESUMO

Pseudomonas aeruginosa is widely attributed as the leading cause of hospital-acquired infections. Due to intrinsic antibiotic resistance mechanisms and the ability to form biofilms, P. aeruginosa infections are challenging to treat. P. aeruginosa employs multiple virulence mechanisms to establish infections, many of which are controlled by the global virulence regulator Vfr. An attractive strategy to combat P. aeruginosa infections is thus the use of anti-virulence compounds. Here, we report the discovery that FDA-approved drug auranofin attenuates virulence pathways in P. aeruginosa, including quorum sensing (QS) and Type IV pili (TFP). We show that auranofin acts via multiple targets, one of which being Vfr. Consistent with inhibition of QS and TFP expression, we show that auranofin attenuates biofilm maturation, and when used in combination with colistin, displays strong synergy in eradicating P. aeruginosa biofilms. Auranofin may have immediate applications as an anti-virulence drug against P. aeruginosa infections.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/metabolismo , Auranofina/farmacologia , Auranofina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fatores de Virulência/metabolismo , Fatores de Virulência/farmacologia , Fatores de Virulência/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Biofilmes , Percepção de Quorum , Proteínas de Bactérias/farmacologia
4.
J Bacteriol ; 204(7): e0061521, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35758750

RESUMO

Enterococcus faecalis is often coisolated with Pseudomonas aeruginosa in polymicrobial biofilm-associated infections of wounds and the urinary tract. As a defense strategy, the host innately restricts iron availability at infection sites. Despite their coprevalence, the polymicrobial interactions of these two species in biofilms and under iron-restricted conditions remain unexplored. Here, we show that E. faecalis inhibits P. aeruginosa growth within biofilms when iron is restricted. E. faecalis lactate dehydrogenase (ldh1) gives rise to l-lactate production during fermentative growth. We find that an E. faecalis ldh1 mutant fails to inhibit P. aeruginosa growth. Additionally, we demonstrate that ldh1 expression is induced under iron-restricted conditions, resulting in increased lactic acid exported and, consequently, a reduction in local environmental pH. Together, our results suggest that E. faecalis synergistically inhibits P. aeruginosa growth by decreasing environmental pH and l-lactate-mediated iron chelation. Overall, this study emphasizes the importance of the microenvironment in polymicrobial interactions and how manipulating the microenvironment can impact the growth trajectory of bacterial communities. IMPORTANCE Many infections are polymicrobial and biofilm-associated in nature. Iron is essential for many metabolic processes and plays an important role in controlling infections, where the host restricts iron as a defense mechanism against invading pathogens. However, polymicrobial interactions between pathogens are underexplored under iron-restricted conditions. Here, we explore the polymicrobial interactions between commonly coisolated E. faecalis and P. aeruginosa within biofilms. We find that E. faecalis modulates the microenvironment by exporting lactic acid which further chelates already limited iron and also lowers the environmental pH to antagonize P. aeruginosa growth under iron-restricted conditions. Our findings provide insights into polymicrobial interactions between bacteria and how manipulating the microenvironment can be taken advantage of to better control infections.


Assuntos
Enterococcus faecalis , Pseudomonas aeruginosa , Biofilmes , Enterococcus faecalis/metabolismo , Ferro/metabolismo , Ácido Láctico/metabolismo , Pseudomonas aeruginosa/metabolismo
5.
J Cell Biochem ; 120(7): 11241-11247, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30790324

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized progressive memory loss and cognitive impairment. In previous studies, the activities of extracts of Chinese medicinal herbs to treat brain function disorders caused by AD have already been reported. ZiShen prescription was a traditional Chinese medicine (TCM) compound prescription reformed for AD disease based on the basic theory of TCM. To explore the effect of ZiShen (kidney-reinforcing) prescription on the learning and memory abilities, we made compound AD model rats by injecting d-galactose and ibotenic acid into the abdominal cavity to damage both sides of the nucleus basalis of Meynert with ibotenic acid. The trisected Y-maze was used to test the learning and memory abilities of AD model rats before and after treatment by ZiShen prescription and Piracetam. To investigate the mechanism of ZiShen prescription, the expressions of apoptosis-related genes (Bcl-2/Bax) in the cortex and hippocampus of compound AD model rats were detected in the cortex and hippocampus. The results show that, comparing with Piracetam, a clinical medicine to promote the thinking and memory for AD patients, ZiShen prescription significantly increased the learning and memory abilities of the compound AD model rats. After the treatment of ZiShen prescription, the expression of Bcl-2 was upregulated, along with a downregulation of Bax in the cortex and hippocampus of compound AD model rats. And the results indicated that the clinical benefits of ZiShen prescription were slightly better than Piracetam. Still, further well-designed studies are required to ensure the clinical effect of ZiShen.

6.
Mediators Inflamm ; 2016: 9348037, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26980948

RESUMO

Acute lung injury (ALI) induced by intestinal ischemia/reperfusion (II/R) has high incidence and mortality, in which IL-1ß was essential for the full development of ALI. However, the detailed regulating mechanism for this phenomenon remains to be unclear. The purpose of this study was to investigate whether inhibition of P38 MAPK could downregulate the expression of IL-1ß to protect lung from acute injury in II/R rats. Here, we found that the level of pulmonary edema at 16 hours after operation (hpo) was obviously enhanced compared to that in 8hpo and sham groups. Immunofluorescent staining demonstrated that IL-1ß and P38 MAPK were detected in lung tissues. And rats with II/R have the highest translation level for IL-1ß and phosphorylation of P38 MAPK in lung tissues at 16hpo compared with 8hpo and sham groups. Moreover, administration of SB239063, an inhibitor of P38 α and ß, could effectively downregulate the expressions of IL-1ß and protects lung tissues from injury in II/R rats. Our findings indicate that the inhibition of P38 α and ß may downregulate the expression of IL-1ß to protect lung from acute injury in II/R, which could be used as a potential target for reducing ALI induced by II/R in the future clinical trial.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Interleucina-1beta/metabolismo , Pulmão/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Inibidores Enzimáticos/uso terapêutico , Pulmão/patologia , Masculino , Fosforilação , Edema Pulmonar/metabolismo , Edema Pulmonar/patologia , Edema Pulmonar/prevenção & controle , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
7.
Zhongguo Zhong Yao Za Zhi ; 39(19): 3836-40, 2014 Oct.
Artigo em Zh | MEDLINE | ID: mdl-25612450

RESUMO

Natural products especially flavonoids are being explored for their therapeutic potentials in reducing bone loss and maintaining bone health. The present study is to investigate the effects of isoquercitrin from Craibiodendron yunnanense with different concentrations at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7) mol x L(-1) on proliferation, differentiation and mineralization of MC3T3-E1. Cell proliferation was assessed by CCK-8 kit at 1, 3, 5 and 7 days of culture. Alkaline phosphatase (ALP) activity were performed qualitatively and quantitatively on day 7, and alizarin red S staining was employed to access the mineralization of cells on day 21. The osteogenic markers ALP, collagen type I (COL 1A1), runt-related transcription factor 2 (Runx-2) and Osterix were detected to analysis early osteogenic differentiation of cells on day 3 by RT-PCR. The results showed that isoquercitrin had a dose-dependent effect on the proliferation, osteogenic differentiation, mineralization and gene expression of MC3T3-E1 in the range from 1 x 10(-7) to 1 x 10(-5) mol x L(-1). At concentrations above 1 x 10(-4) mol x L(-1) isoquercitrin showed cytotoxicity, while 1 x 10(-6) mol x L(-1) is the optimal concentration of isoquercitrin to improve the osteoblastic activity. All these results implied that isoquercitrin might be the major composition of traditional Chinese medicine C. yunnanense to treat bone fractures.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Ericaceae/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Quercetina/análogos & derivados , Fosfatase Alcalina/metabolismo , Animais , Linhagem Celular , Colágeno Tipo I/metabolismo , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Quercetina/farmacologia
8.
Acad Radiol ; 31(1): 69-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37821344

RESUMO

RATIONALE AND OBJECTIVES: To explore indicators of neuropsychological changes in patients with type 1 narcolepsy (NT1) using resting-state functional magnetic resonance imaging (rs-fMRI). MATERIALS AND METHODS: Thirty-four NT1 patients and 34 age- and sex-matched healthy volunteers were recruited for neuropsychiatric assessments and rs-fMRI data acquisition. Fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and related brain functional connectivity (FC) were calculated for the two groups and compared using a two-sample t test with cluster-level FDR correction. Moreover, partial correlation analysis was performed between these functional values of changed brain regions and clinical scales. RESULTS: Compared to those of healthy controls, spontaneous functional activities were significantly weakened in patients with NT1 in regions such as the left/right posterior cerebellum lobe, left inferior temporal gyrus, and left dorsolateral superior frontal gyrus, whereas those in regions such as the left middle occipital gyrus, right inferior occipital gyrus, and left/right lingual gyrus were significantly strengthened. Furthermore, NT1 patients displayed significantly changed FCs between the left/right anterior cingulate gyrus (ACG) and regions such as the left/right cerebellum, left middle occipital gyrus, and left inferior frontal gyrus in the operculum. In partial correlation analysis, the functions in the left dorsolateral superior frontal gyrus were significantly related to the Trail Making Tests (TMT) score. Moreover, the FC between the left ACG and left inferior frontal gyrus in the operculum was highly correlated with anxiety and depression features, including the Hamilton Anxiety Scale (HAMA) score and Hamilton Depression Rating Scale (HAMD-17) score. CONCLUSION: Patients with NT1 exhibited abnormalities in the anterior cingulate cortex, frontal-parietal cortex, hippocampus, and left/right posterior cerebellum lobe. The deactivation of the left frontal-temporal cortex is stronger, which is involved in the cognitive decline and mental disorders in these patients. Damage to the ACG may affect its FC with other regions and cause cognition and emotion dysregulation, perhaps by impairing patients' visual pathways and frontal-temporal-parietal networks. Hence, these could be important biomarkers for their neuropsychological changes.


Assuntos
Imageamento por Ressonância Magnética , Narcolepsia , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Narcolepsia/diagnóstico por imagem , Lobo Occipital
9.
Brain Behav ; 14(6): e3551, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38849983

RESUMO

INTRODUCTION: Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression. METHODS: We conducted a two-sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome-wide association studies (GWASs) and the largest GWAS meta-analysis. MR analysis mainly used inverse-variance weighted method; supplementary methods included weighted median, weighted mode, and MR-Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy. RESULTS: After adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01-1.02, p = 2.96 × E - 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04-1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10-1.42, p = 6.46 × E - 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19-1.94, p ≤ 8.94 × E - 4). CONCLUSION: There is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.


Assuntos
Depressão , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoartrite , Humanos , Análise da Randomização Mendeliana/métodos , Depressão/genética , Depressão/epidemiologia , Osteoartrite/genética , Osteoartrite/epidemiologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/epidemiologia , Artrite/genética , Artrite/epidemiologia , Artrite Reumatoide/genética , Artrite Reumatoide/epidemiologia , Gota/genética , Gota/epidemiologia , Fatores de Risco , Espondilartrite/genética
10.
Front Oncol ; 14: 1301649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357206

RESUMO

Purpose: We investigated the value of magnetic resonance imaging (MRI) histogram features, a non-invasive method, in assessing the changes in chemoresistance of colorectal cancer xenografts in rats. Methods: A total of 50 tumor-bearing mice with colorectal cancer were randomly divided into two groups: control group and 5-fluorouracil (5-FU) group. The MRI histogram characteristics and the expression levels of p53 protein and MRP1 were obtained at 24 h, 48 h, 72 h, 120 h, and 168 h after treatment. Results: Sixty highly repeatable MRI histogram features were obtained. There were 16 MRI histogram parameters and MRP1 resistance protein differences between groups. At 24 h after treatment, the MRI histogram texture parameters of T2-weighted imaging (T2WI) images (10%, 90%, median, energy, and RootMeanSquared) and D images (10% and Range) were positively correlated with MRP1 (r = 0.925, p = 0.005). At 48 h after treatment, histogram texture parameters of apparent diffusion coefficient (ADC) images (Energy) were positively correlated with the presence of MRP1 resistance protein (r = 0.900, p = 0.037). There was no statistically significant difference between MRI histogram features and p53 protein expression level. Conclusions: MRI histogram texture parameters based on T2WI, D, and ADC maps can help to predict the change of 5-FU resistance in colorectal cancer in the early stage and provide important reference significance for clinical treatment.

11.
Nat Commun ; 15(1): 4283, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769318

RESUMO

The genome of Pseudomonas aeruginosa encodes three type VI secretion systems, each comprising a dozen distinct proteins, which deliver toxins upon T6SS sheath contraction. The least conserved T6SS component, TssA, has variations in size which influence domain organisation and structure. Here we show that the TssA Nt1 domain interacts directly with the sheath in a specific manner, while the C-terminus is essential for oligomerisation. We built chimeric TssA proteins by swapping C-termini and showed that these can be functional even when made of domains from different TssA sub-groups. Functional specificity requires the Nt1 domain, while the origin of the C-terminal domain is more permissive for T6SS function. We identify two regions in short TssA proteins, loop and hairpin, that contribute to sheath binding. We propose a docking mechanism of TssA proteins with the sheath, and a model for how sheath assembly is coordinated by TssA proteins from this position.


Assuntos
Proteínas de Bactérias , Domínios Proteicos , Pseudomonas aeruginosa , Sistemas de Secreção Tipo VI , Sistemas de Secreção Tipo VI/metabolismo , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/química , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Ligação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética
12.
mBio ; 15(1): e0238423, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38078746

RESUMO

IMPORTANCE: Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for E. faecalis acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by E. faecalis during acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment in E. faecalis wound pathogenesis and how these metabolic pathways can be targeted to better control wound infections.


Assuntos
Infecções Urinárias , Infecção dos Ferimentos , Animais , Camundongos , Enterococcus faecalis/genética , Enterococcus faecalis/metabolismo , Carboidratos , Purinas
13.
J Neurosci Res ; 91(6): 786-98, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23553889

RESUMO

Nerve cell injury associated with apoptosis plays an important role in the development of diabetic peripheral neuropathy (DPN). However, it remains unclear whether preexisting or potential neurocyte damage induced by hyperglycemia increases sensitivity to local anesthetics. SH-SY5Y cells were pretreated with a high concentration of glucose in vitro, to imitate DPN prior to administration of bupivacaine or placebo. Cell viability and apoptosis were investigated with a CCK-8 assay and flow cytometry, respectively. In addition, mitochondrial membrane potential, reactive oxygen species (ROS), mitochondrially generated ROS, and activity of mitochondrial complexes I and III were studied to explore the molecular mechanism of bupivacaine-induced mitochondrial injury. Grp78 and caspase-12 expression were measured by qRT-PCR and Western blot, representing endoplasmic reticulum (ER) stress. Cell structure was also assessed via transmission electron microscopy. Incubation with bupivacaine decreased the activity of mitochondrial complexes I and III; increased ROS production at cell and mitochondrial levels, mitochondrial potential depolarization, and Grp78 and caspase-12 expression at both transcription and translation levels; and affected cell structure, which could be enhanced by glucose pretreatment. These findings indicate that mitochondrial dysfunction and ER stress related to ROS are involved in bupivacaine-induced apoptosis and may be enhanced by glucose administration.


Assuntos
Anestésicos Locais/toxicidade , Bupivacaína/toxicidade , Estresse do Retículo Endoplasmático/fisiologia , Hiperglicemia/complicações , Neurônios/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Citometria de Fluxo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
14.
Acad Radiol ; 30(9): 1946-1961, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36567145

RESUMO

RATIONALE AND OBJECTIVES: The novel International Association for the Study of Lung Cancer (IASLC) grading system of invasive lung adenocarcinoma (ADC) demonstrated a remarkable prognostic effect and enabled numerous patients to benefit from adjuvant chemotherapy. We sought to build a CT-based nomogram for preoperative prediction of the IASLC grading. MATERIALS AND METHODS: This work retrospectively analyzed the CT images and clinical data of 303 patients with pathologically confirmed invasive ADC. The histological subtypes and radiological characteristics of the patients were re-evaluated. Radiomics features were extracted, and the optimal subset of features was established by ANOVA, spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate analyses identified the independent clinical and radiological variables. Finally, multivariate logistic regression analysis incorporated clinical, radiological, and optimal radiomics features into the nomogram. Receiver operating characteristic (ROC) curve, and accuracy were applied to assess the model's performance. Decision curve analysis (DCA), and calibration curve were applied to assess the clinical usefulness. RESULTS: Nine selected CT image features were used to develop the radiomics model. The accuracy, precision, sensitivity, and specificity of the radiomics model outperformed the clinic-radiological model in the training and testing sets. Integrating Radscore with independent radiological characteristics showed higher prediction performance than clinic-radiological characteristics alone in the training (AUC, 0.915 vs. 0.882; DeLong, p < 0.05) and testing (AUC, 0.838 vs. 0.782; DeLong, p < 0.05) sets. Good calibration and decision curve analysis demonstrated the clinical usefulness of the nomogram. CONCLUSION: Radiomics features effectively predict high-grade ADC. The combined nomogram may facilitate selecting patients who benefit from adjuvant treatment.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Gradação de Tumores , Nomogramas , Tomografia Computadorizada por Raios X , Período Pré-Operatório
15.
Phytochemistry ; 205: 113482, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36309111

RESUMO

Hyperacmotone A, a polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented skeleton, along with five undescribed congeners and eleven reported ones, was isolated from Hypericum acmosepalum. Hyperacmotone A possesses a unique monocyclic ring skeleton based on a cyclopent-4-ene-1,3-dione acylphloroglucinol core. Their structures were elucidated by extensive analysis of HRESIMS, NMR, biogenetic pathway, and quantum-chemical calculations. In addition, hypercohone G exhibited significant protective effects on high-glucose-injured HUVECs.


Assuntos
Hypericum , Humanos , Células Endoteliais , Glucose
16.
Biochim Biophys Acta Mol Cell Res ; 1870(7): 119555, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37524262

RESUMO

KIFC1, a member of kinesin-14 subfamily motors, is essential for meiotic cell division and acrosome formation during spermatogenesis. However, the functions of KIFC1 in the formation and maintenance of the acrosome in male germ cells remain to be elucidated. In this study, we report the structural deformities of acrosomes in the in vivo KIFC1 inhibition mouse models. The proacrosomal vesicles diffuse into the cytoplasm and form atypical acrosomal granules. This phenotype is consistent with globozoospermia patients and probably results from the failure of the Golgi-derived vesicle trafficking and actin filament organization. Moreover, the multinucleated and undifferentiated spermatogenic cells in the epidydimal lumen after KIFC1 inhibition reveal the specific roles of KIFC1 in regulating post-meiotic maturation. Overall, our results uncover KIFC1 as an essential regulator in the trafficking, fusion and maturation of acrosomal vesicles during spermiogenesis.

17.
Antimicrob Agents Chemother ; 56(10): 5253-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22850516

RESUMO

We previously reported a new effective therapy, continuous intrathecal amphotericin B (AMB), for the treatment of cryptococcal meningitis, which had fewer side effects and complications than conventional intrathecal AMB. In this study, the pharmacokinetics of continuous intrathecal administration and conventional intrathecal AMB were compared in rabbits, providing a pharmacokinetic basis for the use of continuous intrathecal AMB therapy. The AMB concentration in the cerebrospinal fluid (CSF), sampled via an inserted cisterna magna catheter, was determined by a liquid chromatography-tandem mass spectrometry assay. The results revealed significant pharmacokinetic differences between the two groups. In the continuous intrathecal group (0.15 mg/kg/24 h), the concentration of AMB peaked 7.01 µg/ml at 4 h and then decreased to a stable level of 1.0 to 1.34 µg/ml, with no neurological impairments, while in the conventional intrathecal group (0.015 mg/kg), the drug concentration reached a peak of 3.41 µg/ml at 1 h and then decreased progressively, with fever and neurological impairments, including convulsion and paralysis. The pharmacokinetic results indicated that the continuous intrathecal AMB is a more effective and safe therapy than the conventional intrathecal AMB, with comparatively rational pharmacokinetics and fewer neurological impairments.


Assuntos
Anfotericina B/farmacocinética , Antifúngicos/farmacocinética , Animais , Coelhos , Espaço Subaracnóideo/ultraestrutura
18.
Ophthalmic Res ; 47(2): 87-97, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21865765

RESUMO

AIM: To determine whether a diet containing excessive amounts of milk aggravates naphthalene-initiated cataracts in a common animal model of age-related human cataract. METHODS: Ninety Sprague-Dawley rats were fed a natural diet supplemented with either water (group A), normal amounts of milk (group B), excessive amounts of milk (group C), naphthalene plus water (group D), naphthalene plus normal amounts of milk (group E), naphthalene plus excessive amounts of milk (group F). Cataract development was monitored weekly using a slit lamp and lens gray value analysis. Concentrations of reactive oxygen species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) in rat lenses were measured to determine the role of oxidative stress in cataract induction. RESULTS: By week 4, the cortical gray value was significantly higher in group F than that in group D, and the cortical gray value was significantly higher in group D than in group A. However, by week 8, no significant differences were observed among groups C, F, B, E and A. ROS concentrations in lenses of rats of groups C and F were slightly higher than in those of groups B, E and A, but ROS concentrations in group F were significantly higher than in the other groups receiving naphthalene (i.e. groups D and E). GSH concentrations in group F were significantly lower than in the other groups. MDA concentrations in group F were significantly higher than in the other groups receiving naphthalene, indicating increased lipid peroxidation induced by naphthalene plus excessive intake of milk. CONCLUSIONS: Our results provide quantitative evidence that excessive intake of milk aggravates naphthalene-initiated cataracts, which is probably due to oxidative damage caused by increased ROS.


Assuntos
Catarata/induzido quimicamente , Leite/efeitos adversos , Estresse Oxidativo/fisiologia , Animais , Catarata/metabolismo , Catarata/fisiopatologia , Dieta , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Cristalino/metabolismo , Masculino , Malondialdeído/metabolismo , Naftalenos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fatores de Risco
19.
Zhonghua Yan Ke Za Zhi ; 48(10): 952-5, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23302252

RESUMO

Researches on lens proteomics are becoming prevalent in recent years. Characterized by their high resolution and efficiency, proteomics approaches provide reliable methodological support for lenses proteomic research, which demonstrates a new orientation for revealing the mechanism of cataractogenesis. This review outlines the separation, identification and some novel approaches of proteomic techniques applied in recent lenses proteomic research.


Assuntos
Catarata/metabolismo , Cristalinas/metabolismo , Cristalino/metabolismo , Proteômica/métodos , Animais , Humanos
20.
Ann Transl Med ; 10(2): 47, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282089

RESUMO

Background: This study aimed to identify potential novel therapeutic targets for nasopharyngeal carcinoma (NPC) by identifying aberrantly methylated-differentially expressed genes (DEGs) and pathways based on a comprehensive bioinformatics analysis. Methods: Eight gene expression data sets and 2 methylation microarray data sets that included NPC and control groups from the Gene Expression Omnibus were identified. Meta-analyses of the DEGs were performed using the online analysis database "NetworkAnalyst". Aberrantly methylated gene loci were obtained from the GEO2R. Aberrantly methylated DEGs were obtained from Venn diagrams. The enrichment analysis was carried out on the "Metascape" website, and the protein-protein interaction (PPI) network construction, network analysis, and visualization of the analysis results were carried out on the "String" website using "Cytoscape" software. Results: In total, 544 hypomethylation high-expression genes and 164 hypermethylation low-expression genes were obtained. The enrichment and PPI network analyses suggested that several pathways and hub genes with abnormal gene expression accompanied by methylation change, including inositol-trisphosphate 3-kinase B (ITPKB), G protein subunit beta 5 (GNB5), FYN proto-oncogene, Src family tyrosine kinase (FYN), LCK proto-oncogene, Src family tyrosine kinase (LCK), nuclear factor of activated T cells 1 (NFATC1), GNAS complex locus (GNAS), protein kinase C beta (PRKCB), zeta chain of T cell receptor associated protein kinase 70 (ZAP70), lysophosphatidic acid receptor 1 (LPAR1), protein kinase C epsilon (PRKCE), tumor protein p53 (TP53), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fibronectin 1 (FN1), cyclin D1 (CCND1), vascular endothelial growth factor A (VEGFA), HRas proto-oncogene, GTPase (HRAS), signal transducer and activator of transcription 3 (STAT3), fibroblast growth factor 2 (FGF2), amyloid beta precursor protein (APP), and matrix metallopeptidase 2 (MMP2), may be related to the occurrence of nasopharyngeal carcinoma . Conclusions: The identification of novel and important pathways and hub genes and their roles in the occurrence and development of NPC will guide clinical research and the development of pharmaceutical targets.

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