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1.
BMJ ; 385: e077890, 2024 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-38897625

RESUMEN

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.


Asunto(s)
Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Supervivencia sin Progresión , China , Metástasis de la Neoplasia
2.
Sleep ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38902934

RESUMEN

STUDY OBJECTIVES: To investigate the engagement and health outcomes of community-based intervention for obstructive sleep apnea (OSA) in the general population. METHODS: We conducted a 3-month randomized controlled trial in two communities in southern China. We initially screened the general population for high-risk OSA and further diagnosis using home sleep testing. Eligible participants were randomly (1:1) assigned to either a control or continuous positive airway pressure-based integrated intervention group. The primary outcomes were multimodal indicators reflecting health outcomes, including health-related quality of life (Short Form-36 [SF-36]), sleep-related symptoms, and cardiometabolic risk. RESULTS: Of the 2,484 participants screened, 1,423 identified as having high-risk OSA were considered for telephone invitations to participate in the trial. Of these, 401 participants responded positively (28.2%), 279 were diagnosed with OSA, and 212 were randomized. The intervention significantly improved several domains of SF-36, including physical functioning (intergroup difference, 2.8; P=0.003), vitality (2.3; P=0.031), and reported health transition (6.8; P=0.005). Sleep-related symptoms, including Epworth Sleepiness Scale (-0.7; P=0.017), Fatigue Severity Scale (-3.0; P=0.022), Insomnia Severity Index (-1.8; P<0.001), and Pittsburgh Sleep Quality Index (-0.7; P=0.032), also showed significant improvements. Although the intervention did not significantly alter glycolipid metabolism, ventricular function, or cardiac structural remodeling, it achieved a significant reduction in systolic (-4.5 mmHg; P=0.004) and diastolic blood pressure (-3.7 mmHg; P<0.001). CONCLUSIONS: Community-based intervention for previously undiagnosed OSA in the general population yielded improvements in health-related quality of life, sleep-related symptoms, and blood pressure. However, engagement in the intervention program was low.

3.
PLoS One ; 19(5): e0300316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38814894

RESUMEN

Bactrian camels inhabiting desert and semi-desert regions of China are valuable animal models for studying adaptation to desert environments and heat stress. In this study, 16S rRNA technology was employed to investigate the distribution characteristics and differences of mucosal microorganisms in the anterior gland area, posterior gland area, third gland area, cardia gland area, gastric fundic gland area and pyloric gland area of 5-peak adult healthy Bactrian camels. We aimed to explore the possible reasons for the observed microbial distribution from the aspects of histological structure and mucosal immunity. Bacteroides and Fibrobacteria accounted for 59.54% and 3.22% in the gland area, respectively, and 52.37% and 1.49% in the wrinkled stomach gland area, respectively. The gland area showed higher abundance of Bacteroides and Fibrobacteria than the wrinkled stomach gland area. Additionally, the anterior gland area, posterior gland area, third gland area, and cardia gland area of Bactrian camels mainly secreted acidic mucus, while the gastric fundic gland area mainly secreted neutral mucus and the pyloric region mainly secreted a mixture of acidic and neutral mucus. The results of immunohistochemistry techniques demonstrated that the number of IgA+ cells in the anterior glandular area, posterior glandular area, third glandular area, and cardia gland area was significantly higher than that in the fundic and pyloric gland area (p < 0.05), and the difference in IgA+ between the fundic and pyloric gland area was not significant (p > 0.05). The study revealed a large number of bacteria that can digest and degrade cellulose on the mucosa of the gastric gland area of Bactrian camels. The distribution of IgA+ cells, the structure of the mucosal tissue in the glandular region, and the composition of the mucus secreted on its surface may have a crucial influence on microbial fixation and differential distribution.


Asunto(s)
Camelus , Mucosa Gástrica , Inmunidad Mucosa , ARN Ribosómico 16S , Animales , Camelus/microbiología , Camelus/inmunología , Mucosa Gástrica/microbiología , Mucosa Gástrica/inmunología , Mucosa Gástrica/metabolismo , ARN Ribosómico 16S/genética , Bacterias/clasificación , Inmunoglobulina A/metabolismo , Masculino
4.
Immunobiology ; 229(3): 152810, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38772101

RESUMEN

BACKGROUND AND AIMS: Activation of the cGAS-STING pathway induces the production of type I interferons, initiating the antiviral immune response, which contributes to the clearance of pathogens. Previous studies have shown that STING agonists promote hepatitis B virus (HBV) clearance; however, few studies have investigated the effect of activating the cGAS-STING pathway in macrophages on HBV. METHODS: The polarization status of HBV particle-stimulated RAW264.7 macrophages was analyzed. After stimulation with HBV particles, the analysis focused on determining whether the DNA sensors in RAW264.7 macrophages recognized the viral double-stranded DNA (dsDNA) and evaluating the activation of the cGAS-STING pathway. Coculture of mouse macrophages and hepatocytes harboring HBV was used to study the antiviral activity of HBV-stimulated RAW264.7 macrophages. RESULTS: After stimulation with HBV particles, HBV relaxed circular DNA (rcDNA) was detected in RAW264.7 macrophages, and the protein expression of phospho-STING, phospho-TBK1, and phospho-IRF3 in the STING pathway was increased, as shown by Western blot analysis, which revealed that M1 polarization of macrophages was caused by increased expression of CD86. RT-PCR analyses revealed elevated expression of M1 macrophage polarization-associated cytokines such as TNFα, IL-1ß, iNOS, and IFNα/ß. In the coculture experiment, both HBsAg and HBeAg expression levels were significantly decreased in AML12-HBV1.3 cells cocultured with the supernatants of HBV-stimulated RAW264.7 macrophages. CONCLUSION: The results suggest that macrophages can endocytose HBV particles. Additionally, viral dsDNA can be recognized by DNA pattern recognition receptors, which in turn activate the cGAS-STING pathway, promoting the M1 polarization of macrophages, while no significant M2 polarization is observed. Macrophages stimulated with HBV particles exhibit enhanced antiviral activity against HBV.


Asunto(s)
ADN Viral , Virus de la Hepatitis B , Macrófagos , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/inmunología , Animales , Nucleotidiltransferasas/metabolismo , Ratones , Macrófagos/inmunología , Macrófagos/virología , Macrófagos/metabolismo , Proteínas de la Membrana/metabolismo , Células RAW 264.7 , Hepatitis B/inmunología , Hepatitis B/virología , Humanos , Activación de Macrófagos/inmunología , Hepatocitos/virología , Hepatocitos/inmunología , Hepatocitos/metabolismo , Factor 3 Regulador del Interferón/metabolismo
5.
Int Immunopharmacol ; 134: 112219, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38733823

RESUMEN

BACKGROUNDS & AIMS: Given its ability to inhibit HBV replication, Interferon alpha (IFN-α) treatment has been confirmed to be effective in managing Chronic Hepatitis B (CHB). However, its underlying mechanisms are incompletely understood. METHODS: Herein, we investigated the antiviral properties of IFN-α by introducing IFN-α expression plasmids into a well-established HBV Hydrodynamic Injection (HDI) mouse model and examined the impact of IFN-α or hepcidin treatment on macrophages derived from THP-1 cells. The cytokine profiles were analyzed using the cytometry microsphere microarray technology, and flow cytometry was used to analyze the polarization of macrophages. Additionally, the IL-6/JAK2/STAT3 signaling pathway and the hepcidin-ferroportin axis were analyzed to better understand the macrophage polarization mechanism. RESULTS: As evidenced by the suppression of HBV replication, injection of an IFN-α expression plasmid and supernatants of IFN-α-treated macrophages exerted anti-HBV effects. The IFN-α treatment up-regulated IL-6 in mice with HBV replication, as well as in IFN-α-treated HepG2 cells and macrophages. Furthermore, JAK2/STAT3 signaling and hepcidin expression was promoted, inducing iron accumulation via the hepcidin-ferroportin axis, which caused the polarization of M1 macrophages. Furthermore, under the effect of IFN-α, IL-6 silencing or blockade downregulated the JAK2/STAT3 signaling pathway and hepcidin, implying that increased hepcidin expression under IFN-α treatment was dependent on the IL-6/JAK2/STAT3 pathway. CONCLUSION: The IL-6/JAK2/STAT3 signaling pathway is activated by IFN-α which induces hepcidin expression. The resulting iron accumulation then induces the polarization of M1 macrophages via the hepcidin-ferroportin axis, yielding an immune response which exerts antiviral effects against HBV replication.


Asunto(s)
Antivirales , Virus de la Hepatitis B , Hepcidinas , Interferón-alfa , Janus Quinasa 2 , Macrófagos , Factor de Transcripción STAT3 , Hepcidinas/metabolismo , Hepcidinas/genética , Animales , Humanos , Interferón-alfa/farmacología , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Virus de la Hepatitis B/fisiología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Antivirales/farmacología , Antivirales/uso terapéutico , Ratones , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Células Hep G2 , Transducción de Señal/efectos de los fármacos , Interleucina-6/metabolismo , Células THP-1 , Ratones Endogámicos C57BL , Replicación Viral/efectos de los fármacos , Masculino , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Modelos Animales de Enfermedad , Hepatitis B/inmunología , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética
6.
Artículo en Inglés | MEDLINE | ID: mdl-38466605

RESUMEN

The nature of heterophilous graphs is significantly different from that of homophilous graphs, which causes difficulties in early graph neural network (GNN) models and suggests aggregations beyond the one-hop neighborhood. In this article, we develop a new way to implement multiscale extraction via constructing Haar-type graph framelets with desired properties of permutation equivariance, efficiency, and sparsity, for deep learning tasks on graphs. We further design a graph framelet neural network model permutation equivariant graph framelet augmented network (PEGFAN) based on our constructed graph framelets. The experiments are conducted on a synthetic dataset and nine benchmark datasets to compare the performance with other state-of-the-art models. The result shows that our model can achieve the best performance on certain datasets of heterophilous graphs (including the majority of heterophilous datasets with relatively larger sizes and denser connections) and competitive performance on the remaining.

7.
J Colloid Interface Sci ; 664: 251-262, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38467090

RESUMEN

Ruthenium (Ru) nanoparticles dispersed on carbon support are promising electrocatalysts for hydrogen evolution reaction (HER) due to strong electronic metal-carbon interactions (EMCIs). Defects engineering in carbon supports is an effective strategy to adjust EMCIs. We prepared nitrogen/sulfur co-doped carbon supported Ru nanoparticles (Ru@N/S-LC) using sodium lignosulfonate and urea as feedstocks. Intrinsic S dopants from sodium lignosulfonate create rich S defects, thus enhancing the EMCIs within Ru@N/S-LC, leading a faster electron transfer between Ru nanoparticles and N/S-LC compared with N-doped carbon supported Ru nanoparticles (Ru@N-CC). The resulting Ru@N/S-LC exhibits an enhanced work function and a down-shifted d-band center, inducing stronger electron capturing ability and weaker hydrogen desorption energy than Ru@N-CC. Ru@N/S-LC requires only 7 and 94 mV overpotential in acidic medium and alkaline medium to achieve a current density of 10 mA cm-2. Density Functional Theory (DFT) calculations were utilized to clarify the impact of sulfur (S) doping and the mechanism underlying the notable catalytic activity of Ru@N/S-LC. This study offers a perspective for utilizing the natural dopants of biomass to adjust the EMCIs for electrocatalysts.

8.
Aging Cell ; 23(5): e14121, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38450924

RESUMEN

Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of genome instability linked to AD pathogenesis remain poorly understood. Here, we report the first characterization of the age- and sex-related trajectories of telomere length (TL) and micronuclei in APP/PS1 mice model and wild-type (WT) controls (C57BL/6). TL was measured in brain (prefrontal cortex, cerebellum, pituitary gland, and hippocampus), colon and skin, and MN was measured in bone marrow in 6- to 14-month-old mice. Variation in TL was attributable to tissue type, age, genotype and, to a lesser extent, sex. Compared to WT, APP/PS1 had a significantly shorter baseline TL across all examined tissues. TL was inversely associated with age in both genotypes and TL shortening was accelerated in brain of APP/PS1. Age-related increase of micronuclei was observed in both genotypes but was accelerated in APP/PS1. We integrated TL and micronuclei data with data on cognition performance and brain amyloidosis. TL and micronuclei were linearly correlated with cognition performance or Aß40 and Aß42 levels in both genotypes but to a greater extent in APP/PS1. These associations in APP/PS1 mice were dominantly driven by females. Together, our findings provide foundational knowledge to infer the TL and micronuclei trajectories in APP/PS1 mice during disease progression, and strongly support that TL attrition and micronucleation are tightly associated with AD pathogenesis in a female-biased manner.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Disfunción Cognitiva , Modelos Animales de Enfermedad , Ratones Transgénicos , Animales , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Ratones , Amiloidosis/patología , Amiloidosis/metabolismo , Amiloidosis/genética , Femenino , Disfunción Cognitiva/patología , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Masculino , Encéfalo/patología , Encéfalo/metabolismo , Telómero/metabolismo , Telómero/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Caracteres Sexuales , Ratones Endogámicos C57BL , Presenilina-1/genética , Presenilina-1/metabolismo , Micronúcleos con Defecto Cromosómico
9.
J Environ Manage ; 357: 120597, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38552510

RESUMEN

Graphitic carbon nitride (g-C3N4) is a promising metal-free photocatalyst; however, its high carrier recombination rate and insufficient redox capacity limit its degradation effect on antibiotics. In order to overcome these shortcomings, the photocatalytic activity is improved by regulating the spin polarization state, constructing the internal electric field, and applying the external piezoelectric field. In this paper, the chlorine-doped and nitrogen-deficient porous carbon nitride composite carbon quantum dots (Nv-Cl/UPCN@CQD) has been synthesized successfully. The doping position of chlorine and spin polarization properties are verified by DFT calculation. The key intermediates *O2- and *OOH for the synthesis of reactive oxygen species were detected by in-situ infrared testing, which promotes the production of •O2- and H2O2. The degradation rate constant of Nv-Cl/UPCN@CQD for removal of tetracycline is 8.45 times higher than that of g-C3N4. The active oxygen production and degradation efficiency of piezoelectric photocatalysis under the synergistic effect of intense stirring and vis-light irradiation are much higher than those of photocatalysis and piezoelectric catalysis, and the conversion of H2O2 to •OH is promoted by piezoelectric field. This paper provides a reliable way to improve the performance of piezoelectric photocatalysts by adjusting their energy band, electronic structure and piezoelectric force.


Asunto(s)
Cloro , Puntos Cuánticos , Peróxido de Hidrógeno , Antibacterianos , Nitrógeno , Puntos Cuánticos/química , Catálisis
10.
J Food Sci ; 89(1): 259-275, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37983838

RESUMEN

This study explores the multifaceted attributes of black soldier fly larvae protein (BSFLP), focusing on its physicochemical, functional, and antioxidant properties. BSFLP is characterized by 16 amino acids, with a predominant random coil secondary structure revealed by circular dichroism spectra. Differential scanning calorimetry indicates a substantial thermal denaturation temperature of 97.63°C. The protein exhibits commendable solubility, emulsification, and foaming properties in alkaline and low-salt environments, albeit with reduced water-holding capacity and foam stability under elevated alkaline and high-temperature conditions. In vitro assessments demonstrate that BSFLP displays robust scavenging proficiency against 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radicals, with calculated EC50 values of 1.90 ± 0.57, 0.55 ± 0.01, and 1.14 ± 0.02 mg/mL, respectively, along with notable reducing capabilities. Results from in vivo antioxidant experiments reveal that BSFLP, administered at doses of 300 and 500 mg/kg, significantly enhances the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) (p < 0.05) while simultaneously reducing malondialdehyde levels in both serum and tissues of d-galactose-induced oxidative stress in mice. Moreover, the protein effectively attenuates oxidative damage in liver and hippocampal tissues. These findings underscore the potential utility of BSFLP as a natural antioxidant source, with applications spanning the food, pharmaceutical, and cosmetic industries. PRACTICAL APPLICATION: Black soldier fly larvae protein emerges as an environmentally sustainable reservoir of natural antioxidants, holding significant promise for the food, pharmaceutical, and cosmetic sectors. Its advantageous amino acid composition, robust thermal resilience, and impressive functional attributes position it as a compelling subject for continued investigation and advancement in various applications.


Asunto(s)
Antioxidantes , Dípteros , Animales , Ratones , Antioxidantes/química , Larva , Dípteros/metabolismo , Estrés Oxidativo , Extractos Vegetales/química
11.
Chin Med J (Engl) ; 136(22): 2706-2711, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37882066

RESUMEN

BACKGROUND: Distinguishing between primary clear cell carcinoma of the liver (PCCCL) and common hepatocellular carcinoma (CHCC) through traditional inspection methods before the operation is difficult. This study aimed to establish a Faster region-based convolutional neural network (RCNN) model for the accurate differential diagnosis of PCCCL and CHCC. METHODS: In this study, we collected the data of 62 patients with PCCCL and 1079 patients with CHCC in Beijing YouAn Hospital from June 2012 to May 2020. A total of 109 patients with CHCC and 42 patients with PCCCL were randomly divided into the training validation set and the test set in a ratio of 4:1.The Faster RCNN was used for deep learning of patients' data in the training validation set, and established a convolutional neural network model to distinguish PCCCL and CHCC. The accuracy, average precision, and the recall of the model for diagnosing PCCCL and CHCC were used to evaluate the detection performance of the Faster RCNN algorithm. RESULTS: A total of 4392 images of 121 patients (1032 images of 33 patients with PCCCL and 3360 images of 88 patients with CHCC) were uesd in test set for deep learning and establishing the model, and 1072 images of 30 patients (320 images of nine patients with PCCCL and 752 images of 21 patients with CHCC) were used to test the model. The accuracy of the model for accurately diagnosing PCCCL and CHCC was 0.962 (95% confidence interval [CI]: 0.931-0.992). The average precision of the model for diagnosing PCCCL was 0.908 (95% CI: 0.823-0.993) and that for diagnosing CHCC was 0.907 (95% CI: 0.823-0.993). The recall of the model for diagnosing PCCCL was 0.951 (95% CI: 0.916-0.985) and that for diagnosing CHCC was 0.960 (95% CI: 0.854-0.962). The time to make a diagnosis using the model took an average of 4 s for each patient. CONCLUSION: The Faster RCNN model can accurately distinguish PCCCL and CHCC. This model could be important for clinicians to make appropriate treatment plans for patients with PCCCL or CHCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Carcinoma Hepatocelular/patología , Redes Neurales de la Computación
12.
Am J Transl Res ; 15(9): 5730-5746, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37854219

RESUMEN

OBJECTIVE: Acute kidney injury (AKI) is a global problem due to its high morbidity and mortality. The aim of this study was to identify the key RNAs involved in the ischemia/reperfusion (I/R) or cisplatin (CIS) induced AKI. METHODS: Gene Expression Omnibus database was used to download the microarray dataset GSE106993, GSE130814 and GSE98622. Differentially expressed lncRNAs (DE-lncRNAs) and DE-mRNAs were identified in I/R and CIS induced AKI. The target miRNAs of DE lncRNAs were predicted from miRDB, and the miRNA of lncRNA target mRNAs were predicted form StarBase dataset. The ceRNA regulatory networks, GO and KEGG enrichment analysis, and protein-protein interaction (PPI) of I/R and CIS induced AKI specific genes were constructed. The CIBESORT was applied to infer the proportion of 22 immune infiltration cells based on gene expression profiles of I/R and CIS induced AKI. RESULTS: Totally, 2 DE-lncRNAs and 375 DE-mRNAs were identified in I/R and CIS induced AKI. The common ceRNA network was constructed between CIS group and I/R induced AKI group, which contained 2 lncRNAs (Platr7 and Gm15611), 65 mmu-miRNAs and 167 mRNAs. The 167 common mRNAs were enriched in the biological process of transcription regulation, metabolic process, cell proliferation, the cellular component (CC) of extracellular region and space, the molecular function of DNA binding, and transcription regulator activity in CIS and IRI induced AKI. The common 167 mRNAs involved in the MAPK signaling pathway and JAK-STAT signaling pathway were identified. Protein-Protein Interaction (PPI) Network of ceRNAs network expressed gene was constructed, including 81 nodes, which contained 3 upregulated genes and 78 downregulated genes. Among them, mitochondrial apoptosis-related genes Pmaip1 and Nptx1 showed significantly high expression in the GSE98622 and GSE106993 data sets. The investigation to the connection between the gene expression profiles and immune cell infiltration showed considerable differences in immune cell percentage between AKI group and normal group. CONCLUSION: Novel lncRNAs and mRNAs were identified, which may serve as potential biomarkers to predict the diagnostic and therapeutic targets for AKI patients based on a large-scale sample. More importantly, the ceRNA network of I/R or CIS induced AKI was constructed, which provides valuable information to further explore the molecular mechanism underlying onset and progression of AKI.

13.
Front Oncol ; 13: 1152622, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37727213

RESUMEN

This study summarizes the latest achievements, challenges, and future research directions in deep learning technologies for the diagnosis of renal cell carcinoma (RCC). This is the first review of deep learning in RCC applications. This review aims to show that deep learning technologies hold great promise in the field of RCC diagnosis, and we look forward to more research results to meet us for the mutual benefit of renal cell carcinoma patients. Medical imaging plays an important role in the early detection of renal cell carcinoma (RCC), as well as in the monitoring and evaluation of RCC during treatment. The most commonly used technologies such as contrast enhanced computed tomography (CECT), ultrasound and magnetic resonance imaging (MRI) are now digitalized, allowing deep learning to be applied to them. Deep learning is one of the fastest growing fields in the direction of medical imaging, with rapidly emerging applications that have changed the traditional medical treatment paradigm. With the help of deep learning-based medical imaging tools, clinicians can diagnose and evaluate renal tumors more accurately and quickly. This paper describes the application of deep learning-based imaging techniques in RCC assessment and provides a comprehensive review.

14.
Nanoscale ; 15(38): 15717-15729, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37728399

RESUMEN

The accumulation of amyloid-ß (Aß) into senile plaques and the resulting continuous oxidative stress are major pathogenic mechanisms in Alzheimer's disease (AD). In this study, we designed a lipoprotein-inspired nanoparticle to facilitate Aß clearance and alleviate oxidative stress for the treatment of AD. Lipoprotein-like nanocomposites (RLA-rHDL@ANG) were fabricated by assembling reconstituted high density lipoprotein (rHDL) with an apoE-derived peptide (RLA) with Aß binding and clearance capabilities, and were subsequently camouflaged using reactive oxygen species (ROS)-sensitive DSPE-TK-mPEG2000 and DSPE-TK-PEG3400-ANG with brain penetration as well as ROS scavenging ability. Immunoelectron microscopy, fluorescence colocalization, and enzyme linked immunosorbent assay, together with a thioflavin-T (ThT) fluorescence quantitative test, showed that RLA-rHDL@ANG possessed the ability of high binding affinity to both Aß monomers and oligomers, and disintegration of pre-formed Aß aggregates. ROS level monitoring and transmission electron microscopy (TEM) showed that RLA-rHDL@ANG possessed ROS sensitivity and consumption properties. Transcellular assay and in vivo imaging showed that RLA-rHDL@ANG effectively facilitated blood-brain barrier (BBB) penetration and intracerebral accumulation. It promoted the efficient degradation of Aß by microglia and neurons through lysosomal transport and elimination approaches. Four-week administration of RLA-rHDL@ANG effectively reduced Aß deposition, decreased the ROS level and improved cognitive functions in AD mice. These findings indicate that multifunctional RLA-rHDL@ANG may serve as a promising and feasible candidate for managing the progression of AD.

15.
World J Clin Cases ; 11(14): 3167-3175, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37274032

RESUMEN

BACKGROUND: The incidence of lumbar tuberculosis is high worldwide, and effective treatment is a continuing problem. AIM: To study the safety and efficacy of the multitrack and multianchor point screw technique combined with the contralateral Wiltse approach for lesion debridement to treat lumbar tuberculosis. METHODS: The C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) score, oswestry disability index (ODI) and American Spinal Injury Association (ASIA) grade were recorded and analysed pre- and postoperatively. RESULTS: The CRP level and ESR returned to normal, and the VAS score and ODI were decreased at 3 mo postoperatively, with significant differences compared with the preoperative values (P < 0.01). Neurological dysfunction was relieved, and the ASIA grade increased, with no adverse events. CONCLUSION: The multitrack, multianchor point screw fixation technique combined with the contralateral Wiltse approach for debridement is an effective and safe method for the treatment of lumbar tuberculosis.

16.
Ann Clin Lab Sci ; 53(2): 192-199, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37094847

RESUMEN

OBJECTIVE: The dysfunction of mesangial cells is a key contributor to the pathogenesis of diabetic nephropathy, while the underlying molecular basis is not fully elucidated. METHODS: Mouse mesangial cells were administered with high glucose medium and the expression of polo-like kinase 2 (PLK2) was determined by PCR and western blot. Loss-of- and gain-of-function of PLK2 was achieved by small interfering RNA targeting PLK2 or PLK2 overexpression plasmid transfections. The hypertrophy, extracellular matrix production, and oxidative stress of mesangial cells were detected. The activation of p38-MAPK signaling was tested using western blot. SB203580 was employed to block the p38-MAPK signaling. The expression of PLK2 in human renal biopsies was detected by immunohistochemistry. RESULTS: High glucose administration upregulated the expression of PLK2 in mesangial cells. PLK2 knockdown reversed the hypertrophy, extracellular matrix production, and oxidative stress induced by high glucose in mesangial cells. PLK2 knockdown suppressed the activation of p38-MAPK signaling. Blockade of p38-MAPK signaling by SB203580 abolished the dysfunction of mesangial cells induced by high glucose and PLK2 overexpression. The enhanced expression of PLK2 was validated in human renal biopsies. CONCLUSION: PLK2 is a key participant in high glucose-induced mesangial cell dysfunction, and might play a crucial role in the pathogenesis of diabetic nephropathy.


Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Humanos , Ratones , Animales , Células Mesangiales/metabolismo , Células Mesangiales/patología , Transducción de Señal , Glucosa/metabolismo , Estrés Oxidativo , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Hipertrofia/metabolismo , Hipertrofia/patología
17.
Sensors (Basel) ; 23(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37112388

RESUMEN

Addressing the problem that control methods of wheel-legged robots for future Mars exploration missions are too complex, a time-efficient control method based on velocity planning for a hexapod wheel-legged robot is proposed in this paper, which is named time-efficient control based on velocity planning (TeCVP). When the foot end or wheel at knee comes into contact with the ground, the desired velocity of the foot end or knee is transformed according to the velocity transformation of the rigid body from the desired velocity of the torso which is obtained by the deviation of torso position and posture. Furthermore, the torques of joints can be obtained by impedance control. When suspended, the leg is regarded as a system consisting of a virtual spring and a virtual damper to realize control of legs in the swing phase. In addition, leg sequences of switching motion between wheeled configuration and legged configuration are planned. According to a complexity analysis, velocity planning control has lower time complexity and less times of multiplication and addition compared with virtual model control. In addition, simulations show that velocity planning control can realize stable periodic gait motion, wheel-leg switching motion and wheeled motion and the operation time of velocity planning control is about 33.89% less than that of virtual model control, which promises a great prospect for velocity planning control in future planetary exploration missions.

18.
Front Pediatr ; 11: 1060053, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36846163

RESUMEN

Backgrounds & aims: Epstein-Barr virus (EBV) infection occurs commonly in children and may cause acute infectious mononucleosis (AIM) and various malignant diseases. Host immune responses are key players in the resistance to EBV infection. We here assessed the immunological events and laboratory indicators of EBV infection, as well as determined the clinical usefulness of evaluating the severity and efficacy of antiviral therapy in AIM patients. Methods: We enrolled 88 children with EBV infection. The immune environment was defined by immunological events such as frequencies of lymphocyte subsets, phenotypes of T cells, and their ability to secrete cytokines, and so on. This environment was analyzed in EBV-infected children with different viral loads and in children in different phases of infectious mononucleosis (IM) from disease onset to convalescence. Results: Children with AIM had higher frequencies of CD3+ T and CD8+ T cells, but lower frequencies of CD4+ T cells and CD19+ B cells. In these children, the expression of CD62L was lower and that of CTLA-4 and PD-1 was higher on T cells. EBV exposure induced granzyme B expression, but reduced IFN-γ secretion, by CD8+ T cells, whereas NK cells exhibited reduced granzyme B expression and increased IFN-γ secretion. The frequency of CD8+ T cells was positively correlated with the EBV DNA load, whereas the frequencies of CD4+ T cells and B cells were negatively correlated. During the convalescent phase of IM, CD8+ T cell frequency and CD62L expression on T cells were restored. Moreover, patient serum levels of IL-4, IL-6, IL-10, and IFN-γ were considerably lower throughout the convalescent phase than throughout the acute phase. Conclusion: Robust expansion of CD8+ T cells, accompanied by CD62L downregulation, PD-1 and CTLA-4 upregulation on T cells, enhanced granzyme B production, and impaired IFN-γ secretion, is a typical characteristic of immunological events in children with AIM. Noncytolytic and cytolytic effector functions of CD8+ T cells are regulated in an oscillatory manner. Furthermore, the AST level, number of CD8+ T cells, and CD62L expression on T cells may act as markers related to IM severity and the effectiveness of antiviral treatment.

19.
Molecules ; 28(3)2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36770732

RESUMEN

Insulating oil plays a crucial role in internal insulation of oil-impregnated transformers. It has been demonstrated in a variety of experimental studies that mineral oil (MO) and vegetable oil (VO) can be blended in different ratios to improve insulation properties; however, the mechanisms underlying this phenomenon remain unclear. In this study, a molecular dynamics (MD) simulation approach was used to investigate diffusion of water molecules in VO/MO blends and dielectric constants of a mixture. The results show that the diffusion coefficient of water molecules is negatively correlated with the proportion of VO; thus, addition of VO helps to improve the insulation properties of a mixture. Due to introduction of strong polar functional groups, a decrease in the diffusion behavior of water molecules can be attributed to an increase in the interaction energy and formation of hydrogen bonds between water molecules and the mixed oil system. There is a direct correlation between the dielectric constant of a mixture and VO content; however, it is very sensitive to water content. The presence of strong polar water molecules or functional groups in a mixture leads to an increase in the dielectric constant, which results in a reduction in insulating properties. Accordingly, presence of polar groups plays an important role in determining the insulating properties of a mixture. To increase the insulation performance of a mixture, it is important to consider the diffusion-inhibiting and dielectric effects of the stronger polar groups in vegetable oil compared to those in mineral oil.

20.
Neural Netw ; 156: 135-151, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36257070

RESUMEN

To develop an efficient brain-computer interface (BCI) system, electroencephalography (EEG) measures neuronal activities in different brain regions through electrodes. Many EEG-based motor imagery (MI) studies do not make full use of brain network topology. In this paper, a deep learning framework based on a modified graph convolution neural network (M-GCN) is proposed, in which temporal-frequency processing is performed on the data through modified S-transform (MST) to improve the decoding performance of original EEG signals in different types of MI recognition. MST can be matched with the spatial position relationship of the electrodes. This method fusions multiple features in the temporal-frequency-spatial domain to further improve the recognition performance. By detecting the brain function characteristics of each specific rhythm, EEG generated by imaginary movement can be effectively analyzed to obtain the subjects' intention. Finally, the EEG signals of patients with spinal cord injury (SCI) are used to establish a correlation matrix containing EEG channel information, the M-GCN is employed to decode relation features. The proposed M-GCN framework has better performance than other existing methods. The accuracy of classifying and identifying MI tasks through the M-GCN method can reach 87.456%. After 10-fold cross-validation, the average accuracy rate is 87.442%, which verifies the reliability and stability of the proposed algorithm. Furthermore, the method provides effective rehabilitation training for patients with SCI to partially restore motor function.


Asunto(s)
Interfaces Cerebro-Computador , Traumatismos de la Médula Espinal , Humanos , Reproducibilidad de los Resultados , Electroencefalografía/métodos , Movimiento/fisiología , Algoritmos , Traumatismos de la Médula Espinal/diagnóstico , Imaginación/fisiología
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