Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.491
Filtrar
1.
Am J Epidemiol ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965751

RESUMO

This study assessed the quality of cause-of-death reporting in the US before and during the COVID-19 pandemic. We used the selection rate and the adjusted odds ratio (aOR) to analyze each cause identified by the National Center for Health Statistics as unsuitable for the underlying cause of death (UCOD). The selection rate was defined as the proportion of deaths with mention of a particular unsuitable UCOD on the death certificate where that cause was ultimately selected as the UCOD. Out of 36 unsuitable UCODs, 33 exhibited a significant decline in selection rates from 2019 to 2021. However, when deaths with mention of COVID-19 on the death certificate were excluded, only 19 causes revealed a significant decline. In analyses that controlled for the age of decedents, aORs in 2021 were significantly lower compared with 2019 for 26 causes, and this number decreased to 17 causes in analyses that excluded COVID-19-related deaths. In conclusion, the overall quality of COD reporting improved during the COVID-19 pandemic, attributable mainly to the fact that over one-tenth of the deaths were related to COVID-19. Yet, for deaths that did not involve COVID-19, improvements in the quality of COD reporting were less prominent for certain causes.

2.
World J Gastrointest Oncol ; 16(6): 2335-2349, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994128

RESUMO

As a highly aggressive tumor, the pathophysiological mechanism of primary liver cancer has attracted much attention. In recent years, factors such as ferroptosis regulation, lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer, providing a new perspective for understanding the development of liver cancer. Ferroptosis regulation, lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer. The regulation of ferroptosis is involved in apoptosis and necrosis, affecting cell survival and death. Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells. Metabolic abnormalities, especially the disorders of glucose and lipid metabolism, directly affect the proliferation and growth of liver cancer cells. Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes. The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer, and reduce the risk of disease by adjusting the metabolic process. This review focuses on the key roles of ferroptosis regulation, lipid peroxidation and metabolic abnormalities in this process.

3.
BMC Plant Biol ; 24(1): 681, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39020275

RESUMO

BACKGROUND: A retrotransposon HORT1 in the promoter of the anthocyanin activator gene PeMYB11, microRNA858 (miR858) that targets PeMYB11, and a repressor PeMYBx have been implicated in pigmentation patterning diversity of harlequin Phalaenopsis orchids. However, the interrelationship among them remains to be elucidated. RESULTS: To understand how these factors interact to generate anthocyanin spots in Phalaenopsis, we successfully developed a mathematical model based on the known reaction-diffusion system to simulate their interplay and refined the conceptual biological model. Intriguingly, the expression of both PeMYBx and PeMYB11 were in phase for purple spot formation, even though they showed adverse effects on anthocyanin accumulations. An increase in the self-activation rate of PeMYB11 resulted in the increased size of purple spots, but no effects on spot fusion. Decreased degradation rate of miR858 in the purple regions, led to disruption of the formation of spotted pigmentation patterning and a full-red pigmentation pattern. Significantly, the reduced miR858 level promotes the fusion of large dark purple dots induced by the solo-LTR of HORT1, eventually generating the purple patches. In addition, the spatially heterogeneous insertion of HORT1 caused by the remnant solo-LTR of HORT1 derived from random homologous unequal recombination of HORT1 in individual cells of floral organs could explain the diverse pigmentation patterning of harlequin Phalaenopsis. CONCLUSIONS: This devised model explains how HORT1 and miR858 regulate the formation of the pigmentation patterning and holds great promise for developing efficient and innovative approaches to breeding harlequin Phalaenopsis orchids.


Assuntos
Orchidaceae , Pigmentação , Orchidaceae/genética , Orchidaceae/metabolismo , Pigmentação/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , MicroRNAs/metabolismo , Antocianinas/metabolismo , Simulação por Computador , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Retroelementos/genética
4.
Cell Chem Biol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39025070

RESUMO

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39027976

RESUMO

Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.

6.
Sci Rep ; 14(1): 15331, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961200

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.


Assuntos
Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/imunologia , Células Hep G2 , Inibidores de PCSK9 , Ressonância de Plasmônio de Superfície , Receptores de LDL/metabolismo , Epitopos/imunologia , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/imunologia
8.
Commun Biol ; 7(1): 895, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39043865

RESUMO

Staphylococcus aureus signal peptidase IB (SpsB) is an essential enzyme for protein secretion. While inhibition of its activity by small molecules is a well-precedented mechanism to kill bacteria, the mode of activation is however less understood. We here investigate the activation mechanism of a recently introduced activator, the antibiotic compound PK150, and demonstrate by combined experimental and Molecular Dynamics (MD) simulation studies a unique principle of enzyme stimulation. Mass spectrometric studies with an affinity-based probe of PK150 unravel the binding site of PK150 in SpsB which is used as a starting point for MD simulations. Our model shows the localization of the molecule in an allosteric pocket next to the active site which shields the catalytic dyad from excess water that destabilizes the catalytic geometry. This mechanism is validated by the placement of mutations aligning the binding pocket of PK150. While the mutants retain turnover of the SpsB substrate, no stimulation of activity is observed upon PK150 addition. Overall, our study elucidates a previously little investigated mechanism of enzyme activation and serves as a starting point for the development of future enzyme activators.


Assuntos
Proteínas de Bactérias , Simulação de Dinâmica Molecular , Serina Endopeptidases , Staphylococcus aureus , Staphylococcus aureus/enzimologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Ativação Enzimática , Sítios de Ligação , Antibacterianos/farmacologia , Domínio Catalítico
10.
Macromol Rapid Commun ; : e2400245, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012277

RESUMO

Advancements in flexible electronic technology, especially the progress in foldable displays and under-display cameras (UDC), have created an urgent demand for high-performance colorless polyimide (CPI). However, current CPIs lack sufficient heat resistance for substrate applications. In this work, four kinds of rigid spirobifluorene diamines are designed, and the corresponding polyimides are prepared by their condensation with 5,5'-(perfluoropropane-2,2-diyl) bis(isobenzofuran-1,3-dione) (6FDA) or 9,9-bis(3,4-dicarboxyphenyl) fluorene dianhydride (BPAF). The rigid and conjugated spirobifluorene units endow the polyimides with higher glass transition temperature (Tg) ranging from 356 to 468 °C. Their optical properties are regulated by small side groups and spirobifluorene structure with a periodically twisted molecular conformation. Consequently, a series of CPIs with an average transmittance ranging from 75% to 88% and a yellowness index (YI) as low as 2.48 are obtained. Among these, 27SPFTFA-BPAF presents excellent comprehensive performance, with a Tg of 422 °C, a 5 wt.% loss temperature (Td5) of 562 °C, a YI of 3.53, and a tensile strength (δmax) of 140 MPa, respectively. The mechanism underlying the structure-property relationship is investigated by experimental comparison and theoretical calculation, and the proposed method provides a pathway for designing highly rigid conjugated CPIs with excellent thermal stability and transparency for photoelectric engineering.

11.
J Am Chem Soc ; 146(28): 18841-18847, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38975938

RESUMO

An asymmetric intramolecular spiro-amination to high steric hindering α-C-H bond of 1,3-dicarbonyl via nitrene transfer using inactive aryl azides has been carried out by developing a novel Cp*Ir(III)-SPDO (spiro-pyrrolidine oxazoline) catalyst, thereby enabling the first successful construction of structurally rigid spiro-quaternary indolinone cores with moderate to high yields and excellent enantioselectivities. DFT computations support the presence of double bridging H-F bonds between [SbF6]- and both the ligand and substrate, which favors the plane-differentiation of the enol π-bond for nitrenoid attacking. These findings open up numerous opportunities for the development of new asymmetric nitrene transfer systems.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39013587

RESUMO

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

13.
PLoS One ; 19(7): e0305213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954712

RESUMO

BACKGROUND AND AIM: Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. METHODS: We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. RESULTS: Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. CONCLUSION: Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.


Assuntos
Hipotermia Induzida , Fígado , Traumatismo por Reperfusão , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/terapia , Animais , Hipotermia Induzida/métodos , Fígado/patologia , Camundongos , Ratos , Modelos Animais de Doenças
14.
J Spec Pediatr Nurs ; 29(3): e12435, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39032153

RESUMO

PURPOSE: This study aimed to examine determinants of undernutrition among children under 2 years of age. DESIGN AND METHODS: A matched case-control study design was conducted to recruit 300 mothers comprising 100 mothers with an undernourished child (case group) and 200 mothers with a healthy child (control group). Measurements consisted of demographic characteristics of children data, mother's data, household data, mother's knowledge of child undernutrition, mother's knowledge of nutrition, complementary feeding practices, and undernutrition parameters of the children. A conditional logistic regression was used to identify determinants of undernutrition. The risk of undernutrition was estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Statistical significance was defined as any p value of <.05. RESULTS: Findings showed that mother's knowledge of undernutrition (AOR: 0.95; 95% CI: 0.91-0.98), mother's knowledge of nutrition (AOR: 0.90; 95% CI: 0.85-0.96), and mother's knowledge (AOR: 0.78; 95% CI: 0.67-0.91) and behavior of complementary feeding practices (AOR: 0.97; 95% CI: 0.94-0.99) were significant determinants of undernutrition (p < .05). PRACTICE IMPLICATIONS: Mothers with high scores on knowledge of undernutrition, knowledge of nutrition, and knowledge and behaviors of complementary feeding practices would benefit the children under 2 years to reduce the risk of undernutrition. Healthcare professionals (i.e., pediatric nurses and community health nurses) should provide early assessment of knowledge related to undernutrition, nutrition, and complementary feeding practices for mothers with children under 2 years.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Desnutrição , Mães , Humanos , Feminino , Estudos de Casos e Controles , Lactente , Masculino , Mães/estatística & dados numéricos , Mães/psicologia , Adulto , Desnutrição/epidemiologia , Pré-Escolar , Transtornos da Nutrição Infantil/epidemiologia , Fatores de Risco , Estado Nutricional
15.
Org Lett ; 26(27): 5657-5663, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38941517

RESUMO

A protocol for the electrooxidative [3+2] annulation to generate indolo[2,3-b]indoles in an undivided cell is reported. It exhibits good yields with excellent regioselectivities and tolerates various functional groups without external chemical oxidants. Cyclic voltammetry and density functional theory calculations indicate that the [3+2] annulation is initiated by the simultaneous anodic oxidation of indole and aniline derivatives, and the step to determine the rate relies on the combination of radical cations.

16.
Int J Biol Macromol ; 273(Pt 1): 133035, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866276

RESUMO

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Polissacarídeos , Transdução de Sinais , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Estresse Oxidativo/efeitos dos fármacos , Masculino , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Galactose , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/induzido quimicamente
17.
Vaccines (Basel) ; 12(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38932387

RESUMO

BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

18.
PLoS One ; 19(6): e0298484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837988

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Furthering insights into patients' ADPKD progression could lead to earlier detection, management, and alter the course to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. A retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using differences in eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. Among 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. Using real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.


Assuntos
Progressão da Doença , Taxa de Filtração Glomerular , Rim Policístico Autossômico Dominante , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Rim/fisiopatologia , Rim/patologia , Falência Renal Crônica/epidemiologia
19.
Front Pharmacol ; 15: 1419044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895635

RESUMO

Glioblastoma multiforme (GBM) is one of the most prevalent and lethal primary central nervous system malignancies. GBM is notorious for its high rates of recurrence and therapy resistance and the PI3K/Akt pathway plays a pivotal role in its malignant behavior. Crebanine (CB), an alkaloid capable of penetrating the blood-brain barrier (BBB), has been shown to have inhibitory effects on proinflammatory molecules and multiple cancer cell lines via pathways such as PI3K/Akt. This study aims to investigate the efficacy and mechanisms of CB treatment on GBM. It is the first study to elucidate the anti-tumor role of CB in GBM, providing new possibilities for GBM therapy. Through a series of experiments, we demonstrate the significant anti-survival, anti-clonogenicity, and proapoptotic effects of CB treatment on GBM cell lines. Next-generation sequencing (NGS) is also conducted and provides a complete list of significant changes in gene expression after treatment, including genes related to apoptosis, the cell cycle, FoxO, and autophagy. The subsequent protein expressions of the upregulation of apoptosis and downregulation of PI3K/Akt are further proved. The clinical applicability of CB to GBM treatment could be high for its BBB-penetrating feature, significant induction of apoptosis, and blockage of the PI3K/Akt pathway. Future research is needed using in vivo experiments and other therapeutic pathways shown in NGS for further clinical or in vivo studies.

20.
Otol Neurotol ; 45(7): 759-764, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918073

RESUMO

OBJECTIVE: We used simple variables to construct prognostic prediction ensemble learning models for patients with sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospectively study. SETTING: Tertiary medical center. PATIENTS: 1,572 patients with SSNHL. INTERVENTION: Prognostic. MAIN OUTCOME MEASURES: We selected four variables, namely, age, days after onset of hearing loss, vertigo, and type of hearing loss. We also compared the accuracy between different ensemble learning models based on the boosting, bagging, AdaBoost, and stacking algorithms. RESULTS: We enrolled 1,572 patients with SSNHL; 73.5% of them showed improving and 26.5% did not. Significant between-group differences were noted in terms of age ( p = 0.011), days after onset of hearing loss ( p < 0.001), and concurrent vertigo ( p < 0.001), indicating that the patients who showed improving to treatment were younger and had fewer days after onset and fewer vertigo symptoms. Among ensemble learning models, the AdaBoost algorithm, compared with the other algorithms, achieved higher accuracy (82.89%), higher precision (86.66%), a higher F1 score (89.20), and a larger area under the receiver operating characteristics curve (0.79), as indicated by test results of a dataset with 10 independent runs. Furthermore, Gini scores indicated that age and days after onset are two key parameters of the predictive model. CONCLUSIONS: The AdaBoost model is an effective model for predicting SSNHL. The use of simple parameters can increase its practicality and applicability in remote medical care. Moreover, age may be a key factor influencing prognosis.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Perda Auditiva Neurossensorial/diagnóstico , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Perda Auditiva Súbita/diagnóstico , Estudos Retrospectivos , Adulto , Idoso , Inteligência Artificial , Algoritmos , Vertigem/diagnóstico , Adulto Jovem , Aprendizado de Máquina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA