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1.
J Neuroeng Rehabil ; 21(1): 116, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997727

RESUMO

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.


Assuntos
Frequência Cardíaca , Caminhada , Humanos , Idoso , Masculino , Feminino , Caminhada/fisiologia , Frequência Cardíaca/fisiologia , Teste de Esforço , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Desempenho Psicomotor/fisiologia , Perna (Membro)/fisiologia
3.
Insights Imaging ; 15(1): 177, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39020237

RESUMO

OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.

4.
Nat Hum Behav ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886532

RESUMO

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.

5.
Front Endocrinol (Lausanne) ; 15: 1280692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38894748

RESUMO

Background: The prevalence of obesity among women of reproductive age is increasing worldwide, with implications for serious pregnancy complications. Methods: Following PRISMA guidelines, a systematic search was conducted in both Chinese and English databases up to December 30, 2020. Pregnancy complications and outcomes including gestational diabetes mellitus (GDM), gestational hypertension (GHTN), pre-eclampsia, cesarean section (CS), induction of labor (IOL), and postpartum hemorrhage (PPH) were analyzed. Random-effects or fixed-effects models were utilized to calculate the odds ratio (OR) with 95% confidence intervals (CIs). Results: Women with overweight and obesity issues exhibited significantly higher risks of GDM (OR, 2.92, 95%CI, 2.18-2.40 and 3.46, 95%CI, 3.05-3.94, respectively) and GHTN (OR, 2.08, 95%CI, 1.72-2.53 and 3.36, 95%CI, 2.81-4.00, respectively) compared to women of normal weight. Pre-eclampsia was also significantly higher in women with overweight or obesity, with ORs of 1.70 (95%CI, 1.44-2.01) and 2.82 (95%CI, 2.66-3.00), respectively. Additionally, mothers with overweight or obesity issues had significantly higher risks of CS (OR, 1.44, 95%CI, 1.41-1.47, and 2.23, 95%CI, 2.08-2.40), IOL (OR, 1.33, 95%CI, 1.30-1.35 and 1.96, 95%CI, 1.85-2.07), and PPH (OR, 1.67, 95%CI, 1.42-1.96 and 1.88, 95%CI, 1.55-2.29). Conclusion: Women with overweight or obesity issues face increased risks of pregnancy complications and adverse outcomes, indicating dose-dependent effects.


Assuntos
Índice de Massa Corporal , Complicações na Gravidez , Resultado da Gravidez , Humanos , Gravidez , Feminino , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Diabetes Gestacional/epidemiologia , Pré-Eclâmpsia/epidemiologia , Cesárea/estatística & dados numéricos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia
6.
Geroscience ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910193

RESUMO

Virtual error amplification (VEA) in visual feedback enhances attentive control over postural stability, although the neural mechanisms are still debated. This study investigated the distinct cortical control of unsteady stance in older adults using VEA through cross-frequency modulation of postural fluctuations and scalp EEG. Thirty-seven community-dwelling older adults (68.1 ± 3.6 years) maintained an upright stance on a stabilometer while receiving either VEA or real error feedback. Along with postural fluctuation dynamics, phase-amplitude coupling (PAC) and amplitude-amplitude coupling (AAC) were analyzed for postural fluctuations under 2 Hz and EEG sub-bands (theta, alpha, and beta). The results revealed a higher mean frequency of the postural fluctuation phase (p = .005) and a greater root mean square of the postural fluctuation amplitude (p = .003) with VEA compared to the control condition. VEA also reduced PAC between the postural fluctuation phase and beta-band EEG in the left frontal (p = .009), sensorimotor (p = .002), and occipital (p = .018) areas. Conversely, VEA increased the AAC of posture fluctuation amplitude and beta-band EEG in FP2 (p = .027). Neither theta nor alpha band PAC or AAC were affected by VEA. VEA optimizes postural strategies in older adults during stabilometer stance by enhancing visuospatial attentive control of postural responses and facilitating the transition of motor states against postural perturbations through a disinhibitory process. Incorporating VEA into virtual reality technology is advocated as a valuable strategy for optimizing therapeutic interventions in postural therapy, particularly to mitigate the risk of falls among older adults.

7.
Mol Cancer Ther ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907533

RESUMO

M2-like macrophages exhibit immunosuppressive activity and promote pancreatic cancer progression. Reactive oxygen species (ROS) affect macrophage polarization; however, the mechanism remains unclear. This study aimed to elucidate the underlying molecular basis and design a gene therapy to inhibit M2-like polarization. Microarray analysis and IF staining were performed in M1-like and M2-like macrophages to ascertain the expression of CYBB, a major intracellular ROS source. Co-culture assay and syngeneic orthotopic pancreatic cancer mouse models were used to study the mechanism of M2-like skewing. Decoy oligodeoxynucleotides (ODNs) were designed to manipulate CYBB transcription to inhibit M2-like polarization and control tumor growth. Lipopolysaccharide (LPS) treatment polarized U937 cells to M1-like macrophages in which CYBB expression was increased. In contrast, co-culture with PANC-1 cells induced M2-like polarization in U937 cells with CYBB downregulation. High CD204 M2-like expression in combination with low CYBB expression was associated with the worst prognosis in pancreatic cancer patients. STAT6 and HDAC2 in U937 cells were activated by cancer cell-derived IL-4 after coculture and then bound to the CYBB promoter to repress CYBB expression, resulting in M2-like polarization. DPI that inhibits ROS production could block this action. Knockdown of STAT6 and HDAC2 also inhibited M2-like polarization and maintained the M1-like phenotype of U937 cells after coculture. Decoy ODNs interrupting the binding of STAT6 to the CYBB promoter counteracted M2-like polarization and tumor growth and triggered antitumor immunity in vivo. Gene therapy using STAT6-CYBB decoy ODNs can inhibit M2-like polarization, representing a potential therapeutic tool for pancreatic cancer.

8.
J Ethnopharmacol ; 333: 118484, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38925318

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Meibomian gland dysfunction (MGD), complicated by type 2 diabetes, is associated with a high incidence of ocular surface disease, and no effective drug treatment exists. Diabetes mellitus (DM) MGD shows a notable disturbance in lipid metabolism. Er-Dong-Xiao-Ke decoction (EDXKD) has important functions in nourishing yin, clearing heat, and removing blood stasis, which are effective in the treatment of DM MGD. AIM OF THE STUDY: To observe the therapeutic effect of EDXKD on DM MGD and its underlying molecular mechanism. MATERIALS AND METHODS: After establishing a type 2 DM (T2DM)-induced MGD rat model, different doses of EDXKD and T0070907 were administered. The chemical constituents of EDXKD were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the molecular mechanism of EDXKD in treating DM MGD was predicted using network pharmacology. Lipid metabolism in DM meibomian glands (MGs) was analyzed using LC-MS/MS, and lipid biomarkers were screened and identified. Histological changes and lipid accumulation in MGs were detected by staining, and Peroxisome proliferator-activated receptor gamma (PPARG) expression in MG acinar cells was detected by immunofluorescence. The expression of lipid metabolism-related factors was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or western blotting. RESULTS: EDXKD reduced lipid accumulation in the MGs and improved the ocular surface index in DM MGD rats. The main active components of EDXKD had advantages in lipid regulation. Additionally, the PPARG signaling pathway was the key pathway of EDXKD in the treatment of DM MGD. Twelve lipid metabolites were biomarkers of EDXKD in the treatment of DM MGD, and glycerophospholipid metabolism was the main pathway of lipid regulation. Moreover, EDXKD improved lipid deposition in the acini and upregulated the expression of PPARG. Further, EDXKD regulated the PPARG-mediated UCP2/AMPK signaling network, inhibited lipid production, and promoted lipid transport. CONCLUSION: EDXKD is an effective treatment for MGD in patients with T2DM. EDXKD can regulate lipids by regulating the PPARG-mediated UCP2/AMPK signaling network, as it reduced lipid accumulation in the MGs of DM MGD rats, promoted lipid metabolism, and improved MG function and ocular surface indices.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Metabolismo dos Lipídeos , Disfunção da Glândula Tarsal , PPAR gama , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR gama/metabolismo , Masculino , Ratos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Transdução de Sinais/efeitos dos fármacos , Disfunção da Glândula Tarsal/tratamento farmacológico , Disfunção da Glândula Tarsal/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Glândulas Tarsais/efeitos dos fármacos , Glândulas Tarsais/metabolismo
9.
J Dent ; 147: 105109, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38849053

RESUMO

OBJECTIVES: The present study aimed to evaluate the effectiveness of bioactive glass (BAG) in preventing dental erosion in primary teeth. METHODS: Enamel and dentin specimens (2 × 2 × 2 mm) were obtained from extracted primary teeth, which were randomly divided into the following groups based on the pretreatments (n = 12): DW (deionized water), NaF (2 % sodium fluoride), 2BAG (2 % BAG), 4BAG (4 % BAG), 6BAG (6 % BAG), and 8BAG (8 % BAG). The specimens were immersed in the respective solutions for 2 min and subjected to in vitro erosive challenges (4 × 5 min/d) for 5 d. The erosive enamel loss (EEL), erosive dentin loss (EDL), and the thickness of the demineralized organic matrix (DOM) were measured using a contact profilometer. The surface microhardness (SMH) was measured, and the percentage of SMH loss (%SMHL) was calculated. The surface morphology and mineral composition were evaluated by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. RESULTS: After the erosive challenges, the EEL, EDL, and%SMHL of the 2BAG, 4BAG, 6BAG, and 8BAG groups significantly reduced, with the greatest reduction was observed in the 6BAG (EEL: 6.5 ± 0.2 µm;%SMHL in enamel: 12.8 ± 2.6; EDL: 7.9 ± 0.3 µm; %SMHL in dentin: 22.1 ± 2.7) and 8BAG groups (EEL: 6.4 ± 0.4 µm;%SMHL in enamel: 11.0 ± 1.9; EDL: 7.8 ± 0.5 µm; %SMHL in dentin: 22.0 ± 2.5) (P < 0.05). With increasing BAG concentrations, the number of surface deposits containing Ca, P, and Si increased. CONCLUSIONS: 6BAG was the most effective for preventing dental erosion in primary teeth and showed a particularly strong potential for dentin erosion prevention. CLINICAL SIGNIFICANCE: Bioactive glass, especially at a 6 % concentration, has proven effective in reducing erosive tooth wear and surface microhardness loss while also protecting demineralized organic matrix in primary dentin.


Assuntos
Esmalte Dentário , Dentina , Vidro , Dureza , Microscopia Eletrônica de Varredura , Fluoreto de Sódio , Espectrometria por Raios X , Erosão Dentária , Dente Decíduo , Erosão Dentária/prevenção & controle , Humanos , Vidro/química , Fluoreto de Sódio/uso terapêutico , Propriedades de Superfície , Cerâmica/química , Desmineralização do Dente/prevenção & controle , Teste de Materiais
10.
Am J Epidemiol ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825331

RESUMO

The aim of the present study was to investigate if use of antidepressants is related to the risk of developing lower (WHO grade 2-3) and higher grade (WHO grade 4) glioma. A registry-based case-control study was performed using 1283 glioma cases and 6400 age-, sex- and geographically matched controls, diagnosed in Sweden 2009-2013. Conditional logistic regression was used to analyze whether Selective Serotonin Reuptake Inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the dataset from the present study was combined with results from two previous epidemiological studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (OR 0.90 [95% CI 0.83-0.97]), when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma.

11.
Prosthet Orthot Int ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38896541

RESUMO

BACKGROUND: Stretching exercise is generally used for improving flexibility. However, its application to promote orthotic treatment for patients with adolescent idiopathic scoliosis (AIS) remains unknown. OBJECTIVE: This study was to explore the effect of pre-orthosis stretching exercises on spinal flexibility and initial in-orthosis correction for the patients with AIS. STUDY DESIGN: A pilot-controlled study. METHODS: An experimental group (EG) of 13 subjects (10 girls and 3 boys) with AIS allocating to self-stretching exercises and a control group (CG) of 19 AIS subjects (14 girls and 5 boys) with no stretching before orthosis fitting were recruited. The spinal flexibility of the EG was evaluated with an ultrasound imaging system and physical measurements. The initial in-orthosis correction rates between the 2 groups were compared with the independent t test, and the correlation analysis between the spinal flexibility measured from ultrasound images and physical measurement was performed with the Pearson correlation test. RESULTS: The initial Cobb angle of EG and CG were 25.70° ± 7.30° and 28.09° ± 5.58°, respectively. No significant difference was observed between the initial in-orthosis Cobb angle of EG (11.13° ± 6.80°) and CG (15.65° ± 9.10°) (p = 0.06). However, the spinal flexibility after stretching exercises was improved (p < 0.001), and the spinal flexibility changes measured with ultrasound and physical forward-bending method were significantly correlated (r = 0.57, p < 0.05). CONCLUSION: Stretching exercises before orthotic treatment could improve the spinal flexibility but did not cause a better in-orthosis correction. A study with a larger sample size and longer follow-up period should be conducted to investigate the long-term effect of stretching exercises.

12.
Kaohsiung J Med Sci ; 40(7): 660-670, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38801488

RESUMO

Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)-21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR-21, prognostic value of miR-21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR-21, miR-4454, and urine cytology for Ta-T1 and T2-T4 stage BC were analyzed. Urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 were highly expressed in BC patients. miR-146a-5p, miR-93-5p, miR-663b, miR-21, miR-4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR-21, miR-4454, and miRNA co-diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR-21 was closely related to Tumor-Node-Metastasis staging and grading in BC patients. Urinary exosomal miR-21 had high diagnostic value for BC and Ta-T1 and T2-T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.


Assuntos
Exossomos , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , MicroRNAs/urina , MicroRNAs/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Feminino , Exossomos/genética , Exossomos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Idoso , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Estudos de Casos e Controles , Estadiamento de Neoplasias
13.
Adv Sci (Weinh) ; 11(26): e2402759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704681

RESUMO

Soft on-skin electrodes play an important role in wearable technologies, requiring attributes such as wearing comfort, high conductivity, and gas permeability. However, conventional fabrication methods often compromise simplicity, cost-effectiveness, or mechanical resilience. In this study, a mechanically robust and gas-permeable on-skin electrode is presented that incorporates Flash Graphene (FG) integrated with a bioinspired armor design. FG, synthesized through Flash Joule Heating process, offers a small-sized and turbostratic arrangement that is ideal for the assembly of a conductive network with nanopore structures. Screen-printing is used to embed the FG assembly into the framework of polypropylene melt-blown nonwoven fabrics (PPMF), forming a soft on-skin electrode with low sheet resistance (125.2 ± 4.7 Ω/□) and high gas permeability (≈10.08 mg cm⁻2 h⁻¹). The "armor" framework ensures enduring mechanical stability through adhesion, washability, and 10,000 cycles of mechanical contact friction tests. Demonstrating capabilities in electrocardiogram (ECG) and electromyogram (EMG) monitoring, along with serving as a self-powered triboelectric sensor, the FG/PPMF electrode holds promise for scalable, high-performance flexible sensing applications, thereby enriching the landscape of integrated wearable technologies.


Assuntos
Eletrodos , Grafite , Dispositivos Eletrônicos Vestíveis , Grafite/química , Humanos , Desenho de Equipamento/métodos , Permeabilidade , Nanoporos , Eletrocardiografia/métodos , Gases
14.
Virus Res ; 345: 199391, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754785

RESUMO

Coronaviruses (CoVs) are enveloped single-stranded RNA viruses that predominantly attack the human respiratory system. In recent decades, several deadly human CoVs, including SARS-CoV, SARS-CoV-2, and MERS-CoV, have brought great impact on public health and economics. However, their high infectivity and the demand for high biosafety level facilities restrict the pathogenesis research of CoV infection. Exacerbated inflammatory cell infiltration is associated with poor prognosis in CoV-associated diseases. In this study, we used human CoV 229E (HCoV-229E), a CoV associated with relatively fewer biohazards, to investigate the pathogenesis of CoV infection and the regulation of neutrophil functions by CoV-infected lung cells. Induced pluripotent stem cell (iPSC)-derived alveolar epithelial type II cells (iAECIIs) exhibiting specific biomarkers and phenotypes were employed as an experimental model for CoV infection. After infection, the detection of dsRNA, S, and N proteins validated the infection of iAECIIs with HCoV-229E. The culture medium conditioned by the infected iAECIIs promoted the migration of neutrophils as well as their adhesion to the infected iAECIIs. Cytokine array revealed the elevated secretion of cytokines associated with chemotaxis and adhesion into the conditioned media from the infected iAECIIs. The importance of IL-8 secretion and ICAM-1 expression for neutrophil migration and adhesion, respectively, was demonstrated by using neutralizing antibodies. Moreover, next-generation sequencing analysis of the transcriptome revealed the upregulation of genes associated with cytokine signaling. To summarize, we established an in vitro model of CoV infection that can be applied for the study of the immune system perturbations during severe coronaviral disease.


Assuntos
Células Epiteliais Alveolares , Células-Tronco Pluripotentes Induzidas , Neutrófilos , Humanos , Neutrófilos/imunologia , Neutrófilos/virologia , Células-Tronco Pluripotentes Induzidas/virologia , Células Epiteliais Alveolares/virologia , COVID-19/virologia , COVID-19/imunologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , SARS-CoV-2/imunologia , Interleucina-8/genética , Interleucina-8/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-38780269

RESUMO

As obesity has raised heightening awareness, researchers have attempted to identify potential targets that can be treated for therapeutic intervention. Focusing on the central nervous system (CNS), the key organ in maintaining energy balance, a plethora of ion channels that are expressed in the CNS have been inspected and determined through manipulation in different hypothalamic neural subpopulations for their roles in fine-tuning neuronal activity on energy state alterations, possibly acting as metabolic sensors. However, a remaining gap persists between human clinical investigations and mouse studies. Despite having delineated the pathways and mechanisms of how the mouse study-identified ion channels modulate energy homeostasis, only a few targets overlap with the obesity-related risk genes extracted from human genome-wide association studies. Here, we present the most recently discovered CNS-specific metabolism-correlated ion channels using reverse and forward genetics approaches in mice and humans, respectively, in the hope of illuminating the prospects for future therapeutic development.


Assuntos
Canalopatias , Obesidade , Humanos , Animais , Obesidade/genética , Obesidade/metabolismo , Canalopatias/genética , Canalopatias/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Metabolismo Energético/genética , Camundongos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia
16.
Bioorg Chem ; 148: 107495, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38805850

RESUMO

Targeting Ribonuclease H (RNase H) has been considered a viable strategy for HIV therapy. In this study, a series of novel thiazolo[3, 2-a]pyrimidine derivatives were firstly designed and synthesized as potential inhibitors of HIV-1 RNase H. Among these compounds, A28 exhibited the most potent inhibition against HIV-1 RNase H with an IC50 value of 4.14 µM, which was about 5-fold increase in potency than the hit compound A1 (IC50 = 21.49 µM). To gain deeper insights into the structure-activity relationship (SAR), a CoMFA model was constructed to yield reasonable statistical results (q2 = 0.658 and R2 = 0.969). Results from magnesium ion chelation experiments and molecular docking studies revealed that these thiazolopyrimidine inhibitors may exert their inhibitory activity by binding to an allosteric site on RNase H at the interface between subunits p51 and p66. Furthermore, this analog demonstrated favorable physicochemical properties. Our findings provide valuable groundwork for further development of allosteric inhibitors targeting HIV-1 RNase H.


Assuntos
Desenho de Fármacos , HIV-1 , Simulação de Acoplamento Molecular , Pirimidinas , Relação Estrutura-Atividade , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Humanos , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Estrutura Molecular , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Ribonuclease H/antagonistas & inibidores , Ribonuclease H/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Ribonuclease H do Vírus da Imunodeficiência Humana/antagonistas & inibidores , Ribonuclease H do Vírus da Imunodeficiência Humana/metabolismo
17.
ACS Nano ; 18(22): 14496-14506, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38771969

RESUMO

Hydrogen obtained from electrochemical water splitting is the most promising clean energy carrier, which is hindered by the sluggish kinetics of the oxygen evolution reaction (OER). Thus, the development of an efficient OER electrocatalyst using nonprecious 3d transition elements is desirable. Multielement synergistic effect and lattice oxygen oxidation are two well-known mechanisms to enhance the OER activity of catalysts. The latter is generally related to the high valence state of 3d transition elements leading to structural destabilization under the OER condition. We have found that Al doping in nanosheet Ni-Fe hydroxide exhibits 2-fold advantage: (1) a strong enhanced OER activity from 277 mV to 238 mV at 10 mA cm-2 as the Ni valence state increases from Ni3.58+ to Ni3.79+ observed from in situ X-ray absorption spectra. (2) Operational stability is strengthened, while weakness is expected since the increased NiIV content with 3d8L2 (L denotes O 2p hole) would lead to structural instability. This contradiction is attributed to a reduced lattice oxygen contribution to the OER upon Al doping, as verified through in situ Raman spectroscopy, while the enhanced OER activity is interpreted as an enormous gain in exchange energy of FeIV-NiIV, facilitated by their intersite hopping. This study reveals a mechanism of Fe-Ni synergy effect to enhance OER activity and simultaneously to strengthen operational stability by suppressing the contribution of lattice oxygen.

19.
Ultrason Sonochem ; 106: 106883, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703594

RESUMO

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.


Assuntos
Antioxidantes , Fenômenos Químicos , Ficus , Pectinas , Ondas Ultrassônicas , Pectinas/química , Pectinas/isolamento & purificação , Ficus/química , Antioxidantes/química , Temperatura , Tamanho da Partícula , Concentração de Íons de Hidrogênio
20.
Sci Total Environ ; 930: 172732, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38663609

RESUMO

East Asian continental outflows with PM2.5, O3, and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM2.5, O3, CO2, and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O3 concentrations (70-100 ppbv) but relatively low concentrations of PM2.5 (10-20 µg/m3), CO2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM2.5, CO2, and VOCs ruled out photochemistry as the cause of the formation of high-level O3. Further coordination of spatiotemporal data with air mass trajectories and O3 cross sections provided by MERRA-2 suggested that the high O3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O3 may be involved in the rising trend in O3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors.

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