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1.
Technol Health Care ; 32(1): 229-241, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37393449

RESUMEN

BACKGROUND: Stress urinary incontinence is prevalent among women and the incidence increases with age. OBJECTIVE: To explore the effect of intelligent pelvic floor muscle rehabilitation on elderly female patients with incontinence. METHODS: A total of 209 patients with urinary incontinence who were treated with pelvic floor muscle rehabilitation at Peking University International Hospital from September 2020 to January 2022 were selected by convenient sampling. All subjects were divided into the 50-60 year old patient group (n= 51) and over 60 years old patient group according to age (n= 158). The subjects of different age group were divided into an experimental group and a control group. The patients in the control group received routine nursing and health education, and the patients in the observation group received a combination of mobile application use and smart dumbbells. Based on this, we constructed an intervention model for intelligent, continuous pelvic floor rehabilitation. After 7 and 12 weeks, pelvic floor muscle function knowledge and exercise compliance in the two groups were evaluated. The improvement of urinary incontinence symptoms, pelvic floor muscle strength grades and quality-of-life scales were evaluated. RESULTS: The results showed that pelvic floor knowledge and exercise compliance in the experimental group were better than in the control group at 7 and 12 weeks after intervention (P< 0.05). There was no significant difference in pelvic floor muscle strength and quality of life between the two groups at 7 weeks after intervention (P> 0.05). However, there was a significant difference in pelvic floor muscle strength and quality of life between the two groups at 12 weeks after intervention (P< 0.05). There was no significant difference between different age groups. CONCLUSION: The intelligent pelvic floor rehabilitation model that combines a mobile application with smart dumbbells can maintain and strengthen the clinical treatment effect for elderly patients with urinary incontinence.


Asunto(s)
Teléfono Celular , Aplicaciones Móviles , Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Anciano , Femenino , Humanos , Persona de Mediana Edad , Terapia por Ejercicio/métodos , Diafragma Pélvico , Calidad de Vida , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/terapia
2.
Nano Lett ; 23(23): 11051-11056, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38088140

RESUMEN

Terahertz (THz) field enhancement has significant applications in high-resolution imaging, next-generation wireless communications, and networking. In this work, we experimentally demonstrate a graphene metasurface for THz field enhancement that is based on the intervalley scattering theory. Each meta-atom of the metasurface is composed of one split-ring resonator (SRR) embedded in one graphene patch. The experimental results show that, by electrically adjusting the conductivity of the graphene patch, the THz field through the entire sample is enhanced by 23 times and the transmission amplitude at 0.47 THz decreases 8.4 dB. Moreover, the maximum phase difference at 0.43 THz reaches 88°. The experiment shows good agreement with simulation. This study paves a way for exploring THz-matter interactions and nonlinear optics.

3.
Infect Dis Poverty ; 12(1): 114, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38062480

RESUMEN

BACKGROUND: Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are paid out of pocket and there is room to increase their coverage. We focused on four selected non-NIP vaccines in this study, namely Haemophilus influenzae type b (Hib) vaccine, human papillomavirus (HPV) vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine. We aimed to conduct a scoping review of their vaccination rates and the major barriers faced by health systems, providers, and caregivers to increase coverage. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). We searched five English databases (PubMed, Web of Science, EMBASE, Scopus, and WHO IRIS) and four Chinese databases using the search strategy developed by the study team. Two independent reviewers screened, selected studies, and examined their quality. We summarized the non-NIP vaccine coverage data by vaccine and applied the 5A framework (Access, Affordability, Acceptance, Awareness, Activation) to chart and analyze barriers to increasing coverage. RESULTS: A total of 28 articles were included in the analysis (nine pertaining to vaccine coverage, and another 19 reporting challenges of increasing uptake). Among the four selected vaccines, coverage for the Hib vaccine was the highest (54.9-55.9% for 1 dose or more from two meta-analyses) in 2016, while the coverage of the other three vaccines was lower than 30%. Eight of the nine included articles mentioned the regional disparity of coverage, which was lower in under-developing regions. For example, the three-dose Hib vaccination rate in eastern provinces was 38.1%, whereas the rate in central and western provinces was 34.3% and 26.2%, respectively in 2017. Within the 5A framework, acceptance, awareness, and affordability stood out as the most prominent themes. Among the 12 identified sub-themes, high prices, low vaccine awareness, concerns about vaccine safety and efficacy were the most cited barriers to increasing the uptake. CONCLUSIONS: There is an urgent need to increase coverage of non-NIP vaccines and reduce disparities in access to these vaccines across regions. Concerted efforts from the government, the public, and society are required to tackle the barriers and challenges identified in this study, both on the demand and supply side, to ensure everybody has equal access to life-saving vaccines in China. Particularly, the government should take a prudent approach to gradually incorporate non-NIP vaccines into the NIP step by step, and make a prioritizing strategy based on key factors such as disease burden, financial resources, and market readiness, with special attention to high-risk populations and underdeveloped regions.


Asunto(s)
Vacunas , Humanos , Vacunación , Programas de Inmunización , China , Costo de Enfermedad
4.
Appl Opt ; 62(33): 8905-8910, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38038036

RESUMEN

We propose a polarization insensitive, flexible ultra-broadband terahertz (THz) metamaterial absorber. It consists of a chromium composite resonator on the top, a polyimide (PI) dielectric layer in the middle, and a chromium substrate. The simulation results show that the absorption achieves more than 90% ultra-wideband absorption in the range of 1.92-4.34 THz. The broadband absorption is produced by the combination of electric dipole resonance and magnetic resonance, as well as impedance matching with free space. Due to the rotational symmetry of the unit structure, the absorber is insensitive to polarization of the THz wave and has a larger range of incident angles. The total thickness of the absorber is only 13.4 µm, showing highly flexible and excellent high-temperature resistance characteristics. Therefore, it has potential applications in THz wave stealth and electromagnetic shielding.

5.
Opt Lett ; 48(18): 4781-4784, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37707901

RESUMEN

Slow light devices have significant applications in memory, switching, and quantum optics. However, the design and fabrication of slow light devices with large tunable group delay are still challenging. Here, a graphene-based slow light device that can electrically modulate the group delay of terahertz (THz) waves is proposed and experimentally demonstrated. The unit cell of the device consists of a U-shaped metal resonator and an Ω-shaped metal resonator, with three graphene ribbons embedded between the two resonators. Under electrical stimuli, a relatively high amplitude modulation depth of 74% is achieved and the maximum transmission amplitude is as high as 0.7 at the transmission peak of 0.6 THz. Most importantly, the maximum group delay variation reaches 5 ps at 0.76 THz and the maximum group delay amplitude is as high as 8.8 ps. The experiment shows good agreement with simulation. This study paves a new way for developing novel switchable nanophotonic devices and slow light devices.

6.
Chin J Nat Med ; 21(6): 423-435, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37407173

RESUMEN

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.


Asunto(s)
Lesión Pulmonar Aguda , FN-kappa B , Humanos , FN-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Pulmón , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/farmacología , Proteínas de Unión a Fosfato/uso terapéutico , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Citotóxicas Formadoras de Poros/farmacología , Proteínas Citotóxicas Formadoras de Poros/uso terapéutico
7.
Biochim Biophys Acta Mol Basis Dis ; 1869(4): 166663, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36764621

RESUMEN

Fibrosis is a common pathological phenomenon in progressive kidney disease leading to eventual loss of kidney function. Previous studies demonstrated that CDC20 plays a role in cancers by regulating epithelial-mesenchymal transition (EMT) and the infiltration of fibroblasts, suggesting the potential of CDC20 in regulating fibrotic response. However, the role of CDC20 in renal fibrosis is yet unclear. Herein, we reported that renal CDC20 was remarkably upregulated in renal tubular epithelial cells and fibroblasts in chronic kidney disease (CKD) patients, which was in line with a positive correlation with the severity of kidney fibrosis. In mice with unilateral urinary obstruction, CDC20 was also strikingly enhanced, and treatment with Apcin, an inhibitor of CDC20, ameliorated kidney fibrosis. Consistently, the pharmacological inhibition of CDC20 in mouse proximal tubular epithelial cells and rat fibroblasts attenuated TGF-ß1-induced fibrotic responses, while overexpression of CDC20 aggravated such responses. Additional studies revealed that CDC20 induces nuclear translocation of ß-catenin, which in turn initiates and promotes the pathological process of fibrosis in CKD. Thus, enhanced CDC20 in renal tubular cells and fibroblasts promotes renal fibrosis by activating ß-catenin, and CDC20 inhibition may serve as a promising strategy for the prevention and treatment of renal fibrosis.


Asunto(s)
Insuficiencia Renal Crónica , beta Catenina , Animales , Ratones , Ratas , Proteínas Cdc20 , Proteínas de Ciclo Celular , Células Epiteliales/patología , Fibroblastos/patología , Fibrosis , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/patología , Humanos
8.
Appl Opt ; 62(4): 1103-1108, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36821170

RESUMEN

Actively controlling the phase of a terahertz (THz) wave is of great significance for beaming, tunable focusing, and holography. We present a THz phase modulator based on an electrically triggered vanadium dioxide (V O 2) reconfigurable metasurface. The unit cell of the device consists of two split-ring resonators embedded with a V O 2 ribbon. By electrically triggering the insulator-to-metal transition of V O 2, the resonance mode and resonance intensity of the unit cell can be dynamically controlled. The simulation results show that the structure can achieve a phase shift of about 360° in the range of 1.03-1.13 THz, and the reflection amplitude can reach 80%. The device has potential applications in THz imaging, radar, broadband wireless communications, and array phase control.

9.
EMBO Mol Med ; 15(2): e16581, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36629048

RESUMEN

Mitochondria comprise the central metabolic hub of cells and their imbalance plays a pathogenic role in chronic kidney disease (CKD). Here, we studied Lon protease 1 (LONP1), a major mitochondrial protease, as its role in CKD pathogenesis is unclear. LONP1 expression was decreased in human patients and mice with CKD, and tubular-specific Lonp1 overexpression mitigated renal injury and mitochondrial dysfunction in two different models of CKD, but these outcomes were aggravated by Lonp1 deletion. These results were confirmed in renal tubular epithelial cells in vitro. Mechanistically, LONP1 downregulation caused mitochondrial accumulation of the LONP1 substrate, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), which disrupted mitochondrial function and further accelerated CKD progression. Finally, computer-aided virtual screening was performed, which identified a novel LONP1 activator. Pharmacologically, the LONP1 activator attenuated renal fibrosis and mitochondrial dysfunction. Collectively, these results imply that LONP1 is a promising therapeutic target for treating CKD.


Asunto(s)
Proteasa La , Insuficiencia Renal Crónica , Animales , Humanos , Ratones , Proteasas ATP-Dependientes/metabolismo , Células Epiteliales/metabolismo , Hidroximetilglutaril-CoA Sintasa/metabolismo , Riñón/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteasa La/metabolismo , Insuficiencia Renal Crónica/metabolismo
10.
J Am Med Dir Assoc ; 24(5): 672-678, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36592938

RESUMEN

OBJECTIVES: This study aimed to investigate the effect of white matter hyperintensity (WMH), a common cerebral small vessel disease (CSVD) imaging marker, and age on gait parameters in middle-aged and geriatric populations. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1076 participants (62.9% female; age 61.0 ± 9.3 years), who visited the neurology clinic or obtained a physical check-up from the Affiliated Hospital of Guizhou Medical University. In total, 883 patients with WMH and 193 healthy controls were included in this study. METHODS: The Fazekas scores of patients with CSVD were used to assess the burden of WMH. Based on the Fazekas scores, all participants were divided into 4 groups: 553 patients with Fazekas I, 257 patients with Fazekas II, 73 patients with Fazekas III, and 193 controls. Gait parameters, including step speed, frequency, length, width, stance time, and swing time, were quantitatively assessed using a vision-based artificial intelligence gait analyzer (SAIL system). The relationships among the Fazekas scores, age, and gait parameters were analyzed. RESULTS: Step speed, step length, step width, stance time, and swing time were significantly different among the 4 groups. Furthermore, Fazekas scores and age were both associated with gait parameters, including step speed, step length, stance time, and swing time. The Fazekas scores were associated with step width, whereas age was not. Age was associated with step frequency, whereas Fazekas scores were not. CONCLUSIONS AND IMPLICATIONS: Fazekas score and age are useful for evaluating gait parameters in patients with CSVD. Emerging WMH (such as Fazekas Ⅰ) could be a clinical warning sign of gait disturbance in a geriatric population.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Sustancia Blanca , Persona de Mediana Edad , Humanos , Anciano , Femenino , Masculino , Sustancia Blanca/diagnóstico por imagen , Inteligencia Artificial , Estudios Transversales , Imagen por Resonancia Magnética , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Marcha
11.
Curr Neurovasc Res ; 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38509689

RESUMEN

BACKGROUND: Cerebral small vessel disease (CSVD) is a common chronic progressive disease. It remains unclear whether high gait variability is a marker of cognitive cortical dysfunction. METHODS: This study included 285 subjects (aged from 60 to 85 years, 60.3% female) including 37 controls, 179 presented as Fazekas II, and 69 presented as Fazekas III. The severity of white matter hyperintensities was assessed by the Fazekas Rating Scale. Gait parameters were assessed using a vision-based artificial intelligent gait analyzer. Cognitive function was tested by MMSE, MoCA, DST, and VFT. RESULTS: Three gait parameters including gait speed, gait length, and swing time were associated with cognitive performance in patients with CSVD. Gait speed was associated with cognitive performance, including MMSE (ß 0.200; 95%CI 1.706-6.018; P <.001), MoCA (ß 0.183; 95%CI 2.047-7.046; P <.001), DST (order) (ß 0.204; 95%CI 0.563-2.093; P =.001) and VFT (ß 0.162; 95%CI 0.753-4.865; P =.008). Gait length was associated with cognitive performance, including MMSE (ß 0.193; 95%CI 3.475-12.845; P =.001), MoCA (ß 0.213; 95%CI 6.098-16.942; P <.001), DST (order) (ß 0.224; 95%CI 1.056-4.839; P <.001) and VFT (ß 0.149; 95%CI 1.088- 10.114; P =.015). Swing time was associated with cognitive performance, including MMSE (ß - 0.242; 95%CI -2.639 to -0.974; P<.001), MoCA (ß -0.211; 95%CI -2.989 to -1.034; P <.001) and DST (reverse order) (ß -0.140; 95%CI -0.568 to -0.049; P =.020). CONCLUSION: This study revealed that the relationship between gait parameters and cognitive performance in patients with CSVD and the deteriorated gait parameters can reflect cognitive impairment and even dementia in older people with CSVD.

12.
Langmuir ; 38(12): 3739-3747, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35298154

RESUMEN

Owing to their stability in bodily fluids, exosomes have attracted increased attention as colorectal cancer (CRC) biomarkers for early diagnosis. To validate the potential of the plasma exosomes as a novel biomarker for the monitoring of CRC, we demonstrated a terahertz (THz) metamaterials (MMs) biosensor for the detection of exosomes in this work. The biosensor with two resonant frequencies is designed using full wave electromagnetic simulation software based on the finite integration time domain (FITD) method and fabricated by a surface micromachining process. The biosensor surface is first modified using Au nanoparticles (AuNPs), and then, anti-KRAS and anti-CD147, which are specific to the exosomes, are modified on the AuNPs assembled with HS-poly(ethylene glycol)-COOH (HS-PEG-COOH). Exosomes used in the experiment are extracted via the instructions in the exosomes isolation and purification kit and identified by using transmission electron microscopy (TEM), Western blot (WB), and nanoparticle tracking analysis (NTA). The biosensor covered with plasma-derived exosomes of CRC patients has a different resonance frequency shift compared to that with healthy-control-derived exosomes. This study proposes an emerging and quick method for diagnosing the CRC.


Asunto(s)
Técnicas Biosensibles , Exosomas , Nanopartículas del Metal , Biomarcadores , Técnicas Biosensibles/métodos , Oro , Humanos , Microscopía Electrónica de Transmisión
13.
Arch Public Health ; 79(1): 211, 2021 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-34823590

RESUMEN

BACKGROUND: Although Chinese government has dedicated the past decades to treating chronic diseases by primary healthcare system, many more residents are apt to choose higher-tier facilities to treat minor chronic diseases. Understanding residents' preferences for chronic disease management in primary care facilities can bridge the gap between residents' choices and policy implementation. This study aims to elicit residents' preferences for chronic disease management in primary care facilities in the hypothetical minor chronic disease scenario. METHODS: Six hundred eighty residents were administered a discrete choice experiment that elicited preferences for chronic disease management in primary care facilities. Services attributes were service mode, treatment measure, out-of-pocket expenditure (OOP), traveling time to healthcare facility and title of physician. Mixed logit models were used to estimate stated preferences and willingness to pay for attributes. WTP confidence intervals were estimated by the delta method. RESULTS: A total of 94.44% of the completed questionnaires were valid (680 of 720 respondents). The participants preferred chronic disease management service with modern medicine, traveling time ≤ 30mins, and less OOP expenditure. Compared with Traditional Chinese Medicine (TCM), residents prefer modern medicine, willing to pay 155.53 CNY ($21.97) to change from TCM to modern medicine. Compensation about 86.02 CNY ($12.15) was needed to enable residents to change the choice of the nearer primary care facility to a further one. Integrated medicine in community clinics by experts was residents' most preferred scenario while TCM in the tertiary hospital was their least preferred one. CONCLUSION: In order to increase the utilization of primary healthcare services in chronic diseases management, policy makers need to concern more about the services of medical treatment type, price and convenience. Therefore, we advise policy makers to provide nearer primary healthcare services for residents especially for residents in surrounding areas. Furthermore, balancing the resource allocation between Traditional Chinese Medicine and modern medicine is worthy of consideration.

14.
Kidney Dis (Basel) ; 7(4): 293-305, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34395544

RESUMEN

BACKGROUND: Podocyte injury contributes to progressive glomerulosclerosis. Previously, we demonstrated the important role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mediating the podocyte injury induced by aldosterone. Silent mating type information regulation 2 homolog 1 (SIRT1) is an NAD+-dependent deacetylase that is associated with the regulation of cellular inflammation. However, whether the activation of the NLRP3 inflammasome in podocytes is regulated by SIRT1, and the mechanism involved, remains unknown. METHODS: In this study, we detected SIRT1 expression in patients with podocyte disease and performed an aldosterone infusion model in podocyte-specific Sirt1 knockout mice. In cultured podocytes, we used plasmids to overexpress SIRT1 and treated the podocyte with aldosterone. RESULTS: SIRT1 was significantly decreased in the glomeruli of patients with podocyte disease. Sirt1-deficient mice showed significant urinary albumin excretion after aldosterone infusion, and the severity of the glomerular injury was significantly greater in podocyte-specific Sirt1 knockout mice than in the wild-type mice. Moreover, podocyte conditional Sirt1 knockout aggravated NLRP3 inflammasome activation and mitochondrial dysfunction (MtD). In vitro, overexpression of SIRT1 inhibited NLRP3 activation, protected against MtD and podocyte injury. CONCLUSION: Taken together, these findings revealed a novel regulatory mechanism of the NLRP3 inflammasome by SIRT1 by promoting mitochondrial function, which provides some potential targets for the treatment of glomerular diseases.

15.
Tissue Cell ; 73: 101622, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34454367

RESUMEN

In this study, a three-dimensional (3D) thermo-reversible gelation polymer (TGP) culture system was established for organoid culture of mouse fallopian tube (FT) epithelial stem cells (FTESCs) without cell isolation. FT tissues from 6- to 8-week-old ICR mice were digested with collagenase, and whole FT cells (FTCs) were inoculated into the TGP. After 6 days of culture, many spheres in the TGP formed. Some cells in the spheres were positive for 5-ethynyl-2'-deoxyuridine (EdU), a marker of cell proliferation. Furthermore, all the spheres that formed in the TGP were also labelled for EpCAM and LGR5. Some cells in the spheres were stained for PAX8, a secretory cell marker, and fewer cells were labelled with TUBB4, a ciliated cell marker. These results indicate that the 3D TGP culture system is a useful tool for organoid culture of FTESCs in vitro.


Asunto(s)
Técnicas de Cultivo de Célula , Células Epiteliales/citología , Trompas Uterinas/citología , Geles/química , Organoides/citología , Polímeros/farmacología , Células Madre/citología , Temperatura , Animales , Biomarcadores/metabolismo , Cilios/metabolismo , Molécula de Adhesión Celular Epitelial/metabolismo , Femenino , Ratones Endogámicos ICR , Factor de Transcripción PAX8/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Esferoides Celulares/citología , Tubulina (Proteína)/metabolismo
16.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166227, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34311081

RESUMEN

Renal fibrosis, a common feature of chronic kidney disease (CKD), is characterized by excessive deposition of extracellular matrix (ECM) leading to scar formation in the renal parenchyma. Active epithelial-mesenchymal communication (EMC), and the proliferation and activation of fibroblasts are implicated in the causation of renal fibrosis. Aurora-A kinase (AURKA) is a serine/threonine kinase required for the process of mitosis. Dysregulation of AURKA has been demonstrated in the context of various cancers. However, the role of AURKA in CKD-associated fibrosis has not been elucidated. MK-5108, a potent and highly selective AURKA inhibitor, was shown to exhibit anti-cancer activity in recent preclinical and clinical studies. In the present study, we investigated the role of MK-5108 in renal fibrosis employing animal and cell models. In vivo, AURKA was highly expressed in fibrotic kidneys of CKD patients and in mouse kidneys with unilateral ureteral obstruction (UUO). Post treatment with MK-5108 at the 3rd day after UUO remarkably alleviated renal fibrosis, possibly by inhibiting the proliferation and activation of fibroblasts and suppressing the phenotypic transition of renal cells. Moreover, the enhanced inflammatory factors in obstructive kidneys were also repressed. In vitro, MK-5108 treatment inhibited the pro-fibrotic response in renal cells induced by transforming growth factor-ß1. Finally, overexpression of AURKA in renal fibroblasts promoted fibrotic response, while silencing AURKA showed anti-fibrotic effect, further confirming the pro-fibrotic role of AURKA. In this study, inhibition of AURKA by MK-5108 markedly attenuated renal fibrosis. MK-5108 is a potential therapeutic agent for treatment of renal fibrosis in CKD.


Asunto(s)
Aurora Quinasa A/antagonistas & inhibidores , Ácidos Ciclohexanocarboxílicos/farmacología , Riñón/patología , Insuficiencia Renal Crónica/tratamiento farmacológico , Tiazoles/farmacología , Animales , Aurora Quinasa A/metabolismo , Biopsia , Línea Celular , Niño , Preescolar , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Fibrosis , Humanos , Lactante , Riñón/efectos de los fármacos , Masculino , Ratones , Ratas , Insuficiencia Renal Crónica/patología , Tiazoles/uso terapéutico
17.
Chemistry ; 27(35): 9060-9070, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-33847398

RESUMEN

The interaction between Cu and Mn has been used to immobilize the Cu single-atom on MnO2 surface by redox-driven hydrolysis. Comprehensive structure and property characterizations demonstrate that the existence of an Cu-Mn interaction on the catalyst surface can effectively restrain the aggregation of Cu single atoms and improve carbon monoxide (CO) oxidation activity. The interaction of forming the Cu-O-Mn entity is beneficial for CO catalytic activity as the migration of reactive oxygen species and the coordination effect of active centers accelerate the reaction. In particular, 3%-Cu1 /MnO2 shows an oxygen storage capacity (OSC) value (342.75 µmol/g) more than ten times that of pure MnO2 (27.79 µmol/g) and has high CO catalytic activity (T90% =80 °C), it can maintain CO conversion of 95 % after 15 cycles. This work offers a reliable method for synthesizing Cu single-atom catalysts and deepens understanding of the interaction effect between single transition metal atoms and supports that can improve the catalytic activity of CO oxidation.

18.
Am J Physiol Cell Physiol ; 320(3): C264-C269, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33296285

RESUMEN

Cell proliferation and differentiation are the foundation of reproduction and growth. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases, or cell death. Myeloid ecotropic viral integration site 1 (MEIS1) was initially discovered in leukemic mice. Recent research identified MEIS1 as an important transcription factor that regulates cell proliferation and differentiation during cell fate commitment. MEIS1 has a pro-proliferative effect in leukemia cells; however, its overexpression in cardiomyocytes restrains neonatal and adult cardiomyocyte proliferation. In addition, MEIS1 has carcinogenic or tumor suppressive effects in different neoplasms. Thus, this uncertainty suggests that MEIS1 has a unique function in cell proliferation and differentiation. In this review, we summarize the primary findings of MEIS1 in regulating cell proliferation and differentiation. Correlations between MEIS1 and cell fate specification might suggest MEIS1 as a therapeutic target for diseases.


Asunto(s)
Diferenciación Celular/genética , Proliferación Celular/genética , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide/genética , Animales , Carcinogénesis/genética , Humanos , Miocitos Cardíacos/patología
19.
Artículo en Inglés | MEDLINE | ID: mdl-33203010

RESUMEN

OBJECTIVES: This study aims to elicit the relative importance of treatment attributes that influence residents' choice, assuming they are suffering severe non-communicable diseases (NCDs), to explore how they make trade-offs between these attributes and to estimate the monetary value placed on different attributes and attribute levels. METHODS: A discrete choice experiment (DCE) was conducted with adults over 18 years old in China. Preferences were evaluated based on four treatment attributes: care provider, mode of service, distance to practice and cost. A mixed logit model was used to analyze the relative importance of the four attributes and to calculate the willingness to pay (WTP) for a changed attribute level. RESULTS: A total of 93.47% (2019 of 2160) respondents completed valid questionnaires. The WTP results suggested that participants would be willing to pay CNY 822.51 (USD 124.86), CNY 470.54 (USD 71.41) and CNY 68.20 (USD 10.35) for services provided by experts, with integrated traditional Chinese medicine (TCM) and Western medicine (WM) and with a service distance <=30 min, respectively. CONCLUSIONS: The results suggested that mode of service, care provider, distance to practice and cost should be considered in priority-setting decisions. The government should strengthen the curative service capability in primary health facilities and give full play to the role of TCM in the prevention and treatment of severe chronic diseases.


Asunto(s)
Servicios de Salud , Enfermedades no Transmisibles , Prioridad del Paciente , Adulto , China , Conducta de Elección , Enfermedad Crónica , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Enfermedades no Transmisibles/economía , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/terapia , Prioridad del Paciente/economía , Prioridad del Paciente/estadística & datos numéricos , Encuestas y Cuestionarios
20.
Am J Physiol Renal Physiol ; 319(6): F1105-F1116, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33073587

RESUMEN

Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.


Asunto(s)
Lesión Renal Aguda/metabolismo , Metabolismo Energético , Riñón/metabolismo , Mitocondrias/metabolismo , Dinámicas Mitocondriales , Mitofagia , Insuficiencia Renal Crónica/metabolismo , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/patología , Animales , Progresión de la Enfermedad , Humanos , Riñón/patología , Mitocondrias/patología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/patología , Factores de Riesgo
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