RESUMO
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly worldwide. Multiple studies have shown that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of AMD. Isorhamnetin (Isor) is a flavonoid compound that inhibits EMT in tumor cells. However, whether it can also attenuate EMT in the retinal pigment epithelium (RPE) is unknown. Therefore, our study was designed to probe the possible impact of Isor on EMT process in both mouse retina and ARPE-19 cells. C57BL/6 mice were utilized to establish a dry AMD model. Isor and LCZ (a mixture of luteine/ß-carotene/zinc gluconate) were administered orally for 3 months. The effects of Isor on the retina were evaluated using fundus autofluorescence, optical coherence tomography, and transmission electron microscopy. Transwell and wound healing assay were employed to assess ARPE-19 cell migration. Western blotting and immunofluorescence were used to measure the protein expressions associated with EMT, Nrf2 and AKT/GSK-3ß pathway. The findings indicated that Isor alleviated dry AMD-like pathological changes in vehicle mice retina, inhibited the migration of Ox-LDL-treated ARPE-19 cells, and repressed the EMT processes in vivo and in vitro. Furthermore, Isor activated Nrf2 pathway and deactivated AKT/GSK-3ß pathway in both vehicle mice and ARPE-19 cells. Interestingly, when Nrf2 siRNA was transfected into ARPE-19 cells, the inhibitory effect of Isor on EMT and AKT/GSK-3ß pathway was attenuated. These results suggested that Isor inhibited EMT processes via Nrf2-dependent AKT/GSK-3ß pathway and is a promising candidate for dry AMD treatment.
Assuntos
Proteínas Proto-Oncogênicas c-akt , Quercetina/análogos & derivados , Transdução de Sinais , Humanos , Camundongos , Animais , Idoso , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Transição Epitelial-MesenquimalRESUMO
Choroidal neovascularization (CNV) is a hallmark of wet age-related macular degeneration, which severely impairs central vision. Studies have shown that endothelial-mesenchymal transition (EndMT) is involved in the pathogenesis of CNV. Licochalcone A (lico A), a flavonoid extracted from the root of licorice, shows the inhibition on EndMT, but it remains unclear whether it can suppress the formation of CNV. The aim of this study is to investigate the effects of lico A on laser-induced CNV, and EndMT process in vitro and vivo. We established the model of CNV with a krypton laser in Brown-Norway rats and then intraperitoneally injected lico A. Our experimental results demonstrated that the leakage of CNV was relieved, and the area of CNV was reduced in lico A-treated rats. Cell migration and tube formation in oxidized low-density lipoprotein (Ox-LDL)-stimulated HUVECs were inhibited by lico A and promoted by PI3K activator 740Y-P. The protein expressions of snai1 and α-SMA were increased, and CD31 and VE-cadherin were decreased in the model rats of CNV, but partially reversed after treatment with lico A. The expression of CD31 was decreased and α-SMA was increased in OX-LDL-treated HUVECs, which was further strengthened by 740Y-P, while the expression of CD31 was up-regulated and α-SMA was down-regulated in lico A treated HUVECs. Our data revealed that EndMT process was alleviated by lico A. Meanwhile, PI3K/AKT signaling pathway was activated in model rat of CNV and Ox-LDL-stimulated HUVECs, which can be suppressed with treatment of lico A. Our experimental results confirmed for the first time that lico A has the potential to alleviate CNV by inhibiting the endothelial-mesenchymal transition via PI3K/AKT signaling pathway.
Assuntos
Neovascularização de Coroide , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/fisiologia , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/prevenção & controle , Neovascularização de Coroide/etiologia , Lasers , Ratos Endogâmicos BNRESUMO
We aimed to explore the effect of dibazol on the ophthalmic artery (OA) and ophthalmic artery smooth muscle cells (OASMCs) of C57BL/6J mice as well as the underlying mechanisms. The OA of C57BL/6J mice was isolated under a dissecting microscope for primary OASMCs culture and myogenic tests. OASMCs were identified through morphological and immunofluorescence analyses. Morphology changes in the OASMCs were examined by staining using rhodamine-phalloidin. We performed a collagen gel contraction assay to measure the contractile and relaxant activities of the OASMCs. The molecular probe Fluo-4 AM was used to examine intracellular free Ca2+ levels ([Ca2+]in). The myogenic effects of OA were examined using wire myography. Additionally, the whole-cell patch-clamp technique was used to investigate the mechanisms underlying the relaxant effect of dibazol on L-type voltage-gated Ca2+ channels (LVGC) in isolated cells. 10-5 M dibazol significantly inhibited the contraction of OASMCs and increased the [Ca2+]in response to 30 mM KCl in a concentration-dependent manner. Dizabol had a more significant relaxant effect than 10-5 M isosorbide dinitrate (ISDN). Similarly, dibazol showed a significant dose-dependent relaxant effect on OA contraction induced by 60 mM KCl or 0.3 µM 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619). The current-voltage (I-V) curve revealed that dibazol decreased Ca2+ currents in a concentration-dependent manner. In conclusion, dibazol exerted relaxant effects on the OA and OASMCs, which may involve the inhibition of the Ca2+ influx through LVGC in the cells.
Assuntos
Artéria Oftálmica , Vasodilatação , Camundongos , Animais , Vasodilatação/fisiologia , Camundongos Endogâmicos C57BL , Contração Muscular/fisiologia , CálcioRESUMO
In this paper, a new method is proposed to efficiently generate a single intense attosecond pulse with circular polarization (CP) through the interaction of an intense driving laser with a near-critical density plasma target. The driving laser is composed of two co-rotating CP lasers with similar frequencies but different pulse widths. When the matching condition is satisfied, the combined field is modulated to a short intense pulse followed by a weak tail. The resulting laser falling edge becomes steeper than the initial sub-pulses, which induces a quick one-time oscillation of the target surface. Meanwhile, the tail guarantees the energy to be compressed simultaneously in both polarization directions to the same extent, so that a single CP attosecond pulse can be produced efficiently and robustly via our method, which has been confirmed through extensive numerical simulations. In addition, our method makes it possible to generate a single CP attosecond pulse even for multi-cycle pulses that are already available for existing laser systems. This provides a novel way to advance the investigation of chiral-sensitive light-matter interactions in attosecond scales.
RESUMO
High-order harmonics generated from the interaction between a two-color circularly polarized laser and overdense plasma is proposed analytically and investigated numerically. By mixing two circularly polarized lasers rotating in the same direction with different frequencies (ω0, 2ω0), the laser envelope is modulated to oscillate at the laser fundamental frequency while the peak intensity of each cycle becomes greater than that of the monochromatic light. This feature makes the plasma oscillate more violently and frequently under the striking of the two-color laser than the monochromatic one, thereby generating stronger harmonics and attosecond pulses. In addition, the incorporation of the 2ω0 light greatly expands the spectral width of harmonics, which facilitates the production of shorter attosecond pulses. Particle-in-cell simulations prove that under the same condition, the harmonic radiation efficiency in the two-color laser case can be improved by orders of magnitude, and isolated attosecond pulses can be even generated as a bonus in some cases.
RESUMO
Relativistic vortex laser has drawn increasing attention in the laser-plasma community owing to its potential applications in various domains, e.g., generation of energetic charged particles with orbital angular momentum (OAM), high OAM X/γ-ray emission, high harmonics generation, and strong axial magnetic-field production. However, the generation of such relativistic vortex laser is still a challenge to the current laser technology. Using micro-structure targets named axial line-focused spiral zone plate (ALFSZP), we propose a novel scheme for ultra-intense vortex laser generation. In the scheme, a relativistic Gaussian laser pulse irradiates an ALFSZP, and diffracts as it passes through the ALFSZP. Due to the focusing and radial Hilbert transform capabilities of the ALFSZP, the seed laser is converted efficiently to a vortex one which is then well focused in a tunable focal volume. Three-dimensional particle-in-cell simulations indicate that using a seed laser pulse with intensity of 1.3 × 1020 W/cm2, the vortex laser intensity achieved is as high as 1.3 × 1021 W/cm2 with the averaged angular momentum per photon up to 0.73â, promising diverse applications in various fields aforementioned.
RESUMO
Pulmonary hypertension (PH) is a chronic progressive disease characterized by pulmonary vasoconstriction and remodeling. It causes a gradual increase in pulmonary vascular resistance leading to right-sided heart failure, and may be fatal. Chronic exposure to cigarette smoke (CS) is an essential risk factor for PH group 3; however, smoking continues to be prevalent and smoking cessation is reported to be difficult. A majority of smokers exhibit PH, which leads to a concomitant increase in the risk of mortality. The current treatments for PH group 3 focus on vasodilation and long-term oxygen supplementation, and fail to stop or reverse PH-associated continuous vascular remodeling. Recent studies have suggested that pulmonary vascular endothelial dysfunction induced by CS exposure may be an initial event in the natural history of PH, which in turn may be associated with abnormal alterations in connexin (Cx) expression. The relationship between Cx and CS-induced PH development has not yet been directly investigated. Therefore, this review will describe the roles of CS and Cx in the development of PH and discuss the related downstream pathways. We also discuss the possible role of Cx in CS-induced PH. It is hoped that this review may provide new perspectives for early intervention.
Assuntos
Fumar Cigarros , Hipertensão Pulmonar , Fumar Cigarros/efeitos adversos , Conexinas/genética , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Nicotiana , Vasoconstrição , VasodilataçãoRESUMO
CONTEXT: Farrerol, a typical natural flavanone isolated from the traditional Chinese herb 'Man-shan-hong' [Rhododendron dauricum L. (Ericaceae)] with phlegm-reducing and cough-relieving properties, is widely used in China for treating bronchitis and asthma. OBJECTIVE: To present the anti-inflammatory, antioxidant, vasoactive, antitumor, and antimicrobial effects of farrerol and its underlying molecular mechanisms. METHODS: The literature was reviewed by searching PubMed, Medline, Web of Knowledge, Scopus, and Google Scholar databases between 2011 and May 2021. The following key words were used: 'farrerol,' 'flavanone,' 'anti-inflammatory,' 'antioxidant,' 'vasoactive,' 'antitumor,' 'antimicrobial,' and 'molecular mechanisms'. RESULTS: Farrerol showed anti-inflammatory effects mainly mediated via the inhibition of interleukin (IL)-6/8, IL-1ß, tumour necrosis factor(TNF)-α, NF-κB, NO, COX-2, JNK1/2, AKT, PI3K, ERK1/2, p38, Keap-1, and TGF-1ß. Farrerol exhibited antioxidant effects by decreasing JNK, MDA, ROS, NOX4, Bax/Bcl-2, caspase-3, p-p38 MAPK, and GSK-3ß levels and enhancing Nrf2, GSH, SOD, GSH-Px, HO-1, NQO1, and p-ERK levels. The vasoactive effects of farrerol were also shown by the reduced α-SMA, NAD(P)H, p-ERK, p-Akt, mTOR, Jak2, Stat3, Bcl-2, and p38 levels, but increased OPN, occludin, ZO-1, eNOS, CaM, IP3R, and PLC levels. The antitumor effects of farrerol were evident from the reduced Bcl-2, Slug, Zeb-1, and vimentin levels but increased p27, ERK1/2, p38, caspase-9, Bax, and E-cadherin levels. Farrerol reduced α-toxin levels and increased NO production and NF-κB activity to impart antibacterial activity. CONCLUSIONS: This review article provides a theoretical basis for further studies on farrerol, with a view to develop and utilise farrerol for treating of vascular-related diseases in the future.
Assuntos
Cromonas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , HumanosRESUMO
There has been very little previous research on Indo-Pacific humpback dolphins (Sousa chinensis) in the Beibu Gulf of southern China. Here, we report on the population size, habitat and ecology, threats, and overall conservation status of this putative population. 'Population size' was estimated based on photo-identification mark/recapture analysis. It was estimated to number a total of 398-444 individuals (95% CI: 393-506), with two apparently distinct groups in the Dafengjiang-Nanliujiang Estuary and at Shatian-Caotan. Movements of dolphins in the Beibu Gulf appear to be limited, with high site fidelity. These dolphins were found to occur mainly in shallow coastal waters near estuaries. The main threats are fisheries interactions (including by-catch), vessel traffic, mariculture operations, dolphin-watching tourism, and habitat degradation (including marine construction activities and large-scale land reclamation). Although the conservation status of this putative population has been considered to be better than that of other populations of the species in more northern areas of China, there is still reason for strong concern about its future, and several management recommendations are made.
Assuntos
Distribuição Animal , Comportamento Animal/fisiologia , Conservação dos Recursos Naturais , Golfinhos/fisiologia , Ecossistema , Espécies em Perigo de Extinção , Animais , China , Golfinhos/lesões , Dinâmica Populacional , Navios , Fatores de Tempo , Ferimentos e Lesões/veterináriaRESUMO
As highly social animals, Indo-Pacific humpback dolphins ( Sousa chinensis) exhibit community differentiation. Nevertheless, our understanding of the external and internal factors influencing these dynamics, as well as their spatiotemporal variations, is still limited. In the present study, variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay, China, were monitored over two distinct periods (2007-2010 and 2017-2019) to analyze the effects of habitat utilization and the composition of individuals within the population. In both periods, the population demonstrated a strikingly similar pattern of social differentiation, characterized by the division of individuals into two main clusters and one small cluster. Spatially, the two primary clusters occupied the eastern and western waters, respectively, although the core distribution area of the eastern cluster shifted further eastward between the two periods. Despite this distribution shift, the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected. A subset of 16 individuals observed in both periods, comprising 51.6% and 43.2% of the population in each respective period, emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability, especially during the 2007-2010 period. These observations suggest that the composition of dominant individuals, an internal factor, had a more substantial influence on the formation of the social network than changes in habitat use, an external factor. Consequently, the study proposes distinct conservation measures tailored to each of the two main clusters.
Assuntos
Golfinhos , Animais , Ecossistema , ChinaRESUMO
Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age-related macular degeneration (wAMD). Here, a microemulsion-doped hydrogel (Bor/PT-M@TRG) is engineered as an intravitreal depot composing of temperature-responsive hydrogel (TRG) and borneol-decorated paeoniflorin (PF) & tetramethylpyrazine (TMP)-coloaded microemulsions (Bor/PT-M). Bor/PT-M@TRG, functioning as the "ammunition depot", resides in the vitreous and continuously releases Bor/PT-M as the therapeutic "bullet", enabling deep penetration into the retina for 21 days. A single intravitreal injection of Bor/PT-M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress-induced damage in vivo. Combinational PF&TMP regulates the "reactive oxygen species/nuclear factor erythroid-2-related factor 2/heme oxygenase-1" pathway and blocks the "hypoxia inducible factor-1α/vascular endothelial growth factor" signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer and liquid chromatography-mass spectrometry techniques, they present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE-19 cells, in vivo eye balls, and ex vivo section/retina-choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor/PT-M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination for effective treatment of wAMD.
Assuntos
Pirazinas , Animais , Pirazinas/química , Pirazinas/administração & dosagem , Pirazinas/farmacologia , Pirazinas/farmacocinética , Retina/efeitos dos fármacos , Retina/metabolismo , Degeneração Macular/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Camundongos , Hidrogéis/química , Hidrogéis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Canfanos/química , Canfanos/farmacologia , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells. METHODS: Fifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01). CONCLUSIONS: Extract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Luteína/farmacologia , Degeneração Macular/prevenção & controle , Xantofilas/farmacologia , Animais , Catepsina B/metabolismo , Cistatina C/metabolismo , Feminino , Peróxido de Hidrogênio , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado Ocular/efeitos dos fármacos , Epitélio Pigmentado Ocular/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , ZeaxantinasRESUMO
Dysregulated connexin signaling is implicated in the pathophysiology of pulmonary artery hypertension (PAH). Nicotine affects pulmonary vascular remodeling. However, the potential mechanistic link between connexin signaling and nicotine-induced pulmonary artery remodeling remains unclear. We aimed to investigate the role of connexin 43 (Cx43) in pulmonary artery remodeling in nicotine-administered C57BL/6 J wild-type (WT) and Cx43 heterozygous (Cx43+/-) mice. Hemodynamic parameters and right ventricle pathology were assessed in the mice. Serum biochemical indices of hepatic and renal function were measured. The RT-PCR, immunofluorescence, and western blotting were conducted to evaluate Cx43 mRNA and protein levels. We performed histological staining to identify pulmonary arteries. Wire myography was used to examine contraction and relaxation responses in the pulmonary arteries. Pulmonary vascular permeability was assessed through Evans blue staining. Compared with the WT group, the Cx43+/- group showed lower Cx43 mRNA and protein expression in the pulmonary arteries (P < 0.01). Nicotine treatment significantly increased Cx43 expression (P < 0.01) and induced morphological changes in the pulmonary arteries (P < 0.01). Our findings suggest that Cx43 plays a crucial role in pulmonary artery reactivity and permeability in mice. Furthermore, downregulation of Cx43 expression may contribute to alterations in pulmonary artery structure and function.
Assuntos
Conexina 43 , Artéria Pulmonar , Camundongos , Animais , Conexina 43/genética , Conexina 43/metabolismo , Artéria Pulmonar/metabolismo , Regulação para Baixo , Nicotina/toxicidade , Camundongos Endogâmicos C57BL , Conexinas/genética , Conexinas/metabolismo , Remodelação Vascular , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Oxidative stress plays a critical role in age-related macular degeneration (AMD), and epithelial-mesenchymal transition (EMT) is involved in this process. The aim of this study was to investigate the protective effects of luteolin, a natural flavonoid with strong antioxidant activity, on H2O2-induced EMT in ARPE-19 cells. ARPE-19 cells were incubated with H2O2 at 200 µΜ to induce oxidative stress-associated injury. Cell viability assay showed that luteolin at 20 and 40 µM significantly promoted cell survival in H2O2-treated ARPE-19 cells. Luteolin also markedly protected ARPE-19 cells from H2O2-induced apoptosis. Cell migration assay presented that luteolin significantly reduced H2O2-induced migration in APRE-19 cells. EMT in ARPE-19 cells was detected by western blotting and immunofluorescence. The results showed that H2O2 significantly upregulated the expression of α-SMA and vimentin and downregulated the expression of ZO-1 and E-cadherin, while cells pretreated with luteolin showed a reversal. Meanwhile, the assessment of effects of luteolin on the Nrf2 pathway indicated that luteolin promoted Nrf2 nuclear translocation and upregulated the expressions of HO-1 and NQO-1. In addition, luteolin significantly increased the activities of SOD and GSH-PX and decreased intracellular levels of ROS and MDA in H2O2-treated ARPE-19 cells. Meanwhile, we observed that the expression of TGF-ß2, p-AKT, and p-GSK-3ß was upregulated in H2O2-treated ARPE-19 cells and downregulated in luteolin-treated cells, revealing that luteolin inhibited the activation of the AKT/GSK-3ß pathway. However, these effects of luteolin were all annulled by transfecting ARPE-19 cells with Nrf2 siRNA. Our current data collectively indicated that inhibition of luteolin on EMT was induced by oxidative injury in ARPE-19 cell through the Nrf2 and AKT/GSK-3ß pathway, suggesting that luteolin could be a potential drug for the treatment of dry AMD.
Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Antioxidantes/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Epitélio Pigmentado da Retina/citologia , Transdução de Sinais/efeitos dos fármacosRESUMO
In recent years, the incidence of infertility has been increasing gradually, while the natural rate of population growth is declining or even at zero growth. China is observed to enter a depth of aging society, leading to more severe infertility. Infertility patients face many predicaments, and many unreasonable behaviors existed in seeking medical diagnosis and treatment, of which the main influencing factor is economic condition. In China, Beijing has taken the lead in providing medical insurance for 16 assisted reproductive technology items. Assuming that all infertile couples with the option of assisted reproduction are treated, there would be a huge market gap. The reimbursement rate can be adjusted based on some factors within the affordable range of the medical insurance fund. Progress on infertility coverage in other countries was also reviewed. This paper cited the data of medical insurance funds in China in the recent 4 years as a reference. Based on the data, it is not currently able to cover all the costs of infertility diagnosis and treatment during the research period, but it is feasible to access selective reimbursement and subsidies for those in particular need as well as to develop some commercial insurances. There is a big gap in the application of assisted reproductive technology between China and developed countries. More comprehensive and constructive policies should be formulated countrywide to standardize the market. Assisted reproduction-related technologies and acceleration of the domestic medical apparatus and instrument replacement should be improved to reduce the cost.
Assuntos
Infertilidade , Seguro , China/epidemiologia , Estudos de Viabilidade , Humanos , Infertilidade/epidemiologia , Infertilidade/terapia , Técnicas de Reprodução AssistidaRESUMO
AIMS: The aim of this study was to develop a Diabetes Mellitus Treatment Adherence Scale (DMTAS) to fill the gap in the internationally accepted comprehensive scale. METHODS: An initial item pool for the Diabetes Mellitus Treatment Adherence Scale (DMTAS) was generated based on a review of the literature and an open-ended interview. An expert group screened this initial item pool using an item-level content validity index. Then, pilot testing with 116 participants was conducted. After removing redundant and cross-loading items by exploratory factor analysis, 630 subjects were recruited to evaluate the reliability and validity of DMTAS. Analyses included internal consistency, test-retest reliability, split-half reliability, construct validity, convergent validity, and discriminant validity analysis. RESULTS: The final DMTAS consisted of 19 items and six dimensions. The results of the exploratory factor analysis indicated that the variances of each factor explained were 23.07%, 12.28%, 9.50%, 8.25%, 7.85%, and 5.80%, and all six factors explained 66.75% of the variance in the 19 items. The items' factor loadings were all above 0.6. The results of the confirmatory factor analysis indicated that adequate fit indices (χ2 value to degrees of freedom = 3.62; root mean square error of approximation = 0.06; goodness-of-fit index = 0.92) were achieved. The Cronbach's alpha coefficient was 0.79, test-retest reliability was 0.73, and split-half reliability was 0.75. CONCLUSIONS: The DMTAS showed good validity and reliability to measure the out-of-hospital treatment adherence in patients with diabetes mellitus.
Assuntos
Diabetes Mellitus/terapia , Psicometria/métodos , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estudos de Validação como AssuntoRESUMO
This study is designed to investigate the role of novel protein kinases C (nPKC) in mediating pulmonary artery smooth muscle cells (PASMCs) proliferation in pulmonary hypertension (PH) and the underlying mechanisms. Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCdelta (PKCδ) and PKCepsilon (PKCε) and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.
Assuntos
Hipóxia Celular/fisiologia , Hipertensão Pulmonar/patologia , Miócitos de Músculo Liso , Proteína Quinase C/biossíntese , Artéria Pulmonar/patologia , Animais , Proliferação de Células , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Oncogênica v-akt/efeitos dos fármacos , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C-delta/efeitos dos fármacos , Proteína Quinase C-épsilon/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Regulação para Cima/fisiologiaRESUMO
A COVID-19 epidemic has been spreading in China and other parts of the world since December 2019. The epidemic has brought not only the risk of death from infection but also unbearable psychological pressure. We sampled college students from Changzhi medical college by using cluster sampling. They responded to a questionnaire packet that included the 7-item Generalized Anxiety Disorder Scale (GAD-7) and those inquiring the participants' basic information. We received 7,143 responses. Results indicated that 0.9% of the respondents were experiencing severe anxiety, 2.7% moderate anxiety, and 21.3% mild anxiety. Moreover, living in urban areas (OR = 0.810, 95% CI = 0.709 - 0.925), family income stability (OR = 0.726, 95% CI = 0.645 - 0.817) and living with parents (OR = 0.752, 95% CI = 0.596 - 0.950) were protective factors against anxiety. Moreover, having relatives or acquaintances infected with COVID-19 was a risk factor for increasing the anxiety of college students (OR = 3.007, 95% CI = 2.377 - 3.804). Results of correlation analysis indicated that economic effects, and effects on daily life, as well as delays in academic activities, were positively associated with anxiety symptoms (P < .001). However, social support was negatively correlated with the level of anxiety (P < .001). It is suggested that the mental health of college students should be monitored during epidemics.
Assuntos
Transtornos de Ansiedade , Ansiedade , Infecções por Coronavirus/psicologia , Saúde Mental , Pneumonia Viral/psicologia , Estudantes de Medicina , Atividades Cotidianas , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/psicologia , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Epidemias , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Risco , SARS-CoV-2 , Apoio Social , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
Oxidative stress is a critical factor in the pathology of age-related macular degeneration (AMD). Apigenin (AP) is a flavonoid with an outstanding antioxidant activity. We had previously observed that AP protected APRE-19 cells against oxidative injury in vitro. However, AP has poor water and fat solubility, which determines its low oral bioavailability. In this study, we prepared the solid dispersion of apigenin (AP-SD). The solubility and dissolution of AP-SD was significantly better than that of the original drug, so the oral bioavailability in rats was better than that of the original drug. Then, the effects of AP-SD on the retina of a model mouse with dry AMD were assessed by fundus autofluorescence (FAF), optical coherence tomography (OCT), and electron microscopy; the results revealed that AP-SD alleviated retinopathy. Further research found that AP-SD promoted the nuclear translocation of Nrf2 and increased expression levels of the Nrf2 and target genes HO-1 and NQO-1. AP-SD enhanced the activities of SOD and GSH-Px and decreased the levels of ROS and MDA. Furthermore, AP-SD upregulated the expressions of p62 and LC3II in an Nrf2-dependent manner. However, these effects of AP-SD were observed only in the retina of Nrf2 WT mice, not in Nrf2 KO mice. In addition, the therapeutic effect of AP-SD was dose dependent, and AP did not work. In conclusion, AP-SD significantly enhanced the bioavailability of the original drug and reduced retinal oxidative injury in the model mouse of dry AMD in vivo. The results of the underlying mechanism showed that AP-SD upregulated the expression of antioxidant enzymes through the Nrf2 pathway and upregulated autophagy, thus inhibiting retinal oxidative damage. AP-SD may be a potential compound for the treatment of dry AMD.
Assuntos
Antioxidantes/uso terapêutico , Apigenina/uso terapêutico , Degeneração Macular/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Retina/metabolismo , Animais , Autofagia , Células Cultivadas , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Retina/patologia , Transdução de SinaisRESUMO
The morphological characteristics of tendons have been thoroughly evaluated via microscopy. Optical microscopy and electron microscopy are the most commonly used techniques for tendon tissue observation. According to the principles of both microscopy types, preparation and evaluation methods vary. Simple optical microscopy is commonly used in the observation of cells and extracellular matrix, and many stains, including hematoxylin-eosin, Van Gieson, Prussian blue, Alcian blue, and toluidine blue, are used for evaluating cells, collagen fiber arrangement, and noncollagenous proteins. Histological scoring systems have been used in many studies for semi-quantification. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are the most commonly used electron microscopy types, and special consideration is needed for the fixation and embedding protocols. Glutaraldehyde followed by osmium is most commonly used in the chemical fixation of tendon tissue, followed by epoxy resin embedment. Longitudinal sections captured in SEM images show the arrangement of collagen fibrils and the cells and lipid drops among them, while cross sections captured in TEM images show the diameter and distribution of collagen fibrils. SEM and TEM are used together for comprehensive evaluations. This mini review is focused on the preparation methodology and related evaluation indexes for the morphological evaluation of tendons.