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1.
Artigo em Inglês | MEDLINE | ID: mdl-35532366

RESUMO

Loving-kindness and compassion meditation (LKCM) was a promising intervention for improving life satisfaction, but previous findings have been inconsistent. The current study provides a systematic review and meta-analysis, including 23 empirical studies on LKCM with life satisfaction as an outcome variable. The primary meta-analysis indicated that LKCM significantly enhanced life satisfaction in pre-post design (g = 0.312, k = 15, n = 451), but the significance disappeared in the additional meta-analysis based on randomized controlled trials (g = 0.106, k = 6, n = 404). Moderator analyses found significant effects for type of control (i.e., the effects of LKCM were inferior to active control group, but superior to waitlist condition), but not for other moderators (i.e., participant type, previous meditation experience, specific protocol, components of LKCM, combination with mindfulness mediation, and intervention length). Narrative review identified self-compassion and positive emotions as important mediators. The practice time of LKCM had indirect but not direct association with life satisfaction. The findings supported that LKCM is promising in increasing life satisfaction, but more studies are needed to investigate the effects with more rigorous designs. Future studies should investigate other potential mechanisms and clarify whether LKCM change the reality or the perception of life.

2.
Chemosphere ; 301: 134780, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500633

RESUMO

Active samplers are widely used in the quantification of gaseous semi-volatile organic compounds (SVOCs). A sampling tube is often assembled upstream of the sampler, especially in the active samplers used for separating the particle-phase and gas-phase SVOCs and in the newly-designed active sampler based on solid-phase microextraction (SPME). However, gaseous SVOCs can be easily adsorbed by the sampling tube, which may induce significant errors to the quantitative results. Taking the SPME-based active sampler as an example, a mass-transfer model was developed to characterize the sampling-tube loss of gaseous SVOCs. Experiments involving six SVOCs were conducted. The model predictions (with a best-fit surface/air partition coefficient of SVOCs) were found to be consistent with the measurements. Both model predictions and experimental data indicated that the measured concentrations were significantly lower than the actual concentration (around 60% lower) due to the sampling-tube loss. The duration of sampling-tube loss (τe, minutes to days) varied with the volatility of SVOCs (vapor pressure, Vp), i.e., log τe linearly increased as increasing log Vp. The relationship could be helpful for determining the sampling strategies to eliminate (reduce) the effects of sampling-tube loss according to the volatility of SVOCs. The above conclusions may be also applicable for other active samplers of gaseous SVOCs. However, further studies are required to quantify the effects of sampling-tube loss for other active samplers due to the difference in the size and shape of the sampling tube between them and the SPME-based active sampler. The corresponding mass-transfer model and experimental procedure may require adjustment as appropriate.

3.
Thorac Cancer ; 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35569920

RESUMO

BACKGROUND: Although it has a poor prognosis, patients with lung adenocarcinoma (LUAD) have a relatively higher 5-year survival period. Thus, it is necessary to identify effective prognostic markers to evaluate the effect of early treatment. RS1 gene encodes retinoschisin, a key protein in congenital retinoschisis, while few studies have been reported on the association between RS1 and cancer prognosis. METHODS: We performed bioinformatic analyses based on the data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases to demonstrate the expression level of RS1 was related to the LUAD prognosis and our findings were verified in-vitro and clinical samples. Then, we explored the potential mechanism of how RS1 expression influenced the prognosis of LUAD. RESULTS: Compared with normal tissues, the RS1 expression was significantly lower in tumor tissues. The Multivariate Cox regression model showed that RS1 could be used as an independent prognostic indicator. Furthermore, we found significant differences in immune cell infiltration between RS1 high and low expression groups, and the proteasome pathway was found enriched in RS1 low expression samples. CONCLUSION: In conclusion, our study suggests that RS1 is a novel prognostic biomarker for LUAD. Differences in immune cell infiltration and signaling pathways may contribute to the poor prognosis of LUAD caused by low RS1 expression.

4.
Front Pharmacol ; 13: 875330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517800

RESUMO

In the past few decades, several gene mutations, including the anaplastic lymphoma kinase, epidermal growth factor receptor, ROS proto-oncogene 1 and rat sarcoma viral oncogene homolog (RAS), have been discovered in non-small cell lung cancer (NSCLC). Kirsten rat sarcoma viral oncogene homolog (KRAS) is the isoform most frequently altered in RAS-mutated NSCLC cases. Due to the structural and biochemical characteristics of the KRAS protein, effective approaches to treating KRAS-mutant NSCLC still remain elusive. Extensive recent research on KRAS-mutant inhibitors has made a breakthrough in identifying the covalent KRASG12C inhibitor as an effective agent for the treatment of NSCLC. This review mainly concentrated on introducing new covalent KRASG12C inhibitors like sotorasib (AMG 510) and adagrasib (MRTX 849); summarizing inhibitors targeting the KRAS-related upstream and downstream effectors in RAF/MEK/ERK pathway and PI3K/AKT/mTOR pathway; exploring the efficacy of immunotherapy and certain emerging immune-related therapeutics such as adoptive cell therapy and cancer vaccines. These inhibitors are being investigated in clinical trials and have exhibited promising effects. On the other hand, naturally extracted compounds, which have exhibited safe and effective properties in treating KRAS-mutant NSCLC through suppressing the MAPK and PI3K/AKT/mTOR signaling pathways, as well as through decreasing PD-L1 expression in preclinical studies, could be expected to enter into clinical studies. Finally, in order to confront the matter of drug resistance, the ongoing clinical trials in combination treatment strategies were summarized herein.

5.
BMC Med Res Methodol ; 22(1): 113, 2022 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-35436861

RESUMO

BACKGROUND: Traditional mediation analysis typically examines the relations among an intervention, a time-invariant mediator, and a time-invariant outcome variable. Although there may be a total effect of the intervention on the outcome, there is a need to understand the process by which the intervention affects the outcome (i.e., the indirect effect through the mediator). This indirect effect is frequently assumed to be time-invariant. With improvements in data collection technology, it is possible to obtain repeated assessments over time resulting in intensive longitudinal data. This calls for an extension of traditional mediation analysis to incorporate time-varying variables as well as time-varying effects. METHODS: We focus on estimation and inference for the time-varying mediation model, which allows mediation effects to vary as a function of time. We propose a two-step approach to estimate the time-varying mediation effect. Moreover, we use a simulation-based approach to derive the corresponding point-wise confidence band for the time-varying mediation effect. RESULTS: Simulation studies show that the proposed procedures perform well when comparing the confidence band and the true underlying model. We further apply the proposed model and the statistical inference procedure to data collected from a smoking cessation study. CONCLUSIONS: We present a model for estimating time-varying mediation effects that allows both time-varying outcomes and mediators. Simulation-based inference is also proposed and implemented in a user-friendly R package.


Assuntos
Modelos Estatísticos , Negociação , Causalidade , Simulação por Computador , Humanos , Tempo
6.
Front Nutr ; 9: 790519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399670

RESUMO

Food insecurity (FI) is a dynamic phenomenon, and its association with daily affect is unknown. We explored the association between daily FI and affect among low-income adults during a 2-seasonal-month period that covered days both pre- and during the COVID-19 pandemic. A total of 29 healthy low-income adults were recruited during fall in 2019 or 2020, 25 of whom were followed in winter in 2020 or 2021. Daily FI (measured once daily) and affect (measured 5 times daily) were collected over the 2nd-4th week in each month. Time-Varying-Effect-Models were used to estimate the association between daily FI and positive/negative affect (PA/NA). Overall, 902 person-days of daily-level data were collected. Daily FI was associated with lower PA in the 3rd and 4th week of fall and winter and with higher NA in the second half of winter months. Similar patterns of FI-affect relations were found pre- and during COVID-19 in the second half of a given month, while unique patterns of positive affect scores in the 2nd week and negative scores in the 1st week were only observed during COVID days. Our study supports a time-varying association between FI and affect in low-income adults. Future large studies are needed to verify the findings; ultimately, better understanding such associations may help identify, target, and intervene in food insecure adults to prevent adverse mental health outcomes.

7.
Bioact Mater ; 18: 267-283, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387156

RESUMO

Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute. Therefore, the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity. However, the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved. Moreover, in order to achieve vascularized bone regeneration, alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost. In this study, a novel injectable self-healing hydrogel system (GMO hydrogel) loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect. The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities, which led to an excellent injectability and fittability. By photopolymerization of the enclosed GelMA, GMO hydrogel was further strengthened and thus more suitable for bone regeneration. Besides, the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction, leading to desired releasing profiles. In vitro, this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs. In vivo, KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria. Overall, the KP and QK loaded GMO hydrogel was injectable and self-healing, which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach.

8.
Front Plant Sci ; 13: 850090, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360302

RESUMO

Dendrobium huoshanense is both a traditional herbal medicine and a plant of high ornamental and medicinal value. We used transcriptomics and metabolomics to investigate the effects of growth year on the secondary metabolites of D. huoshanense stems obtained from four different years of cultivation. In this study, a total of 428 differentially accumulated metabolites (DAMs) and 1802 differentially expressed genes (DEGs) were identified. The KEGG enrichment analysis of DEGs and DAMs revealed significant differences in "Flavonoid biosynthesis", "Phenylpropanoid biosynthesis" and "Flavone and flavonol biosynthesis". We summarize the biosynthesis pathway of flavonoids in D. huoshanense, providing new insights into the biosynthesis and regulation mechanisms of flavonoids in D. huoshanense. Additionally, we identified two candidate genes, FLS (LOC110107557) and F3'H (LOC110095936), which are highly involved in flavonoid biosynthesis pathway, by WGCNA analysis. The aim of this study is to investigate the effects of growth year on secondarily metabolites in the plant and provide a theoretical basis for determining a reasonable harvesting period for D. huoshanense.

9.
Front Pharmacol ; 13: 802228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237162

RESUMO

Background: Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide epidemic and claimed millions of lives. Accumulating evidence suggests that cytokines storms are closely associated to COVID-19 severity and death. Here, we aimed to explore the key factors related to COVID-19 severity and death, especially in terms of the male patients and those in western countries. Methods: To clarify whether inflammatory cytokines have role in COVID-19 severity and death, we systematically searched PubMed, Embase, Cochrane library and Web of Science to identify related studies with the keywords "COVID-19″ and "cytokines". The data were measured as the mean with 95% confidence interval (CI) by Review Manager 5.3 software. The risk of bias was assessed for each study using appropriate checklists. Results: We preliminarily screened 13,468 studies from the databases. A total of 77 articles with 13,468 patients were ultimately included in our study. The serum levels of cytokines such as interleukin-6 (IL-6), IL-10, interleukin-2 receptor (IL-2R), tumor necrosis factor (TNF)-α, IL-1ß, IL-4, IL-8 and IL-17 were higher in the severity or death group. Notably, we also found that the circulating levels of IL-6, IL-10, IL-2R and TNF-α were significantly different between males and females. The serum levels of IL-6, IL-10, IL-2R and TNF-α were much higher in males than in females, which implies that the increased mortality and severity in males was partly due to the higher level of these cytokines. Moreover, we found that in the severe and non-survivor groups, European patients had elevated levels of IL-6 compared with Asian patients. Conclusion: These large-scale data demonstrated that the circulating levels of IL-6, IL-10, IL-2R, IL-1ß, IL-4, IL-8 and IL-17 are potential risk factors for severity and high mortality in COVID-19. Simultaneously, the upregulation of these cytokines may be driving factors for the sex and region predisposition.

10.
Toxicol Appl Pharmacol ; 441: 115988, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35307375

RESUMO

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations account for 35% of the genetic alterations in non-small cell lung cancer (NSCLC). The Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is closely involved in RAS downstream pathways and development of many tumors by affecting cell proliferation, differentiation, and immunity. Targeting SHP2 with small molecules may be a promising avenue for the treatment of KRAS-mutant (mut) NSCLC. Herein, hexachlorophene (HCP) was identified as a SHP2 inhibitor with an IC50 value of 5.63 ± 0.75 µM through screening of the FDA-approved drug library. HCP specifically inhibited SHP2 rather than other phosphatases. Molecular docking showed that HCP displayed an orientation favorable for nucleophilic attack in the catalytic domain of SHP2. HCP suppressed viability of multiple KRAS-mut and KRAS-wild type cells and induced senescence and apoptosis in KRAS-mut cells. Moreover, HCP reversed epithelial-mesenchymal transition to suppress metastasis in KRAS-mut cells, and inhibited the RAS/MEK/ERK and PI3K/AKT signaling pathways by suppression of SHP2 phosphorylation and formation SHP2/Grb2/Gab1/SOS1 complex. In summary, HCP can act as a specific SHP2 inhibitor to inhibit KRAS-mut NSCLC cell proliferation and metastasis and induce senescence through suppression of the RAF/MEK/ERK and PI3K/AKT pathways. HCP warrants further investigation as a new compound skeleton for the development of selective SHP2 inhibitors for the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Hexaclorofeno , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Mutação , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais
11.
Immunol Lett ; 244: 28-39, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35288207

RESUMO

Caspase-1 is an integral regulator of innate immunity, which plays a key role in inflammasome activation and the release of pro-inflammatory cytokines. The development of novel non-peptidic small molecule caspase-1 inhibitors is an important strategy for antagonizing excessively activated caspase-1 induced by inflammatory diseases, including gouty arthritis. In the present study, we identified 63 caspase-1 inhibitors, with different structures and potencies, from bioactive compound libraries. Among them, NSC697923 potently inhibited the enzymatic activity of caspase-1, with an IC50 value of 1.737 µM. This compound adopted a favorable conformation in the active pocket of caspase-1. Furthermore, NSC697923 potently decreased mature interleukin (IL)-1ß secretion in macrophages stimulated by lipopolysaccharide plus nigericin, ATP, and monosodium urate crystal. NSC697923 also inhibited NLRP3 protein expression by suppressing the NF-κB signaling pathway and the interaction between receptor interacting protein-2 (RIP2) and pro-caspase-1, thereby blocking the priming of the NLRP3 inflammasome. In addition, NSC697923 significantly inhibited caspase-1 mediated gasdermin D cleavage and pyroptosis in macrophages. In an animal model of gouty arthritis, NSC697923 effectively inhibited joint swelling, IL-1ß release, and NLRP3 inflammasome activation. Our results indicate that NSC697923 can effectively suppress NLRP3 inflammasome activation by inhibiting caspase-1, thus warranting further investigation as a potential therapeutic for treating NLRP3 inflammasome-related diseases.


Assuntos
Artrite Gotosa , Gota , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Caspase 1/metabolismo , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose
12.
Photochem Photobiol ; 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313014

RESUMO

This paper presents room temperature nanoseconds to milliseconds time-resolved spectra and kinetics of the intermediate states and species of bovine and carp fish rhodopsin visual pigments, which also contained ~5% cone pigments. The nanoseconds to milliseconds range cover all the major intermediates in the visual phototransduction process except the formation of bathorhodopsin intermediate which occurs at the femtosecond time scale. The dynamics of these visual pigment intermediates are initiated by excitation with a 532 nm nanosecond laser pulse. The recorded differences between bovine and carp rhodopsin time-resolved spectra of the formation and decay kinetics of their intermediates are presented and discussed. The data show that the carp samples batho intermediate decays faster, nearly by a factor of three, compared to the bovine samples. The formation and decay spectra and kinetics of rhodopsin outer segments and extracted rhodopsin inserted in buffer solution were found to be identical, with very small differences between them in the decay lifetimes of bathorhodopsin and formation of lumirhodopsin.

13.
Nutr J ; 21(1): 19, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35331249

RESUMO

BACKGROUND: Food insecurity (FI) is a dynamic phenomenon. Experiences of daily FI may impact dietary outcomes differently within a given month, across seasons, and before or during the COVID-19 pandemic. OBJECTIVES: The aims of this study were to investigate the association of short-term FI with dietary quality and energy 1) over six weeks in two seasonal months and 2) before and during the COVID-19 pandemic. METHODS: Using an ecological momentary assessment framework on smartphones, this study tracked daily FI via the 6-item U.S. Adult Food Security Survey Module and dietary intake via food diaries in 29 low-income adults. A total of 324 person-days of data were collected during two three-week long waves in fall and winter months. Generalized Estimating Equation models were applied to estimate the daily FI-diet relationship, accounting for intrapersonal variation and covariates. RESULTS: A one-unit increase in daily FI score was associated with a 7.10-point (95%CI:-11.04,-3.15) and 3.80-point (95%CI: -6.08,-1.53) decrease in the Healthy Eating Index-2015 (HEI-2015) score in winter and during COVID-19, respectively. In winter months, a greater daily FI score was associated with less consumption of total fruit (-0.17 cups, 95% CI: -0.32,-0.02), whole fruit (-0.18 cups, 95%CI: -0.30,-0.05), whole grains (-0.57 oz, 95%CI: -0.99,-0.16) and higher consumption of refined grains (1.05 oz, 95%CI: 0.52,1.59). During COVID-19, elevated daily FI scores were associated with less intake of whole grains (-0.49 oz, 95% CI: -0.88,-0.09), and higher intake of salt (0.34 g, 95%CI: 0.15,0.54). No association was observed in fall nor during the pre-COVID-19 months. No association was found between daily FI and energy intake in either season, pre-COVID 19, or during-COVID-19 months. CONCLUSION: Daily FI is associated with compromised dietary quality in low-income adults in winter months and during the COVID-19 period. Future research should delve into the underlying factors of these observed relationships.


Assuntos
COVID-19 , Adulto , COVID-19/epidemiologia , Dieta , Ingestão de Energia , Insegurança Alimentar , Humanos , Pandemias , Estações do Ano
14.
Artigo em Inglês | MEDLINE | ID: mdl-35073262

RESUMO

Ultrasound medical imaging is an entrenched and powerful tool for medical diagnosis. Image quality in ultrasound is mainly dependent on performance of piezoelectric transducer elements, which is further related to the electromechanical performance of the constituent piezoelectric materials. With rising need for piezoelectric materials with better performance and low-cost, a highly <001> textured piezo-ceramic, Pb (Mg1/3Nb2/3)O3-Pb(Zr,Ti)O3, have been developed. Recently, textured ceramic materials can be produced at low cost and exhibit high piezoelectric strain constants and large electromechanical coupling coefficients. In this work, 15-MHz ultrasonic transducers with an effective aperture of 2.5 mm in diameter based on these highly <001> textured ceramics has been successfully fabricated. The fabricated transducers achieved a central frequency of 15 MHz, a fractional bandwidth of 67% (at -6 dB), a high effective electromechanical coupling coefficient, keff, of 0.55, and low insertion loss (IL) of 21 dB. Ex vivo ultraonic imaging of a porcine eyeball was used to assess the tomography quality of the transducer. The results show that utilized textured ceramic has a great potential in developing ultrasonic devices for biomedical imaging purposes.

16.
Exp Biol Med (Maywood) ; 247(6): 519-526, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34648358

RESUMO

Current treatments for meibomian gland dysfunction have several limitations, creating a necessity for other advanced treatment options. The purpose of this study is to determine the effectiveness of focused ultrasound stimulation for the treatment of dry eye disease caused by meibomian gland dysfunction. An in vivo study of nine Dutch Belted rabbits was conducted with focused ultrasound stimulation of the meibomian glands. A customized line-focused ultrasonic transducer was designed for treatment. Fluorescein imaging, Schirmer's test, and Lipiview II ocular interferometer were used to quantify outcomes from three aspects: safety, tear production, and lipid layer thickness. Both tear secretion and lipid layer thickness improved following ultrasound treatment. Five to 10 min after the ultrasound treatment, the mean values of lipid layer thickness increased from 55.33 ± 11.15 nm to 95.67 ± 22.77 nm (p < 0.05), while the mean values measured with the Schirmer's test increased from 2.0 ± 2.3 to 7.2 ± 4.3 (p < 0.05). Positive effects lasted more than three weeks. Adverse events such as redness, swelling, and mild burn, occurred in two rabbits in preliminary experiments when the eyelids sustained a temperature higher than 42°C. No serious adverse events were found. The results suggest that ultrasound stimulation of meibomian glands can improve both tear production and lipid secretion. Ultimately, ultrasound stimulation has the potential to be an option for the treatment of evaporative dry eye disease caused by meibomian gland dysfunction.


Assuntos
Síndromes do Olho Seco , Disfunção da Glândula Tarsal , Animais , Síndromes do Olho Seco/terapia , Lipídeos , Glândulas Tarsais , Coelhos , Lágrimas/fisiologia
17.
IEEE Trans Biomed Eng ; 69(5): 1585-1594, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34652993

RESUMO

OBJECTIVE: The ocular vascular system plays an important role in preserving the visual function. Alterations in either anatomy or hemodynamics of the eye may have adverse effects on vision. Thus, an imaging approach that can monitor alterations of ocular blood flow of the deep eye vasculature ranging from capillary-level vessels to large supporting vessels would be advantageous for detection of early stage retinal and optic nerve diseases. METHODS: We propose a super-resolution ultrasound localization microscopy (ULM) technique that can assess both the microvessel and flow velocity of the deep eye with high resolution. Ultrafast plane wave imaging was acquired using an L22-14v linear array on a high frequency Verasonics Vantage system. A robust microbubble localization and tracking technique was applied to reconstruct ULM images. The experiment was first performed on pre-designed flow phantoms in vitro and then tested on a New Zealand white rabbit eye in vivo calibrated to various intraocular pressures (IOP) - 10 mmHg, 30 mmHg and 50 mmHg. RESULTS: We demonstrated that retinal/choroidal vessels, central retinal artery, posterior ciliary artery, and vortex vein were all visible at high resolution. In addition, reduction of vascular density and flow velocity were observed with elevated IOPs. CONCLUSION: These results indicate that super-resolution ULM is able to image the deep ocular tissue while maintaining high resolution that is comparable with optical coherence tomography angiography. SIGNIFICANCE: Capability to detect subtle changes of blood flow may be clinically important in detecting and monitoring eye diseases such as glaucoma.


Assuntos
Microscopia , Vasos Retinianos , Animais , Velocidade do Fluxo Sanguíneo , Hemodinâmica , Microbolhas , Coelhos , Fluxo Sanguíneo Regional/fisiologia , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica
18.
Phytomedicine ; 95: 153786, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34785104

RESUMO

BACKGROUND: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development. PURPOSE: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC). METHODS: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model. RESULTS: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle. CONCLUSION: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Emodina , Neoplasias Pulmonares , Fosfolipases A2 Secretórias , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Regulação para Baixo , Emodina/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico
19.
Gait Posture ; 91: 297-305, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798421

RESUMO

BACKGROUND: Given that cerebral palsy is a lifelong condition, continuous motor training is necessary to correct abnormal posture and patterns to improve functional performance. OBJECTIVE: To explore the essential features of virtual motor training and identify its effects on the activities of daily living, hand grip function, and gross motor function among children with cerebral palsy. METHODS: Ten databases were systematically searched for randomized controlled trials from inception until October 15, 2019. Studies with a randomized controlled trials design, children with cerebral palsy, comparisons of virtual motor training with other interventions, and activities of daily living, hand grip, and gross motor function outcomes were included. Subgroup analyses and meta-regression were performed. The effect size was assessed using random-effects meta-analysis and evaluated by using Hedges' g. Random effects univariate meta-regression model was used to examine the association of covariates with intervention effectiveness. RESULTS: Seventeen randomized controlled trials with 853 participants were included. Meta-analysis indicated that the virtual motor training had significant positive effects on activities of daily living (g = 0.31, 95% confidence interval, CI = 0.10, 0.51), grip (g = 0.40, 95% CI = 0.08, 0.71), and gross motor (g = 0.71, 95% CI = 0.43, 0.99) function. Univariate random-effects meta-regression analysis indicated an increase in activities of daily living scores for motion capture systems that used depth imaging compared with those that used digital imaging. SIGNIFICANCE: Our systematic review indicated that virtual motor function may significantly improve ADLs, hand grip, and gross motor functions among children with cerebral palsy.


Assuntos
Atividades Cotidianas , Paralisia Cerebral , Criança , Força da Mão , Humanos , Desempenho Físico Funcional , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão
20.
Phytomedicine ; 96: 153831, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34794861

RESUMO

BACKGROUND: Currently, the identification of accurate biomarkers for the diagnosis of patients with early-stage lung cancer remains difficult. Fortunately, metabolomics technology can be used to improve the detection of plasma metabolic biomarkers for lung cancer. In a previous study, we successfully utilised machine learning methods to identify significant metabolic markers for early-stage lung cancer diagnosis. However, a related research platform for the investigation of tumour metabolism and drug efficacy is still lacking. HYPOTHESIS/PURPOSE: A novel methodology for the comprehensive evaluation of the internal tumour-metabolic profile and drug evaluation needs to be established. METHODS: The optimal location for tumour cell inoculation was identified in mouse chest for the non-traumatic orthotopic lung cancer mouse model. Microcomputed tomography (micro-CT) was applied to monitor lung tumour growth. Proscillaridin A (P.A) and cisplatin (CDDP) were utilised to verify the anti-lung cancer efficacy of the platform. The top five clinically valid biomarkers, including proline, L-kynurenine, spermidine, taurine and palmitoyl-L-carnitine, were selected as the evaluation indices to obtain a suitable lung cancer mouse model for clinical metabolomics research by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The platform was successfully established, achieving 100% tumour development rate and 0% surgery mortality. P.A and CDDP had significant anti-lung cancer efficacy in the platform. Compared with the control group, four biomarkers in the orthotopic model and two biomarkers in the metastatic model had significantly higher abundance. Principal component analysis (PCA) showed a significant separation between the orthotopic/metastatic model and the control/subcutaneous/KRAS transgenic model. The platform was mainly involved in arginine and proline metabolism, tryptophan metabolism, and taurine and hypotaurine metabolism. CONCLUSION: This study is the first to simulate clinical metabolomics by comparing the metabolic phenotype of plasma in different lung cancer mouse models. We found that the orthotopic model was the most suitable for tumour metabolism. Furthermore, the anti-tumour drug efficacy was verified in the platform. The platform can very well match the clinical reality, providing better lung cancer diagnosis and securing more precise evidence for drug evaluation in the future.


Assuntos
Neoplasias Pulmonares , Preparações Farmacêuticas , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Metabolômica , Camundongos , Espectrometria de Massas em Tandem , Microtomografia por Raio-X
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