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1.
BMC Cancer ; 24(1): 95, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233827

RESUMO

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcopenia , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Sarcopenia/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Eritrócitos/patologia , Curva ROC , Prognóstico
2.
Int J Med Sci ; 20(2): 225-231, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36794159

RESUMO

Pre-B-cell leukemia transcription factor 1 (PBX1) proteins are a subfamily of evolutionarily conserved atypical homeodomain transcription factors belonging to the superfamily of triple amino acid loop extension homeodomain proteins. PBX family members play crucial roles in the regulation of various pathophysiological processes. This article reviews the research progress on PBX1 in terms of structure, developmental function, and regenerative medicine. The potential mechanisms of development and research targets in regenerative medicine are also summarized. It also suggests a possible link between PBX1 in the two domains, which is expected to open up a new field for future exploration of cell homeostasis, as well as the regulation of endogenous danger signals. This would provide a new target for the study of diseases in various systems.


Assuntos
Proteínas de Homeodomínio , Medicina Regenerativa , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Aminoácidos
3.
Biotechnol Bioeng ; 119(6): 1556-1566, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35141878

RESUMO

Escherichia coli O157:H7 have previously been associated with disease outbreaks associated with leafy green vegetables. However, the physical mechanisms that determine the spatial organization of bacteria onto leafy greens are still not clear. Microfluidics with embedded trichome-mimicking microposts were employed to investigate the role of shear flow and configuration of trichomes on E. coli O157:H7 microcolonization. We characterized the three-dimensional microcolonization of green fluorescent protein (GFP)-tagged E. coli O157:H7 using multiphoton fluorescence microscopy and compared their differences under static (no flow; incubated for 36 h at 37°C) and fluid shear conditions (750 nl/min for 36 h at 37°C). For micropatterned trichome arrays, we demonstrated that natural wax-mixed polydimethylsiloxane retains similar topographies and contact angles to the surface of trichome-bearing leafy greens. Our results showed that E. coli O157:H7 under fluid shear stress aligned their colonization parallel to the direction of flow. In a static condition, their colonization had no preferential alignment, with statistically similar angular distributions in all directions. In addition, depending on dimensions of the trichome arrays and flow conditions, different bacterial microcolonization patterns grew radially from initial attachment; they formed into filamentous structures and developed into bridges by surface hydrophobicity and flow-induced shear with a nutrient-rich medium. Collectively, these results demonstrate how the consequences of bacterial colonization in response to shear flow can affect pathogenic bacterial contamination of leafy greens and biofilm architectures.


Assuntos
Escherichia coli O157 , Contagem de Colônia Microbiana , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Microfluídica , Folhas de Planta , Tricomas
4.
BMC Gastroenterol ; 22(1): 288, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668355

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer. HCC and ICC differ in treatment and prognosis, warranting an effective differential diagnosis between them. This study aimed to explore the clinical value of mean platelet volume (MPV) to discriminate between HCC and ICC. MATERIAL/METHODS: We performed a retrospective analysis of ICC and HCC patients who were from the Harbin Medical University Cancer Hospital, China. Logistic regression analysis was used to identify the independent factors for the differentiation of HCC and ICC. A receiver operating characteristic curve was built to evaluate the diagnostic performance of the potential model. An independent validation study was performed to validate the diagnostic ability. RESULTS: ICC patients were detected in 146 out of 348 patients in the primary cohort. MPV levels were decreased in ICC patients compared with those in HCC patients. Logistic regression analysis revealed that MPV was an independent factor in distinguishing HCC from ICC. A combination of sex, hepatitis B surface antigen, MPV, alpha-fetoprotein, and carbohydrate antigen 19-9 demonstrated a good capability to differentiate HCC from ICC. Similar results were achieved in the validation cohort. CONCLUSIONS: MPV may be a new marker to help distinguish ICC from HCC. Further validation studies are required.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Volume Plaquetário Médio , Estudos Retrospectivos
5.
PLoS Genet ; 15(7): e1007655, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31356596

RESUMO

Circadian clocks control the timing of animal behavioral and physiological rhythms. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210KO) exhibit a dramatic 2 hrs phase advance of evening anticipatory behavior. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3' UTR of Fas2 (Fas2ΔmiR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Drosophila melanogaster/fisiologia , Locomoção , MicroRNAs/genética , Regiões 3' não Traduzidas , Animais , Sistemas CRISPR-Cas , Ritmo Circadiano , Escuridão , Drosophila melanogaster/genética , Técnicas de Inativação de Genes , Mutação
6.
PLoS Genet ; 15(10): e1008474, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658266

RESUMO

Circadian clocks control daily rhythms in behavior and physiology. In Drosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons generating locomotor rhythms. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify the Drosophila SWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM in circadian neurons eliminates morning anticipatory activity under light dark cycle and impairs behavioral rhythmicity in constant darkness. Interestingly, the two major splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion mainly leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period without affecting the circadian rhythmicity. Both DOM-A and DOM-B bind to the promoter regions of key pacemaker genes period and timeless, and regulate their protein expression. However, we identify that only DOM-A is required for the maintenance of sLNvs and transcription of pdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that two splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance.


Assuntos
Relógios Biológicos/genética , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Fatores de Transcrição/genética , Núcleos Ventrais do Tálamo/fisiologia , Processamento Alternativo , Animais , Animais Geneticamente Modificados , Técnicas de Observação do Comportamento , Comportamento Animal , Proteínas de Drosophila/metabolismo , Feminino , Masculino , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/metabolismo , Núcleos Ventrais do Tálamo/citologia
7.
Appl Opt ; 59(25): 7567-7573, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902456

RESUMO

In this paper, a reflector antenna design method is proposed to improve transmission efficiency and control output intensity distribution. Primary and secondary mirrors are constructed segment by segment using a numerical method according to the law of energy conservation, the vector theory of reflection, and Fermat's principle that the optical path length of each ray must be equal. To verify the effectiveness and practicability of this method, an example of an antenna with the prescribed intensity distribution of the output beam is given. The transmission efficiency of the antenna system designed by this method reaches 100% in theory. The effects of output intensity distribution and deviation on transmission efficiency were also analyzed. We believe that the results show that the proposed method is a highly efficient approach to the design of a freeform reflector antenna to improve transmission efficiency and control the output intensity distribution.

8.
Soft Matter ; 15(24): 4782-4786, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31107490

RESUMO

A new process for simultaneous generation and positioning of microdroplets within a single step named oblique interface shearing (OIS) is reported based on the observation that liquid microdroplets generated by vibrating a thin capillary across the air-liquid interface at an oblique angle exhibit notable lateral displacements. An analytical model is established to describe the lateral droplet displacement induced by the Stokes drift effect. The dependency of the lateral displacement on typical operating parameters allows for on-demand droplet positioning while they are produced. The efficacy of the process is validated through delivering microdroplets with the same size to different positions as well as size-dependent positioning of these microdroplets.

9.
J Biol Chem ; 292(44): 18270-18280, 2017 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-28924048

RESUMO

Scorpion toxins can kill other animals by inducing paralysis and arrhythmia, which limits the potential applications of these agents in the clinical management of diseases. Antitumor-analgesic peptide (AGAP), purified from Buthus martensii Karsch, has been proved to possess analgesic and antitumor activities. Trp38, a conserved aromatic residue of AGAP, might play an important role in mediating AGAP activities according to the sequence and homology-modeling analyses. Therefore, an AGAP mutant, W38G, was generated, and effects of both AGAP and the mutant W38G were examined by whole-cell patch clamp techniques on the sodium channels hNav1.4 and hNav1.5, which were closely associated with the biotoxicity of skeletal and cardiac muscles, respectively. The data showed that both W38G and AGAP inhibited the peak currents of hNav1.4 and hNav1.5; however, W38G induced a much weaker inhibition of both channels than AGAP. Accordingly, W38G exhibited much less toxic effect on both skeletal and cardiac muscles than AGAP in vivo The analgesic activity of W38G and AGAP were verified in vivo as well, and W38G retained analgesic activity similar to AGAP. Inhibition to both Nav1.7 and Nav1.8 was involved in the analgesic mechanism of AGAP and W38G. These findings indicated that Trp38 was a key amino acid involved in the biotoxicity of AGAP, and the AGAP mutant W38G might be a safer alternative for clinical application because it retains the analgesic efficacy with less toxicity to skeletal and cardiac muscles.


Assuntos
Analgésicos não Narcóticos/efeitos adversos , Antineoplásicos/efeitos adversos , Proteínas de Artrópodes/efeitos adversos , Mutação , Peptídeos/efeitos adversos , Venenos de Escorpião/efeitos adversos , Bloqueadores do Canal de Sódio Disparado por Voltagem/efeitos adversos , Substituição de Aminoácidos , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/farmacologia , Analgésicos não Narcóticos/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/farmacologia , Proteínas de Artrópodes/uso terapêutico , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Camundongos , Canal de Sódio Disparado por Voltagem NAV1.4/química , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Canal de Sódio Disparado por Voltagem NAV1.4/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/química , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Peptídeos/genética , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Distribuição Aleatória , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Venenos de Escorpião/genética , Venenos de Escorpião/farmacologia , Venenos de Escorpião/uso terapêutico , Escorpiões , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagem , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico
10.
Small ; 13(48)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29140604

RESUMO

Geometric and mechanical characterizations of hydrogel materials at the microscale are attracting increasing attention due to their importance in tissue engineering, regenerative medicine, and drug delivery applications. Contemporary approaches for measuring the these properties of hydrogel microbeads suffer from low-throughput, complex system configuration, and measurement inaccuracy. In this work, a continuous-flow device is developed to measure geometric and viscoelastic properties of hydrogel microbeads by flowing the microbeads through a tapered microchannel with an array of interdigitated microelectrodes patterned underneath the channel. The viscoelastic properties are derived from the trajectories of microbeads using a quasi-linear viscoelastic model. The measurement is independent of the applied volumetric flow rate. The results show that the geometric and viscoelastic properties of Ca-alginate hydrogel microbeads can be determined independently and simultaneously. The bulky high-speed optical systems are eliminated, simplifying the system configuration and making it a truly miniaturized device. A throughput of up to 394 microbeads min-1 is achieved. This study may provide a powerful tool for mechanical profiling of hydrogel microbeads to support their wide applications.

11.
Appl Opt ; 56(9): 2455-2461, 2017 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-28375354

RESUMO

A novel optical antenna with an off-axis confocal parabolic rotating surfaces configuration is designed for achieving maximum transmission efficiency. An improved 3-D ray tracing method based on the vector theory of reflection is used to simulate spatial rays transmitting through the antenna system. Aberrations and the spatial divergence angles of the output beam, which are caused by on-axial defocusing and off-axial defocusing between the primary reflector and secondary reflector, are visualized and effects on receiver efficiency of the antenna system are analyzed in detail. This work will provide a reference for improving the transmission efficiency of long-range communication systems.

12.
bioRxiv ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38746212

RESUMO

The Mediator complex, composed of about 30 conserved subunits, plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising Med12, Med13, CDK8, and CycC (Cyclin C), serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in Drosophila have revealed distinct phenotypes of CDK8-CycC and Med12-Med13 mutations, yet the underlying mechanism has remained unknown. Here, using Drosophila as a model organism, we show that depleting CDK8-CycC enhances E2F1 target gene expression and promotes cell-cycle progression. Conversely, depletion of Med12-Med13 affects the expression of ribosomal protein genes and fibrillarin, indicating a more severe reduction in ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Moreover, we found that the stability of CDK8 and CycC relies on Med12 and Med13, with a mutually interdependent relationship between Med12 and Med13. Furthermore, CycC stability depends on the other three CKM subunits. These findings reveal distinct roles for CKM subunits in vivo , with Med12-Med13 disruption exerting a more pronounced impact on ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Significance: The CDK8 kinase module (CKM), comprising CDK8, CycC, Med12, and Med13, is essential in the Mediator complex for RNA polymerase II-dependent transcription in eukaryotes. While expected to function jointly, CKM subunit mutations result in distinct phenotypes in Drosophila . This study investigates the mechanisms driving these differing effects. Our analysis reveals the role of Med12-Med13 pair in regulating ribosomal biogenesis and cellular growth, contrasting with the involvement of CDK8-CycC in E2F1-dependent cell-cycle progression. Additionally, an asymmetric interdependence in the stability of CDK8-CycC and Med12-Med13 was observed. CKM mutations or overexpression are associated with cancers and cardiovascular diseases. Our findings underscore the distinct impacts of CKM mutations on cellular growth and proliferation, advancing our understanding of their diverse consequences in vivo .

13.
Front Endocrinol (Lausanne) ; 15: 1284152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501103

RESUMO

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Esofágicas , Neoplasias Hepáticas , Neoplasias Pulmonares , Melanoma , Neoplasias Gástricas , Humanos , Glucose , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Linfócitos/patologia , Neoplasias Hepáticas/patologia , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia
14.
Biomolecules ; 13(7)2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37509104

RESUMO

The circadian clock adapts to the light-dark cycle and autonomously generates physiological and metabolic rhythmicity. Its activity depends on the central suprachiasmatic pacemaker. However, it also has an independent function in peripheral tissues such as the liver, adipose tissue, and skin, which integrate environmental signals and energy homeostasis. Hair follicles (HFs) maintain homeostasis through the HF cycle, which depends heavily on HF stem cell self-renewal and the related metabolic reprogramming. Studies have shown that circadian clock dysregulation in HFs perturbs cell cycle progression. Moreover, there is increasing evidence that the circadian clock exerts a significant influence on glucose metabolism, feeding/fasting, stem cell differentiation, and senescence. This suggests that circadian metabolic crosstalk plays an essential role in regulating HF regeneration. An improved understanding of the role of the circadian clock in HFs may facilitate the discovery of new drug targets for hair loss. Therefore, the present review provides a discussion of the relationship between the circadian clock and HF regeneration, mainly from the perspective of HF metabolism, and summarizes the current understanding of the mechanisms by which HFs function.


Assuntos
Relógios Circadianos , Ritmo Circadiano/fisiologia , Folículo Piloso , Pele , Jejum
15.
Curr Eye Res ; 48(12): 1112-1121, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37669915

RESUMO

PURPOSE: Loss of corneal transparency is one of the major causes of visual loss, generating a considerable health and economic burden globally. Corneal transplantation is the leading treatment procedure, where the diseased cornea is replaced by donated corneal tissue. Despite the rise of cornea donations in the past decade, there is still a huge gap between cornea supply and demand worldwide. 3D bioprinting is an emerging technology that can be used to fabricate tissue equivalents that resemble the native tissue, which holds great potential for corneal tissue engineering application. This study evaluates the manufacturability of 3D bioprinted acellular corneal grafts using low-cost equipment and software, not necessarily designed for bioprinting applications. This approach allows access to 3D printed structures where commercial 3D bioprinters are cost prohibitive and not readily accessible to researchers and clinicians. METHODS: Two extrusion-based methods were used to 3D print acellular corneal stromal scaffolds with collagen, alginate, and alginate-gelatin composite bioinks from a digital corneal model. Compression testing was used to determine moduli. RESULTS: The printed model was visually transparent with tunable mechanical properties. The model had central radius of curvature of 7.4 mm, diameter of 13.2 mm, and central thickness of 0.4 mm. The compressive secant modulus of the material was 23.7 ± 1.7 kPa at 20% strain. 3D printing into a concave mold had reliability advantages over printing into a convex mold. CONCLUSIONS: The printed corneal models exhibited visible transparency and a dome shape, demonstrating the potential of this process for the preparation of acellular partial thickness corneal replacements. The modified printing process presented a low-cost option for corneal bioprinting.


Assuntos
Bioimpressão , Humanos , Bioimpressão/métodos , Estudos de Viabilidade , Reprodutibilidade dos Testes , Substância Própria/cirurgia , Engenharia Tecidual/métodos , Alginatos , Alicerces Teciduais/química , Hidrogéis/química
16.
Clin Nutr ; 42(10): 1932-1939, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37634307

RESUMO

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Prognóstico , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
17.
Stem Cell Rev Rep ; 19(2): 443-454, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35962175

RESUMO

Stem cell senescence and depletion are major causes of aging and aging-related diseases. The NAD (Nicotinamide adenine dinucleotide) - SIRT1 (Silent Information Regulator 1) - PARP1 (Poly (ADP-ribose) polymerase-1) axis has gained interest owing to its significant role in regulating stem cell senescence and organismal aging. A recent study from our lab showed that pre-B-cell leukemia transcription factor1 (PBX1) overexpression attenuates hair follicle-derived mesenchymal stem cells (HF-MSCs) senescence and apoptosis by regulating ROS-mediated DNA damage via PARP1 downregulation; thus, suggesting that PARP1 downregulation is a common manifestation of the roles of both PBX1 and SIRT1 in HF-MSCs senescence attenuation, and implying a potential link between PBX1 and SIRT1. To this end, HF-MSCs overexpressing PBX1, overexpressing both PBX1 and PARP1, downregulating SIRT1, and overexpressing PBX1 as well as downregulating SIRT1 were generated, and senescence, apoptosis, DNA damage, and repair biomarkers were analyzed. Our results showed that (1) PBX1 overexpression alleviated HF-MSCs senescence and apoptosis accompanied by SIRT1 upregulation, PARP1 downregulation, and increased intracellular NAD and ATP levels. (2) SIRT1 knockdown enhanced cellular senescence and apoptosis, accompanied by increased ROS accumulation, DNA damage aggravation, and decreased intracellular NAD and ATP levels. (3) PBX1 overexpression rescued HF-MSCs senescence and apoptosis induced by SIRT1 knockdown. (4) PBX1 rescued PARP1 overexpression-mediated ATP and NAD depletion, accompanied by increased SIRT1 expression. Collectively, our results revealed that a positive interaction feedback loop exists between PBX1 and SIRT1. To the best of our knowledge we are the first to report that there is a PBX1-SIRT1-PARP1 axis that plays a critical role in alleviating HF-MSCs senescence and apoptosis. We provide a new perspective on the mechanisms underlying stem cell senescence as well as age-related disease prevention and treatment.


Assuntos
Transdução de Sinais , Sirtuína 1 , Espécies Reativas de Oxigênio , Sirtuína 1/genética , Sirtuína 1/metabolismo , NAD/metabolismo , Retroalimentação , Apoptose/genética , Trifosfato de Adenosina
18.
Toxics ; 11(2)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36851019

RESUMO

Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.

19.
J Colloid Interface Sci ; 612: 35-42, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-34974256

RESUMO

The development of an environmental-friendly thermal insulation and flame retardant material has attracted widespread attention in modern architecture. In this work, a kind of novel aerogel composites were prepared by incorporation of Mg(OH)2 coated hollow glass microspheres (HGM) into chitosan (CSA) matrix and then cross-linking by glutaraldehyde (abbreviated as CSA-HGM-Mg(OH)2). The as-prepared composite aerogel exhibits vertical directional channel with high porosity and excellent thermal insulation with a low thermal conductivity of 0.035 W m-1 k-1. Besides, it shows excellent flame retardancy with a high limit oxygen index (LOI) value up to 50.8, which is one of the highest values among the most of flame retardants reported previously. Also, a very low peak heat release rate (pHRR) of 24.12 kW m-2 was obtained which makes the aerogel composite reaching UL-94 V-0 rating. Such results may be attributed to a synergy effect by combination of its abundantly porous structure derived from HGM to give a better thermal insulation and excellent nonflammability of CSA and Mg(OH)2 to offer a superior flame retardancy. Taking advantages of its high mechanical strength, low cost materials, simple and scalable preparation method, CSA-HGM-Mg(OH)2 aerogel composites may hold great potential for future thermal insulation and flame retardant applications.

20.
Medicine (Baltimore) ; 101(6): e28859, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35147133

RESUMO

BACKGROUND: Myopia are common health problems that people experience in daily life. Pediatric myopia has become a major international public health concern that has a negative impact on physical, mental health of patients, and quality of life. Currently, there is no cure available. Press needle as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of press needle patching on early myopia. There is also a lack of systematic evaluation and analysis of acupoints and thumbtack needle. METHODS: We will electronically search Medline, Embase, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan-Fang Database from their inception to October 2021. In addition, we will manually retrieve other resources including the reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to press needle for the treatment of early myopia will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using afixed effect model or random effect model depend on the heterogeneity test. The total effective rate was the primary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted. Data synthesis will use the risk ratio and the standardized or weighted average difference of continuous data to represent the results. RESULTS: This study will analyze the clinical effective rate, pesudomyopia outcomes, quality of life, improvement of clinical symptoms of pesudomyopia, and validity of thumbtack needle for patients with pesudomyopia. CONCLUSION: This systematic review will provide evidence to judge whether thumbtack needle is an effective intervention for patients with early myopia. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021243151.


Assuntos
Terapia por Acupuntura , Miopia/terapia , Criança , Humanos , Metanálise como Assunto , Qualidade de Vida , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
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