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1.
PLoS Genet ; 19(8): e1010869, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37556491

RESUMO

Metabolic pathways are known to sense the environmental stimuli and result in physiological adjustments. The responding processes need to be tightly controlled. Here, we show that upon encountering P. aeruginosa, C. elegans upregulate the transcription factor ets-4, but this upregulation is attenuated by the ribonuclease, rege-1. As such, mutants with defective REGE-1 ribonuclease activity undergo ets-4-dependent early death upon challenge with P. aeruginosa. Furthermore, mRNA-seq analysis revealed associated global changes in two key metabolic pathways, the IIS (insulin/IGF signaling) and TOR (target of rapamycin) kinase signaling pathways. In particular, failure to degrade ets-4 mRNA in activity-defective rege-1 mutants resulted in upregulation of class II longevity genes, which are suppressed during longevity, and activation of TORC1 kinase signaling pathway. Genetic inhibition of either pathway way was sufficient to abolish the poor survival phenotype in rege-1 worms. Further analysis of ETS-4 ChIP data from ENCODE and characterization of one upregulated class II gene, ins-7, support that the Class II genes are activated by ETS-4. Interestingly, deleting an upregulated Class II gene, acox-1.5, a peroxisome ß-oxidation enzyme, largely rescues the fat lost phenotype and survival difference between rege-1 mutants and wild-types. Thus, rege-1 appears to be crucial for animal survival due to its tight regulation of physiological responses to environmental stimuli. This function is reminiscent of its mammalian ortholog, Regnase-1, which modulates the intestinal mTORC1 signaling pathway.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Transdução de Sinais/genética , Insulina/genética , Insulina/metabolismo , Ribonucleases/genética , Ribonucleases/metabolismo , RNA Mensageiro/metabolismo , Mamíferos/genética
2.
Curr Issues Mol Biol ; 46(6): 6267-6283, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38921045

RESUMO

Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251-262 and ApoA-I70-83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251-262 HNE, IgM anti-ApoA-I70-83 HNE, IgG anti-ApoA-I251-262, IgG anti-ApoA-I70-83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251-262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251-262 HNE may increase the severity of CAD at high and low levels, respectively.

3.
Opt Express ; 32(11): 20024-20034, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859121

RESUMO

An optical fiber sensing probe using a composite sensitive film of polyacrylonitrile (PAN) nanofiber membrane and gold nanomembrane is presented for the detection of a carcinoembryonic antigen (CEA), a biomarker associated with colorectal cancer and other diseases. The probe is based on a tilted fiber Bragg grating (TFBG) with a surface plasmon resonance (SPR) gold nanomembrane and a functionalized polyacrylonitrile (PAN) PAN nanofiber coating that selectively binds to CEA molecules. The performance of the probe is evaluated by measuring the spectral shift of the TFBG resonances as a function of CEA concentration in buffer. The probe exhibits a sensitivity of 0.46 dB/(µg/ml), a low limit of detection of 505.4 ng/mL in buffer, and a good selectivity and reproducibility. The proposed probe offers a simple, cost-effective, and a novel method for CEA detection that can be potentially applied for clinical diagnosis and monitoring of CEA-related diseases.


Assuntos
Resinas Acrílicas , Antígeno Carcinoembrionário , Ouro , Nanofibras , Fibras Ópticas , Ressonância de Plasmônio de Superfície , Antígeno Carcinoembrionário/análise , Ouro/química , Nanofibras/química , Ressonância de Plasmônio de Superfície/instrumentação , Ressonância de Plasmônio de Superfície/métodos , Resinas Acrílicas/química , Humanos , Técnicas Biossensoriais/instrumentação , Membranas Artificiais , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Tecnologia de Fibra Óptica/instrumentação
4.
Opt Express ; 32(7): 12656-12666, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571083

RESUMO

Ghost imaging (GI) requires each echo from the object being correctly matched with the corresponding illuminiation pattern. We proposed a way for such matching with no physical synchronization towards bistatic configuration. The illumination is dually encoded in spatial and time domain. With aperiodic waveform and progressive correlation, the echoes can be correctly located and images can be obtained. In the experiments, our scheme is verified under different levels of signal to noise ratios, as well as different intensity of crosstalk. Ghost imaging with two transmitters and one receiver is also demonstrated. With our method, it is also possible to improve the imaging speed with multiple sources.

5.
Cardiovasc Diabetol ; 23(1): 139, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664790

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions. METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.


Assuntos
Cardiomiopatias Diabéticas , Análise de Célula Única , Transcriptoma , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Animais , Perfilação da Expressão Gênica , Cromatina/metabolismo , Cromatina/genética , Camundongos Endogâmicos C57BL , Redes Reguladoras de Genes , Montagem e Desmontagem da Cromatina , Modelos Animais de Doenças , Masculino , RNA-Seq , Regulação da Expressão Gênica , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/patologia
6.
J Pharmacol Sci ; 155(3): 101-112, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797534

RESUMO

Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1ß, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.


Assuntos
Acetofenonas , Disfunção Cognitiva , Pneumopatias , Pneumopatias/complicações , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Macrófagos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Masculino , Animais , Camundongos , Fator de Necrose Tumoral alfa , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , MicroRNAs/sangue , MicroRNAs/genética , Espécies Reativas de Oxigênio/metabolismo
7.
Int J Audiol ; : 1-10, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251843

RESUMO

OBJECTIVE: Approximately 30-50% of sudden sensorineural hearing loss (SSNHL) patients show poor response to systemic steroid therapy. Additionally, the most appropriate treatment for patients with refractory sudden sensorineural hearing loss (RSSNHL) is unknown. This study aimed to explore the best treatment for RSSNHL. DESIGN: Using a frequentist contrast-based model and PRISMA guidelines, this study compared five salvage regimes: intratympanic injection of steroids (ITS), hyperbaric oxygen (HBO) therapy, post auricle steroid injection (PSI), ITS combined with HBO therapy, and continued systemic steroids. STUDY SAMPLE: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomised controlled trials and cohort studies comparing treatment regimens for RSSNHL. RESULTS: Compared with the control group (no additional treatment), PSI and ITS demonstrated significant improvements. The mean hearing gain was greater after PSI (11.1 dB [95% CI, 4.4-17.9]) than after ITS (7.7 dB [95% CI, 4.8-10.7]). When a restricted definition of RSSNHL was used, the ITS + HBO therapy showed the largest difference in improvement for pure tone average compared with the control group (14.5 dB [95% CI, 4.2-25.0]). CONCLUSIONS: The administration of either PSI or ITS leads to the greatest therapeutic effect in patients with RSSNHL. However, a consensus on the definition of RSSNHL is needed.

8.
Environ Toxicol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884142

RESUMO

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

9.
Sensors (Basel) ; 24(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38610476

RESUMO

The advancement of unmanned aerial vehicles (UAVs) enables early detection of numerous disasters. Efforts have been made to automate the monitoring of data from UAVs, with machine learning methods recently attracting significant interest. These solutions often face challenges with high computational costs and energy usage. Conventionally, data from UAVs are processed using cloud computing, where they are sent to the cloud for analysis. However, this method might not meet the real-time needs of disaster relief scenarios. In contrast, edge computing provides real-time processing at the site but still struggles with computational and energy efficiency issues. To overcome these obstacles and enhance resource utilization, this paper presents a convolutional neural network (CNN) model with an early exit mechanism designed for fire detection in UAVs. This model is implemented using TSMC 40 nm CMOS technology, which aids in hardware acceleration. Notably, the neural network has a modest parameter count of 11.2 k. In the hardware computation part, the CNN circuit completes fire detection in approximately 230,000 cycles. Power-gating techniques are also used to turn off inactive memory, contributing to reduced power consumption. The experimental results show that this neural network reaches a maximum accuracy of 81.49% in the hardware implementation stage. After automatic layout and routing, the CNN hardware accelerator can operate at 300 MHz, consuming 117 mW of power.

10.
J Med Ultrasound ; 32(2): 116-120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882614

RESUMO

Nonalcoholic fatty liver disease (NAFLD), among the most common chronic liver diseases worldwide, affects approximately 25% of the global population. Its incidence is increasing owing to various risk factors, including genetic variation, metabolic health, dietary habits, and microbiota. Hepatic steatosis is a critical histological characteristic of NAFLD. Evaluating liver fat content is vital for identifying and following up with patients at risk of developing NAFLD. NAFLD includes simple liver steatosis and more severe forms such as inflammation, nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The early assessment of fatty liver is important for reversing liver disease progression. Metabolic (dysfunction)-associated fatty liver disease recently replaced NAFLD as the most common hepatic disease worldwide. This article reviews the current state of noninvasive imaging, especially ultrasound, for liver fat quantification.

11.
Am J Physiol Cell Physiol ; 324(2): C222-C235, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36622073

RESUMO

This study investigates the mechanism by which microRNA (miR)-30e-3p reduces coronary microembolism (CME)-induced cardiomyocyte pyroptosis and inflammation. Cardiac function tests, histological staining, and transmission electron microscopy were performed on CME-model rats injected with adeno-associated viral vectors. Cardiomyocytes were transfected 24 h before a cellular model of pyroptosis was established via treatment with 1 µg/mL lipopolysaccharide (LPS) for 4 h and 5 mM ATP for 30 min. Pyroptosis, inflammation, and Wnt/ß-catenin signaling in cardiomyocytes were detected. Dual-luciferase reporter assays and/or RNA pull-down assays were performed to verify the binding of miR-30e-3p to HDAC2 mRNA or HDAC2 to the SMAD7 promoter. Chromatin immunoprecipitation was used to assess the level of H3K27 acetylation at the SMAD7 promoter. miR-30e-3p and SMAD7 expression levels were downregulated and HDAC2 expression was upregulated with CME. The overexpression of miR-30e-3p restored cardiac functions in CME-model rats and reduced serum cTnI, IL-18, and IL-1ß levels, microinfarcts, inflammatory cell infiltration, apoptosis, collagen content, and GSDMD-N, cleaved caspase-1, and NLRP3 expression in the myocardium, but these effects were reversed by SMAD7 knockdown. The overexpression of miR-30e-3p or knockdown of HDAC2 reduced LDH, IL-18, and IL-1ß secretion, propidium iodide intake, and GSDMD-N, NLRP3, cleaved caspase-1, Wnt3a, Wnt5a, and ß-catenin expression in the cardiomyocyte model. miR-30e-3p inhibited the expression of HDAC2 by binding HDAC2 mRNA. HDAC2 repressed the expression of SMAD7 by catalyzing H3K27 deacetylation at the SMAD7 promoter. miR-30e-3p, by binding HDAC2 to promote SMAD7 expression, reduces CME-induced cardiomyocyte pyroptosis and inflammation.


Assuntos
MicroRNAs , Miócitos Cardíacos , Ratos , Animais , Miócitos Cardíacos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Interleucina-18/metabolismo , beta Catenina/metabolismo , Piroptose/genética , Inflamação , RNA Mensageiro , Caspases/metabolismo , Proteína Smad7/genética , Proteína Smad7/metabolismo , Histona Desacetilase 2/genética
12.
J Biol Chem ; 298(11): 102525, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36162509

RESUMO

RNA N6-methyladenosine (m6A) is the most abundant internal mRNA modification and forms part of an epitranscriptomic system that modulates RNA function. m6A is reversibly catalyzed by specific enzymes, and those modifications can be recognized by RNA-binding proteins that in turn regulate biological processes. Although there are many reports demonstrating m6A participation in critical biological functions, this exploration has mainly been conducted through the global KO or knockdown of the writers, erasers, or readers of m6A. Consequently, there is a lack of information about the role of m6A on single transcripts in biological processes, posing a challenge in understanding the biological functions of m6A. Here, we demonstrate a CRISPR/dCas13a-based RNA m6A editors, which can target RNAs using a single or multiple CRISPR RNA array to methylate or demethylate m6A in human 293T cells and mouse embryonic stem cells. We systematically assay its capabilities to enable the targeted rewriting of m6A dynamics, including modulation of circular RNA translation and transcript half-life. Finally, we use the system to specifically modulate m6A levels on the noncoding XIST (X-inactive specific transcript) to modulate X chromosome silencing and activation. The editors described here can be used to explore the roles of m6A in biological processes.


Assuntos
Adenosina , RNA Longo não Codificante , RNA , Animais , Humanos , Camundongos , Adenosina/metabolismo , Regulação da Expressão Gênica , RNA/genética , RNA/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Sistemas CRISPR-Cas , Células HEK293 , Células-Tronco Embrionárias Murinas , RNA Circular/genética
13.
Oncologist ; 28(7): e575-e584, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930304

RESUMO

BACKGROUND: Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). More effective treatment options are highly awaited. The aim of this study was to evaluate the toxicity and feasibility of gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy on a 21-day cycle in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore preliminary efficacy. METHODS: Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 in a 3+3 dose escalation design. According to patients` body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25-1.5 m2 received S-1 40 mg/day initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/day initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy, including best objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). adverse events (AEs) were evaluated according to the NCI-CTCAE 5.0. Tumor response was assessed using the RECIST 1.1. RESULTS: A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25-1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/day (body surface area: >1.5 m2) was considered to be the MTD in GAS chemotherapy on a 21-day cycle. No grade 4 AEs or treatment-related deaths were observed. The most commonly occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). Response assessment showed that the best ORR was 36.8% (7 of 19 patients) and the DCR was 94.7% (18 of 19 patients). The median PFS was 5.3 (95% CI, 4.6 to 6.0) months and the median OS was 10.3 (95% CI, 8.1 to 12.5) months. CONCLUSION: GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/day (body surface area: >1.5 m2) was found to have acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. We conclude that further trials with this combination are warranted. (Trial Identifier: ChiCTR1900027833 [chictr.org]).


Assuntos
Adenocarcinoma , Gencitabina , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Paclitaxel , Adenocarcinoma/patologia , Neoplasias Pancreáticas
14.
Mol Carcinog ; 62(7): 951-962, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37014154

RESUMO

Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo. We performed SPRY2 immunohistochemical staining in 143 CRC specimens and analyzed the staining results with various clinicopathological characteristics in relation to KRAS mutation status. SPRY2 knockdown in Caco-2 cells carrying the wild-type (WT) KRAS gene upregulated phosphorylated ERK (p-ERK) levels and increased cell proliferation in vitro, but inhibited cell invasion. However, SPRY2 knockdown in SW480 cells (activating KRAS mutant) or Caco-2 cells transfected with KRAS-mutant plasmid did not significantly alter p-ERK levels, cell proliferation, or invasion. The xenografts of SPRY2-knockdown Caco-2 cells were larger with less deep muscle invasion than those of control cells. The clinical cohort study revealed a positive association of SPRY2 protein expression with pT status, lymphovascular invasion, and perineural invasion in KRAS-WT CRCs. However, the associations were not observed in KRAS-mutant CRCs. Interestingly, high SPRY2 expression was related to shorter cancer-specific survival in both KRAS-WT and KRAS-mutant CRC patients. Our study demonstrated the dual role of SPRY2 as an inhibitor of RAS/ERK-driven proliferation and as a promoter of cancer invasion in KRAS-WT CRC. SPRY2 may promote the invasion and progression of KRAS-WT CRC, and might also enhance KRAS-mutant CRC progression through pathways other than invasion.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Células CACO-2 , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Neoplasias Colorretais/patologia , Proliferação de Células , Mutação , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
15.
Chaos ; 33(1): 011101, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36725633

RESUMO

Critical physical systems with large numbers of molecules can show universal and scaling behaviors. It is of interest to know whether human societies with large numbers of people can show the same behaviors. Here, we use network theory to analyze Chinese history in periods 209 BCE-23 CE and 515-618 CE) related to the Western Han-Xin Dynasty and the late Northern Wei-Sui Dynasty, respectively. Two persons are connected when they appear in the same historical event. We find that the historical networks from two periods separated about 500 years have interesting universal and scaling behaviors, and they are small-world networks; their average cluster coefficients as a function of degree are similar to the network of movie stars. In the historical networks, the persons with larger degrees prefer to connect with persons with a small degree; however, in the network of movie stars, the persons with larger degrees prefer to connect with persons with large degrees. We also find an interesting similar mechanism for the decline or collapse of historical Chinese dynasties. The collapses of the Xin dynasty (9-23 CE) and the Sui dynasty (581-618 CE) were initiated from their arrogant attitude toward neighboring states.

16.
J Formos Med Assoc ; 122(10): 1042-1049, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37019722

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on healthcare system and patients. This study aimed to evaluate the effect of the COVID-19 pandemic on the perceptions of patients with inflammatory bowel disease (IBD). METHODS: This prospective multicenter study was conducted between July 2021 and December 2021. Patients with IBD answered a structured questionnaire, and their degree of anxiety was assessed using a visual analogue scale (VAS) before and after reading educational materials. RESULTS: A total of 225 (47.67%) patients with Crohn's disease, 244 (51.69%) with ulcerative colitis and 3 (0.64%) with indeterminate colitis were enrolled. Common concerns were adverse events from vaccination (20.34%), and higher risks of developing severe COVID-19 (19.28%) and COVID-19 infection (16.31%) than the general population. Medications deemed by the patients to increase the risk of COVID-19 were immunomodulators (16.10%), anti-tumor necrosis factor-α antagonists (9.96%), and corticosteroids (9.32%). Thirty-five (7.42%) patients self-discontinued IBD medication, of whom 12 (34.28%) had worse symptoms. Older age (>50 years) (OR 1.10, 95% CI 1.01-1.19, p = 0.03), IBD-related complications (OR 1.16, 95% CI 1.04-1.28, p = 0.01), education status below senior high school (OR 1.22, 95% CI 1.08-1.37, p = 0.001), and residing in north-central Taiwan (OR 1.21, 95% CI 1.10-1.34, p < 0.001) were associated with more anxiety. None of the enrolled patients contracted COVID-19. The anxiety VAS score (mean ± SD) improved after reading the educational materials (3.84 ± 2.33 vs. 2.81 ± 1.96, p < 0.001). CONCLUSION: The medical behavior of IBD patients was influenced by the COVID-19 pandemic, and their anxiety could be mitigated after education.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Prospectivos , Taiwan/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia
17.
Chin J Physiol ; 66(6): 485-493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149561

RESUMO

Acute body mass loss before competitions in combat sports usually leads to loss in fat-free mass. Beta-hydroxy-beta-methylbutyrate (HMB) has been shown to increase skeletal muscle mass and muscle strength in various muscle wasting conditions. This study investigated the effect of HMB supplementation on body composition and sport-specific performance in well-trained boxers consuming a hypocaloric diet. Twelve male college boxers were divided into the HMB and placebo (PLA) groups using a body weight-matched single-blind parallel design. The study comprised a 6-day weight loss period (days 1-6), followed by a 3-day competition period (days 7-9). The participants in both the groups consumed 16 kcal/kg/day, including 1.6-1.7 g/kg of carbohydrates, 1.2-1.3 g/kg of protein, and 0.45-0.5 g/kg of fat during the 9-day period. The HMB group consumed 3 g/day HMB. Body composition measurement, isometric mid-thigh pull (IMTP), and a simulated boxing match were performed at baseline and on days 7, 8, and 9. Fasting blood samples were collected on the day before day 1 and on days 7, 8, and 9. Body mass was significantly decreased after the 6-day weight loss period (HMB group: baseline: 69.4 ± 11.2 kg, day 7: 67.1 ± 11.2 kg; PLA group: baseline: 68.6 ± 12.1 kg, day 7: 65.7 ± 11.5 kg, P < 0.05) while it was unchanged on the 3-day competition period in both the groups. Fat-free mass in the HMB group was maintained throughout the 9-day period (baseline: 56.7 ± 9.3 kg, day 7: 56.3 ± 8.7 kg, day 9: 55.8 ± 9.5 kg) whereas it significantly decreased on days 7 and 9 compared to the baseline in the PLA group (baseline: 55.2 ± 6.4 kg, day 7: 54.1 ± 6.6 kg, day 9: 54.0 ± 6.6 kg, P < 0.05). In the PLA group, the average and maximal heart rates in round 1 and the average heart rate in round 2 on days 8 and 9 were significantly lower than those at baseline, while these parameters were unchanged in the HMB group. The maximal force and the rate of force development in the IMTP remained unchanged among the different timepoints in both the groups. The blood biochemical parameters were similar at any timepoint between the PLA and HMB groups. HMB supplementation during acute weight loss may preserve fat-free mass and maintain heart rate response in subsequent simulated matches in well-trained boxers. In addition, HMB supplementation had a nonsignificant effect on glucose, fat, and protein metabolism during energy restriction.


Assuntos
Dieta Redutora , Suplementos Nutricionais , Humanos , Masculino , Composição Corporal , Músculo Esquelético/fisiologia , Obesidade , Poliésteres/farmacologia , Método Simples-Cego , Redução de Peso
18.
J Prosthet Dent ; 129(5): 676-680, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-34489088

RESUMO

A 21-year-old woman with multiple congenitally missing maxillary anterior teeth received interdisciplinary treatment to restore function and esthetics. The treatment was initiated with orthodontic treatment, followed by implant placement, bone and soft-tissue augmentation, and prosthetic treatment including a screw-retained implant-supported 2-unit cantilever fixed dental prosthesis.


Assuntos
Anodontia , Implantes Dentários , Feminino , Humanos , Adulto Jovem , Adulto , Anodontia/cirurgia , Prótese Dentária Fixada por Implante , Estética Dentária , Parafusos Ósseos
19.
Environ Geochem Health ; 45(8): 5813-5827, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37148428

RESUMO

In this research, enrichment factor (EF) and pollution load index were utilized to explore the contamination characteristics of toxic elements (TEs) in park dust. The results exhibited that park dust in the study area was mainly moderately polluted, and the EF values of dust Cd, Zn, Pb, Cu and Sb were all > 1. The concentrations of Cr, Cu, Zn and Pb increased with the decrease of dust particle size. The investigation results of chemical speciation and bioavailability of TEs showed that Zn had the highest bioavailability. Three sources of TEs were determined by positive matrix factorization model, Pearson correlation analysis and geostatistical analysis, comprising factor 1 mixed sources of industrial and transportation activities (46.62%), factor 2 natural source (25.56%) and factor 3 mixed source of agricultural activities and the aging of park infrastructures (27.82%). Potential ecological risk (PER) and human health risk (HHR) models based on source apportionment were exploited to estimate PER and HHR of TEs from different sources. The mean PER value of TEs in the park dust was 114, indicating that ecological risk in the study area was relatively high. Factor 1 contributed the most to PER, and the pollution of Cd was the most serious. There were no significant carcinogenic and non-carcinogenic risks for children and adults in the study area. And factor 3 was the biggest source of non-carcinogenic risk, and As, Cr and Pb were the chief contributor to non-carcinogenic risk. The primary source of carcinogenic risk was factor 2, and Cr was the cardinal cancer risk element.


Assuntos
Monitoramento Ambiental , Metais Pesados , Adulto , Criança , Humanos , Monitoramento Ambiental/métodos , Poeira/análise , Cádmio/toxicidade , Cádmio/análise , Chumbo/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Medição de Risco/métodos , Carcinógenos/análise , China , Cidades
20.
J Exerc Sci Fit ; 21(1): 6-13, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36349303

RESUMO

Background: /Objective: In Taiwan, physical inactivity is highly prevalent among children and adolescents. Chinese Taipei (Taiwan) joined the Global Matrix 3.0 in 2018 to share local data on childhood physical activity and related factors with the international community. This study reports the grades for 10 indicators endorsed by the Global Matrix 4.0 and 1 additional indicator. Methods: Local data for school-aged children and adolescents (approximately 5-17 years old) from 2017 to 2022 were used to determine the grades. The data were obtained from online academic databases and websites of government agencies. The highest priority was given to national surveys, followed by studies using nationally representative samples. Results: The data revealed very poor Overall Physical Activity, Organized Sport Participation, and Active Play (F, D-, and F, respectively). Active Transportation, Sedentary Behavior, and Family and Peers were also below average (C-, D+, and D-, respectively). Taiwan's central and local governments have recognized the importance of physical activity by implementing related policy and improving public sports facilities. Accordingly, School and Community and the Built Environment both received a grade of A-, and Government Strategies and Investments received a B+. Physical Fitness received an INC for lack of data. An additional indicator, body mass index, received a grade of B-. Conclusions: Despite great effort by governments and schools, physical activity levels are low and sedentary behavior is prevalent among Taiwanese children and adolescents.

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