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1.
Biomed Pharmacother ; 176: 116935, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38876050

RESUMEN

Breast cancer is one of the most common malignant tumors in women and is a serious threat to women's health. The pentose phosphate pathway (PPP) is a mode of oxidative breakdown of glucose that can be divided into oxidative (oxPPP) and non-oxidative (non-oxPPP) stages and is necessary for cell and body survival. However, abnormal activation of PPP often leads to proliferation, migration, invasion, and chemotherapy resistance in breast cancer. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in PPP oxidation. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) produced by G6PD is the raw material for cholesterol and lipid synthesis and can resist the production of oxygen species (ROS) and reduce oxidative stress damage to tumor cells. Transketolase (TKT) is a key enzyme in non-oxPPP. Ribose 5-phosphate (R5P), produced by TKT, is a raw material for DNA and RNA synthesis, and is essential for tumor cell proliferation and DNA damage repair. In this review, we describe the role and specific mechanism of the PPP and the two most important enzymes of the PPP, G6PD and TKT, in the malignant progression of breast cancer, providing strategies for future clinical treatment of breast cancer and a theoretical basis for breast cancer research.


Asunto(s)
Neoplasias de la Mama , Progresión de la Enfermedad , Glucosafosfato Deshidrogenasa , Vía de Pentosa Fosfato , Transcetolasa , Transcetolasa/metabolismo , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , Vía de Pentosa Fosfato/efectos de los fármacos , Animales
2.
Cyborg Bionic Syst ; 5: 0124, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846791

RESUMEN

The parameter setting of functional electrical stimulation (FES) is important for active recovery training since it affects muscle health. Among the FES parameters, current amplitude is the most influential factor. To explore the FES effect on the maximum stimulation time, this study establishes a curve between FES current amplitude and the maximum stimulation time based on muscle fatigue. We collect 10 subjects' surface electromyography under dumbbell weightlifting training and analyze the muscle fatigue state by calculating the root mean square (RMS) of power. By analyzing signal RMS, the fatigue characteristic curves under different fatigue levels are obtained. According to the muscle response under FES, the relationship curve between the current amplitude and the maximum stimulation time is established and FES parameters' effect on the maximum stimulation time is obtained. The linear curve provides a reference for FES parameter setting, which can help to set stimulation time safely, thus preventing the muscles from entering an excessive fatigue state and becoming more active to muscle recovery training.

3.
Mol Biol Evol ; 41(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38829799

RESUMEN

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.


Asunto(s)
Aclimatación , Frío , Animales , Ratas , Aclimatación/genética , China , Fenotipo , Variación Genética , Adaptación Fisiológica/genética , Regulación de la Temperatura Corporal/genética , Cambio Climático
4.
Sci Total Environ ; 944: 173703, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-38852870

RESUMEN

Glacial changes are crucial to regional water resources and ecosystems in the Sawir Mountains. However, glacial changes, including the mass balance and glacial meltwater of the Sawir Mountains, have sparsely been reported. Three model calibration strategies were constructed including a regression model based on albedo and in-situ mass balance of Muz Taw Glacier (A-Ms), regression model based on albedo and geodetic mass balance of valley, cirque, and hanging glaciers (A-Mr), and degree-day model (DDM) to obtain a reliable glacier mass balance in the Sawir Mountains and provide the latest understanding in the contribution of glacial meltwater runoff to regional water resources. The results indicated that the glacial albedo reduction was significant from 2000 to 2020 for the entire Sawir Mountains, with a rate of 0.015 (10a)-1, and the spatial pattern was higher in the east compared to the west. Second, the three strategies all indicated that the glacier mass balance has been continuously negative during the past 20 periods, and the average annual glacier mass balance was -1.01 m w.e. Third, the average annual glacial meltwater runoff in the Sawir Mountains from 2000 to 2020 was 22 × 106 m3, and its contribution to streamflow was 25.81 % from 2000 to 2018. The glacier contribution rates in the Ulkun- Ulastu, Lhaster, and Kendall River basins were 31.37 %, 22.51 %, and 19.27 %, respectively.

5.
J Transl Med ; 22(1): 558, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862971

RESUMEN

PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription­quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Proliferación Celular , Neoplasias Colorrectales , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Regulación Neoplásica de la Expresión Génica , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Fluorodesoxiglucosa F18/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Femenino , Masculino , Línea Celular Tumoral , Persona de Mediana Edad , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Anciano
6.
Int J Biol Macromol ; : 133037, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897523

RESUMEN

With the development of renewable energy technologies, the demand for efficient energy storage systems is growing. Supercapacitors have attracted considerable attention as efficient electrical energy storage devices because of their excellent power density, fast charging and discharging capabilities, and long cycle life. Carbon nanofibers are widely used as electrode materials in supercapacitors because of their excellent mechanical properties, electrical conductivity, and light weight. Although environmental factors are increasingly driving the application of circular economy concepts in materials science, lignin is an underutilized but promising environmentally benign electrode material for supercapacitors. Lignin-based carbon nanofibers are ideal for preparing high-performance supercapacitor electrode materials owing to their unique chemical stability, abundance, and environmental friendliness. Electrospinning is a well-known technique for producing large quantities of uniform lignin-based nanofibers, and is the simplest method for the large-scale production of lignin-based carbon nanofibers with specific diameters. This paper reviews the latest research progress in the preparation of lignin-based carbon nanofibers using the electrospinning technology, discusses the prospects of their application in supercapacitors, and analyzes the current challenges and future development directions. This is expected to have an enlightening effect on subsequent research.

7.
Biochem Pharmacol ; : 116372, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38885773

RESUMEN

MicroRNA and mitofusin-2 (Mfn2) play an important role in the myocardial apoptosis induced by acute myocardial infarction (AMI). However, the target relationship and underlying mechanism associated with interorganelle interaction between endoplasmic reticulum (ER) and mitochondria under ischemic condition is not completely clear. MI-induced injury, Mfn2 expression, Mfn2-mediated mitochondrial function and ER stress, and target regulation by miRNA-15b (miR-15b) were evaluated by animal MI and cellular hypoxic models with advanced molecular techniques. The results confirmed that Mfn2 was down-regulated and miR-15b was up-regulated upon the target binding profile under ischemic/hypoxic condition. Our data showed that miR-15b caused cardiac apoptotic injury that was reversed by rAAV9-anti-miR-15b or AMO-15b. The damage effect of miR-15b on Mfn2 expression and mitochondrial function was observed and rescued by rAAV9-anti-miR-15b or AMO-15b. The targeted regulation of miR-15b on Mfn2 was verified by luciferase reporter and microRNA-masking. Importantly, miR-15b-mediated Mfn2 suppression activated PERK/CHOP pathway, by which leads to ER stress and mitochondrial dysfunction, and cardiac apoptosis eventually. In conclusion, our research, for the first time, revealed the missing molecular link in Mfn2 and apoptosis and elucidated that pro-apoptotic miR-15b plays crucial roles during the pathogenesis of AMI through down-regulation of Mfn2 and activation of PERK-mediated ER stress. These findings may provide an opportunity to develop new therapies for prophylaxis and treatment of ischemic heart disease.

8.
Clin Cardiol ; 47(6): e24305, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38884449

RESUMEN

BACKGROUND: The coronary artery disease-reporting and data system (CAD-RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results. Artificial intelligence software can quantify the plaque composition, fat attenuation index, and fractional flow reserve. OBJECTIVE: To analyze plaque features of varying severity in patients with a combination of CAD-RADS stenosis and plaque burden categorization and establish a random forest classification model. METHODS: The data of 100 patients treated between April 2021 and February 2022 were retrospectively collected. The most severe plaque observed in each patient was the target lesion. Patients were categorized into three groups according to CAD-RADS: CAD-RADS 1-2 + P0-2, CAD-RADS 3-4B + P0-2, and CAD-RADS 3-4B + P3-4. Differences and correlations between variables were assessed between groups. AUC, accuracy, precision, recall, and F1 score were used to evaluate the diagnostic performance. RESULTS: A total of 100 patients and 178 arteries were included. The differences of computed tomography fractional flow reserve (CT-FFR) (H = 23.921, p < 0.001), the volume of lipid component (H = 12.996, p = 0.002), the volume of fibro-lipid component (H = 8.692, p = 0.013), the proportion of lipid component volume (H = 22.038, p < 0.001), the proportion of fibro-lipid component volume (H = 11.731, p = 0.003), the proportion of calcification component volume (H = 11.049, p = 0.004), and plaque type (χ2 = 18.110, p = 0.001) was statistically significant. CONCLUSION: CT-FFR, volume and proportion of lipid and fibro-lipid components of plaques, the proportion of calcified components, and plaque type were valuable for CAD-RADS stenosis + plaque burden classification, especially CT-FFR, volume, and proportion of lipid and fibro-lipid components. The model built using the random forest was better than the clinical model (AUC: 0.874 vs. 0.647).


Asunto(s)
Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Vasos Coronarios , Reserva del Flujo Fraccional Miocárdico , Placa Aterosclerótica , Índice de Severidad de la Enfermedad , Humanos , Masculino , Femenino , Reserva del Flujo Fraccional Miocárdico/fisiología , Estudios Retrospectivos , Angiografía por Tomografía Computarizada/métodos , Persona de Mediana Edad , Angiografía Coronaria/métodos , Estenosis Coronaria/fisiopatología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/fisiopatología , Anciano
9.
Chem Res Toxicol ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38885202

RESUMEN

Chlortoluron (CTU) is an herbicide extensively used in agricultural settings for crop cultivation. Its presence in water has been identified as a pollutant detrimental to aquatic species. The objective of the present study was to explore the metabolic activation and hepatotoxicity of CTU. Through human and rat liver microsomal incubations supplemented with CTU, nicotinamide adenine dinucleotide phosphate (NADPH), and either glutathione or N-acetyl cysteine, a benzylic alcohol metabolite (M1) was discerned, alongside a phenol metabolite (M2), a glutathione conjugate (M3), and an N-acetyl cysteine conjugate (M4). In rats exposed to CTU, biliary M3 and urinary M4 were detected in their bile and urine, respectively. The generation of M1 was detected in the presence of NADPH. The observation of M3 and M4 suggests the formation of an iminoquinone methide intermediate arising from the oxidation of M1. CYP3A4 was found to be the principal enzyme catalyzing the metabolic activation of CTU. Furthermore, CTU exhibited cytotoxic properties in cultured rat primary hepatocytes in a concentration-dependent pattern. Concomitant treatment of hepatocytes with ketoconazole mitigated their susceptibility to the cytotoxic effects of CTU.

10.
Metabolomics ; 20(3): 52, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722414

RESUMEN

INTRODUCTION: Metabolite signatures for blood pressure (BP) may reveal biomarkers, elucidate pathogenesis, and provide prevention targets for high BP. Knowledge regarding metabolites associated with BP in adolescence remains limited. OBJECTIVES: Investigate the associations between metabolites and adolescent BP, both cross-sectionally (in early and late adolescence) and prospectively (from early to late adolescence). METHODS: Participants are from the Project Viva prospective cohort. During the early (median: 12.8 years; N = 556) and late (median: 17.4 years; N = 501) adolescence visits, we conducted untargeted plasma metabolomic profiling and measured systolic (SBP) and diastolic BP (DBP). We used linear regression to identify metabolites cross-sectionally associated with BP at each time point, and to assess prospective associations of changes in metabolite levels from early to late adolescence with late adolescence BP. We used Weighted Gene Correlation Network Analysis and Spearman's partial correlation to identify metabolite clusters associated with BP at each time point. RESULTS: In the linear models, higher androgenic steroid levels were consistently associated with higher SBP and DBP in early and late adolescence. A cluster of 59 metabolites, mainly composed of androgenic steroids, correlated with higher SBP and DBP in early adolescence. A cluster primarily composed of fatty acid lipids was marginally associated with higher SBP in females in late adolescence. Multiple metabolites, including those in the creatine and purine metabolism sub-pathways, were associated with higher SBP and DBP both cross-sectionally and prospectively. CONCLUSION: Our results shed light on the potential metabolic processes and pathophysiology underlying high BP in adolescents.


Asunto(s)
Presión Sanguínea , Metabolómica , Humanos , Adolescente , Presión Sanguínea/fisiología , Masculino , Femenino , Metabolómica/métodos , Estudios Transversales , Estudios Prospectivos , Niño , Biomarcadores/sangre , Estados Unidos , Metaboloma/fisiología , Estudios de Cohortes
11.
Chem Res Toxicol ; 37(6): 935-943, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38761382

RESUMEN

Amitriptyline (ATL), a tricyclic antidepressant, has been reported to cause various adverse effects, particularly hepatotoxicity. The mechanisms of ATL-induced hepatotoxicity remain unknown. The study was performed to identify the olefin epoxidation metabolite of ATL and determine the possible toxicity mechanism. Two glutathione (GSH) conjugates (M1 and M2) and two N-acetylcysteine (NAC) conjugates (M3 and M4) were detected in rat liver microsomal incubations supplemented with GSH and NAC, respectively. Moreover, M1/M2 and M3/M4 were respectively found in ATL-treated rat primary hepatocytes and in bile and urine of rats given ATL. Recombinant P450 enzyme incubations demonstrated that CYP3A4 was the primary enzyme involved in the olefin epoxidation of ATL. Treatment of hepatocytes with ATL resulted in significant cell death. Inhibition of CYP3A attenuated the susceptibility to the observed cytotoxicity of ATL. The metabolic activation of ATL most likely participates in the cytotoxicity of ATL.


Asunto(s)
Amitriptilina , Citocromo P-450 CYP3A , Compuestos Epoxi , Hepatocitos , Microsomas Hepáticos , Ratas Sprague-Dawley , Animales , Amitriptilina/metabolismo , Ratas , Citocromo P-450 CYP3A/metabolismo , Microsomas Hepáticos/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Masculino , Compuestos Epoxi/metabolismo , Compuestos Epoxi/toxicidad , Compuestos Epoxi/química , Glutatión/metabolismo , Células Cultivadas
12.
J Neural Eng ; 21(3)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38806037

RESUMEN

Objective. Motor-related brain-computer interface (BCI) have a broad range of applications, with the detection of premovement intentions being a prominent use case. However, the electroencephalography (EEG) features during the premovement phase are not distinctly evident and are susceptible to attentional influences. These limitations impede the enhancement of performance in motor-based BCI. The objective of this study is to establish a premovement BCI encoding paradigm that integrates the preparatory movement state and validates its feasibility in improving the detection of movement intentions.Methods. Two button tasks were designed to induce subjects into a preparation state for two movement intentions (left and right) based on visual guidance, in contrast to spontaneous premovement. The low frequency movement-related cortical potentials (MRCPs) and high frequency event-related desynchronization (ERD) EEG data of 14 subjects were recorded. Extracted features were fused and classified using task related common spatial patterns (CSP) and CSP algorithms. Differences between prepared premovement and spontaneous premovement were compared in terms of time domain, frequency domain, and classification accuracy.Results. In the time domain, MRCPs features reveal that prepared premovement induce lower amplitude and earlier latency on both contralateral and ipsilateral motor cortex compared to spontaneous premovement, with susceptibility to the dominant hand's influence. Frequency domain ERD features indicate that prepared premovement induce lower ERD values bilaterally, and the ERD recovery speed after button press is the fastest. By using the fusion approach, the classification accuracy increased from 78.92% for spontaneous premovement to 83.59% for prepared premovement (p< 0.05). Along with the 4.67% improvement in classification accuracy, the standard deviation decreased by 0.95.Significance. The research findings confirm that incorporating a preparatory state into premovement enhances neural representations related to movement. This encoding enhancement paradigm effectively improves the performance of motor-based BCI. Additionally, this concept has the potential to broaden the range of decodable movement intentions and related information in motor-related BCI.


Asunto(s)
Interfaces Cerebro-Computador , Electroencefalografía , Movimiento , Humanos , Movimiento/fisiología , Masculino , Electroencefalografía/métodos , Femenino , Adulto , Adulto Joven , Desempeño Psicomotor/fisiología , Intención , Algoritmos
13.
Integr Zool ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724481

RESUMEN

Rattus species are thought to live only at altitudes less than 2500 m, but the Asian house rat (R. tanezumi) (RT) has recently expanded to altitudes greater than 3500 m in China. Other Rattus species, especially brown rats (R. norvegicus) (RN), still reach only low altitudes on the Tibetan Plateau. Comparative genomics revealed the positive selection of hypoxia-inducible transcription factors 1 and 2 (HIFs) in RT, with the rapid evolution of HIF pathway genes in RT and Mus musculus (MM) but not RN or R. rattus. Population genomics revealed that genes associated with energy metabolism and oxygen transport were positively selected in RT compared with the other four Rattus species, and two specific substitutions (arginine 31 serine and leucine 33 methionine) were identified in the hemoglobin subunit beta (HBB) in RT. The above results suggested that RT possesses unique genetic adaptations to hypoxia, which was further confirmed by behavioral experiments on RT and RN. Normobaric hypoxia significantly reduced locomotion in RN but not in RT. Moreover, through intraspecific transcriptome analysis, the expression of Hbb and genes related to angiogenesis, oxygen transport, and glycolysis was upregulated, and the expression of genes associated with immunological functions in the liver, lungs, and/or sperm was downregulated in RT compared to those in RN. Interspecific transcriptome analysis further revealed that HIF-1α plays a role in modulating the hypoxic adaptation of RT rather than RN. Our work provides genomic, behavioral, and physiological insights into why RT, but not other Rattus species, could invade the Tibetan Plateau.

14.
Biotechnol J ; 19(5): e2400014, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38719614

RESUMEN

Microbial production of L-malic acid from renewable carbon sources has attracted extensive attention. The reduced cofactor NADPH plays a key role in biotransformation because it participates in both biosynthetic reactions and cellular stress responses. In this study, NADPH or its precursors nicotinamide and nicotinic acid were added to the fermentation medium of Aspergillus niger RG0095, which significantly increased the yield of malic acid by 11%. To further improve the titer and productivity of L-malic acid, we increased the cytoplasmic NADPH levels of A. niger by upregulating the NAD kinases Utr1p and Yef1p. Biochemical analyses demonstrated that overexpression of Utr1p and Yef1p reduced oxidative stress, while also providing more NADPH to catalyze the conversion of glucose into malic acid. Notably, the strain overexpressing Utr1p reached a malate titer of 110.72 ± 1.91 g L-1 after 108 h, corresponding to a productivity of 1.03 ± 0.02 g L-1 h-1. Thus, the titer and productivity of malate were increased by 24.5% and 44.7%, respectively. The strategies developed in this study may also be useful for the metabolic engineering of fungi to produce other industrially relevant bulk chemicals.


Asunto(s)
Aspergillus niger , Fermentación , Malatos , Ingeniería Metabólica , NADP , Aspergillus niger/metabolismo , Aspergillus niger/genética , Malatos/metabolismo , Ingeniería Metabólica/métodos , NADP/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glucosa/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo
15.
Acta Pharmacol Sin ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760544

RESUMEN

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

16.
J Am Chem Soc ; 146(15): 10785-10797, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38573588

RESUMEN

The anti-Stokes shift represents the capacity of photon upconversion to convert low-energy photons to high-energy photons. Although triplet exciton-mediated photon upconversion presents outstanding performance in solar energy harvesting, photoredox catalysis, stereoscopic 3D printing, and disease therapeutics, the interfacial multistep triplet exciton transfer leads to exciton energy loss to suppress the anti-Stokes shift. Here, we report near infrared-II (NIR-II) excitable triplet exciton-mediated photon upconversion using a hybrid photosensitizer consisting of lead sulfide quantum dots (PbS QDs) and new surface ligands of thiophene-substituted diketopyrrolopyrrole (Th-DPP). Under 1064 nm excitation, this photon upconversion revealed a record-corrected upconversion efficiency of 0.37% (normalized to 100%), with the anti-Stokes shift (1.07 eV) approaching the theoretical limit (1.17 eV). The observation of this unexpected result is due to our discovery of the presence of a weak interaction between the sulfur atom on Th-DPP and Pb2+ on the PbS QDs surface, facilitating electronic coupling between PbS QDs and Th-DPP, such that the realization of triplet exciton transfer efficiency is close to 100% even when the energy gap is as small as 0.04 eV. With this premise, this photon upconversion as a photocatalyst enables the production of standing organic gel via photopolymerization under 1064 nm illumination, displaying NIR-II photon-driven photoredox catalysis. This research not only establishes the foundation for enhancing the performance of NIR-II excitable photonic upconversion but also promotes its development in photonics and photoredox catalysis.

17.
Food Sci Nutr ; 12(4): 2917-2931, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38628198

RESUMEN

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(4): 426-431, 2024 Apr 15.
Artículo en Chino | MEDLINE | ID: mdl-38632061

RESUMEN

Objective: To explore the effectiveness of using antibiotic bone cement-coated plates internal fixation technology as a primary treatment for Gustilo type ⅢB tibiofibular open fractures. Methods: The clinical data of 24 patients with Gustilo type ⅢB tibiofibular open fractures who were admitted between January 2018 and December 2021 and met the selection criteria was retrospectively analyzed. Among them, there were 18 males and 6 females, aged from 25 to 65 years with an average age of 45.8 years. There were 3 cases of proximal tibial fracture, 6 cases of middle tibial fracture, 15 cases of distal tibial fracture, and 21 cases of fibular fracture. The time from injury to emergency surgery ranged from 3 to 12 hours, with an average of 5.3 hours. All patients had soft tissue defects ranging from 10 cm×5 cm to 32 cm×15 cm. The time from injury to skin flap transplantation for wound coverage ranged from 1 to 7 days, with an average of 4.1 days, and the size of skin flap ranged from 10 cm×5 cm to 33 cm×15 cm. Ten patients had bone defects with length of 2-12 cm (mean, 7.1 cm). After emergency debridement, the tibial fracture end was fixed with antibiotic bone cement-coated plates, and the bone defect area was filled with antibiotic bone cement. Within 7 days, the wound was covered with a free flap, and the bone cement was replaced while performing definitive internal fixation of the fracture. In 10 patients with bone defect, all the bone cement was removed and the bone defect area was grafted after 7-32 weeks (mean, 11.8 weeks). The flap survival, wound healing of the affected limb, complications, and bone healing were observed after operation, and the quality of life was evaluated according to the short-form 36 health survey scale (SF-36 scale) [including physical component summary (PCS) and mental component summary (MCS) scores] at 1 month, 6 months after operation, and at last follow-up. Results: All 24 patients were followed up 14-38 months (mean, 21.6 months). All the affected limbs were successfully salvaged and all the transplanted flaps survived. One case had scar hyperplasia in the flap donor site, and 1 case had hypoesthesia (grade S3) of the skin around the scar. There were 2 cases of infection in the recipient area of the leg, one of which was superficial infection after primary flap transplantation and healed after debridement, and the other was sinus formation after secondary bone grafting and was debrided again 3 months later and treated with Ilizarov osteotomy, and healed 8 months later. The bone healing time of the remaining 23 patients ranged from 4 to 9 months, with an average of 6.1 months. The scores of PCS were 44.4±6.5, 68.3±8.3, 80.4±6.9, and the scores of MCS were 59.2±8.2, 79.5±7.8, 90.0±6.6 at 1 month, 6 months after operation, and at last follow-up, respectively. The differences were significant between different time points ( P<0.05). Conclusion: Antibiotic bone cement-coated plates internal fixation can be used in the primary treatment of Gustilo type ⅢB tibiofibular open fractures, and has the advantages of reduce the risk of infection in fracture fixation, reducing complications, and accelerating the functional recovery of patients.


Asunto(s)
Fracturas Abiertas , Traumatismos de los Tejidos Blandos , Fracturas de la Tibia , Masculino , Femenino , Humanos , Persona de Mediana Edad , Tibia/cirugía , Cementos para Huesos , Fracturas Abiertas/cirugía , Antibacterianos , Cicatriz/cirugía , Estudios Retrospectivos , Calidad de Vida , Resultado del Tratamiento , Fracturas de la Tibia/cirugía , Trasplante de Piel , Fijación Interna de Fracturas/efectos adversos , Traumatismos de los Tejidos Blandos/cirugía
19.
J Evid Based Med ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651546

RESUMEN

OBJECTIVE: This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP). METHODS: We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals. RESULTS: A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6 h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate. CONCLUSIONS: We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.

20.
Injury ; 55(6): 111521, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38584076

RESUMEN

BACKGROUND: The treatment of bone and soft-tissue defects after open fractures remains challenging. This study aimed to evaluate the clinical efficacy of the Masquelet technique combined with the free-flap technique (MFFT) versus the Ilizarov bone transport technique (IBTT) for the treatment of severe composite tibial and soft-tissue defects. METHODS: We retrospectively analysed the data of 65 patients with tibial and soft-tissue defects and Gustilo type IIIB/C open fractures treated at our hospital between April 2015 and December 2021. The patients were divided into two groups based on the treatment method: group A (n = 35) was treated with the MFFT and internal fixation, and group B (n = 30) was treated with the IBTT. RESULTS: The mean follow-up period was 28 months (range 13-133 months). Complete union of both soft-tissue and bone defects was achieved in all cases. The mean bone-union times were 6 months (range 3-12 months) in group A and 11 months (range 6-23 month) in group B, with a significant difference between the two groups (Z = -4.11, P = 0.001). The mean hospital stay was 28 days (range 14-67 d) in group A which was significantly longer than the mean stay of 18 days (range 10-43 d) in group B (Z = -2.608, P = 0.009). There were no significant differences in the infection rate between group A (17.1 %) and group B (26.7%) (χ2 = 0.867, P = 0.352). The Total Physical Health Scores were 81.51 ± 6.86 (range 67-90) in group A and 75.83±16.14 (range 44-98) in group B, with no significant difference between the two groups (t = 1.894, P = 0.063). The Total Mental Health Scores were significantly higher in group A (90.49 ± 6.37; range 78-98) than in group B (84.70 ± 13.72; range 60-98) (t = 2.232, P = 0.029). CONCLUSION: Compared with IBTT, MFFT is a better choice of treatment for open tibial and soft-tissue defects with Gustilo IIIB/C fractures. IBTT is the preferred option when the tibial bone defect is large or if the surgeon's expertise in microsurgery is limited.


Asunto(s)
Fijación Interna de Fracturas , Fracturas Abiertas , Colgajos Tisulares Libres , Técnica de Ilizarov , Traumatismos de los Tejidos Blandos , Fracturas de la Tibia , Humanos , Masculino , Traumatismos de los Tejidos Blandos/cirugía , Femenino , Estudios Retrospectivos , Fracturas Abiertas/cirugía , Adulto , Persona de Mediana Edad , Fracturas de la Tibia/cirugía , Resultado del Tratamiento , Fijación Interna de Fracturas/métodos , Procedimientos de Cirugía Plástica/métodos , Curación de Fractura , Anciano , Adulto Joven , Trasplante Óseo/métodos , Adolescente , Desbridamiento/métodos
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