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1.
Sci Rep ; 14(1): 23365, 2024 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-39375474

RESUMEN

Sensory stimulations at 40 Hz gamma (but not any other frequency), have shown promise in reversing Alzheimer's disease (AD)-related pathologies. What distinguishes 40 Hz? We hypothesized that stimuli at 40 Hz might summate more efficiently (temporal summation) or propagate more efficiently between cortical layers (vertically), or along cortical laminas (horizontally), compared to inputs at 20 or 83 Hz. To investigate these hypotheses, we used brain slices from AD mouse model animals (5xFAD). Extracellular (synaptic) stimuli were delivered in cortical layer 4 (L4). Leveraging a fluorescent voltage indicator (VSFP) expressed in cortical pyramidal neurons, we simultaneously monitored evoked cortical depolarizations at multiple sites, at 1 kHz sampling frequency. Experimental groups (AD-Female, CTRL-Female, AD-Male, and CTRL-Male) were tested at three stimulation frequencies (20, 40, and 83 Hz). Despite our initial hypothesis, two parameters-temporal summation of voltage waveforms and the strength of propagation through the cortical neuropil-did not reveal any distinct advantage of 40 Hz stimulation. Significant physiological differences between AD and Control mice were found at all stimulation frequencies tested, while the 40 Hz stimulation frequency was not remarkable.


Asunto(s)
Enfermedad de Alzheimer , Corteza Cerebral , Modelos Animales de Enfermedad , Células Piramidales , Animales , Enfermedad de Alzheimer/fisiopatología , Ratones , Femenino , Masculino , Corteza Cerebral/fisiopatología , Células Piramidales/fisiología , Ratones Transgénicos
2.
Ultrasound Med Biol ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39317628

RESUMEN

OBJECTIVE: To explore the efficacy and mechanisms of stimulating the nucleus accumbens (NAc) in heroin-addicted mice using focused ultrasound and microbubbles (MBs). METHODS: The conditioned place preference (CPP) method was employed to establish a heroin-addicted mice model. Mice were randomized into control (C), heroin (H), heroin + ultrasound (H + U) and H + U + MBs. Ultrasound (2 MHz fundamental frequency, 1.34 MPa peak-negative pressure, 1 MHz pulse repetition frequency, 5% duty cycle, 15 min/d, over 2 d) was applied to stimulate the NAc in the latter 2 groups. Whereas H + U + MBs received an injection of sulfur hexafluoride MBs during the stimulation. Subsequently, CPP scores, open-field test (OFT), and elevated plus-maze test (EPMT) were conducted to assess behavioral changes in addiction memory, anxiety and exercise status. HE staining was performed to detect pathological structures. Neurotransmitters such as dopamine (DA), serotonin (5-HT) and glutamate (Glu) were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy (TEM) was used to observe ultrastructural changes of synapses in NAc. Immunohistochemistry (IHC) was utilized to detect Cleaved Caspase-3 in the NAc region. Western blotting (WB) was used to detect the protein expression of Cleaved Caspase-3, Bax and Bcl-2 in NAc. RESULTS: HE staining showed small patches of erythrocyte exudation were observed in the NAc and adjacent areas in H + U + MBs. The CPP scores of H + U + MBs were lower (p < 0.05) than H. After ultrasound treatment, all indices of the OFT and EPMT in H + U + MBs were significantly higher than H (p < 0.05). UPLC-MS/MS revealed that the levels of DA, 5-HT and Glu in H + U + MBs were lower than H (p < 0.01). TEM showed decrease the number of synapses (p < 0.05), and noticeable swelling of mitochondria, membrane damage, as well as damage to the cristae. Further detection by IHC and WB showed that the pro-apoptotic proteins Cleaved Caspase-3 and Bax increased and Bcl-2 decreased as anti-apoptotic proteins after ultrasound combined with MBs (p < 0.05). CONCLUSION: Focused ultrasound combined with MBs stimulate the NAc can weaken the addictive memory and improve anxiety of heroin-related mice. The mechanical effect of ultrasound combined with the cavitation effect may be a potential treatment for addiction.

3.
Nano Lett ; 24(37): 11714-11721, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39240781

RESUMEN

Antiferroelectric materials have shown great potential in electronic devices benefiting from the reversible phase transition between ferroelectric and antiferroelectric phases. Understanding the dipole arrangements and clear phase transition pathways is crucial for design of antiferroelectric materials-based energy storage and conversion devices. However, the specific phase transition details remain largely unclear and even controversial to date. Here, we have grown a series of PbZrO3 on SrTiO3 substrates and elucidated the fine atom structures and phase transition pathways using atomic-resolution transmission electron microscopy. Specifically, a roadmap for ferroelectric to antiferroelectric phase transitions, here with increasing film thickness, is determined as ferroelectric rhombohedral (R3c)-ferroelectric monoclinic (Pc)-ferrielectric orthorhombic (Ima2)-antiferroelectric orthorhombic (Pbam), where Pc and Ima2 phases act as structural bridges. Moreover, the phase transition pathway is strongly related to the synergistic effect of oxygen octahedral tilting and cation displacement. These findings provide an insightful understanding for the theories and related properties of antiferroelectrics.

4.
Int J Mol Sci ; 25(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39273445

RESUMEN

Limb muscle is responsible for physical activities and myogenic cell migration during embryogenesis is indispensable for limb muscle formation. Maternal obesity (MO) impairs prenatal skeletal muscle development, but the effects of MO on myogenic cell migration remain to be examined. C57BL/6 mice embryos were collected at E13.5. The GeoMx DSP platform was used to customize five regions along myogenic cell migration routes (myotome, dorsal/ventral limb, limb stroma, limb tip), and data were analyzed by GeomxTools 3.6.0. A total of 2224 genes were down-regulated in the MO group. The GO enrichment analysis showed that MO inhibited migration-related biological processes. The signaling pathways guiding myogenic migration such as hepatocyte growth factor signaling, fibroblast growth factor signaling, Wnt signaling and GTPase signaling were down-regulated in the MO E13.5 limb tip. Correspondingly, the expression levels of genes involved in myogenic cell migration, such as Pax3, Gab1, Pxn, Tln2 and Arpc, were decreased in the MO group, especially in the dorsal and ventral sides of the limb. Additionally, myogenic differentiation-related genes were down-regulated in the MO limb. MO impedes myogenic cell migration and differentiation in the embryonic limb, providing an explanation for the impairment of fetal muscle development and offspring muscle function due to MO.


Asunto(s)
Diferenciación Celular , Movimiento Celular , Desarrollo de Músculos , Obesidad Materna , Animales , Movimiento Celular/genética , Ratones , Femenino , Desarrollo de Músculos/genética , Diferenciación Celular/genética , Embarazo , Obesidad Materna/metabolismo , Obesidad Materna/genética , Ratones Endogámicos C57BL , Regulación del Desarrollo de la Expresión Génica , Transcriptoma , Desarrollo Embrionario/genética , Extremidades/embriología , Perfilación de la Expresión Génica , Transducción de Señal , Músculo Esquelético/metabolismo , Músculo Esquelético/embriología
5.
Foods ; 13(16)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39200408

RESUMEN

The persistence of Listeria monocytogenes biofilms on equipment surfaces poses a significant risk of cross-contamination, necessitating effective surface decontamination strategies. This study assessed the effectiveness of hurdle treatments combining peroxyacetic acid (PAA) and saturated steam against 7-day-old L. innocua (a non-pathogenic surrogate for L. monocytogenes) biofilms on stainless steel (SS), polyester (PET), and rubber surfaces. Results demonstrated >6 log10 CFU/coupon L. innocua reductions on SS and PET surfaces after PAA (40 ppm, 1 min) followed by steam treatment (100 °C, 6 s). On rubber surfaces, PAA (80 ppm, 1 min) followed by steam treatment (100 °C, 6 s) resulted in ~5 log10 CFU/coupon L. innocua reduction. The presence of apple juice soil reduced the efficacy of hurdle treatments, with PAA (40 ppm, 1 min) and steam exposure (6 s) resulting in 5.6, 5.8, and 4.2 log10 CFU/coupon reductions of L. innocua on SS, PET, and rubber, respectively. The efficacy of this antimicrobial combination was further reduced by surface defects, especially in the presence of organic matter. Nevertheless, the treatment still achieved >5 log10 CFU/coupon reductions of L. innocua on worn SS and PET soiled with apple juice and ~4.5 log10 CFU/coupon reduction on worn, soiled rubber surfaces. These findings highlight that PAA treatments followed by a brief steam exposure are effective strategies for controlling Listeria on food-contact surfaces.

6.
ACS Nano ; 18(33): 22104-22121, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39102149

RESUMEN

Digital light processing (DLP) bioprinting, known for its high resolution and speed, enables the precise spatial arrangement of biomaterials and has become integral to advancing tissue engineering and regenerative medicine. Nevertheless, inherent light scattering presents significant challenges to the fidelity of the manufactured structures. Herein, we introduce a photoinhibition strategy based on Rutin nanoparticles (Rnps), attenuating the scattering effect through concurrent photoabsorption and free radical reaction. Compared to the widely utilized biocompatible photoabsorber tartrazine (Tar), Rnps-infused bioink enhanced printing speed (1.9×), interlayer homogeneity (58% less overexposure), resolution (38.3% improvement), and print tolerance (3× high-precision range) to minimize trial-and-error. The biocompatible and antioxidative Rnps significantly improved cytocompatibility and exhibited resistance to oxidative stress-induced damage in printed constructs, as demonstrated with human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). The related properties of Rnps facilitate the facile fabrication of multimaterial, heterogeneous, and cell-laden biomimetic constructs with intricate structures. The developed photoinhibitor, with its profound adaptability, promises wide biomedical applications tailored to specific biological requirements.


Asunto(s)
Bioimpresión , Luz , Nanopartículas , Rutina , Humanos , Rutina/química , Rutina/farmacología , Nanopartículas/química , Ingeniería de Tejidos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
7.
J Headache Pain ; 25(1): 130, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135164

RESUMEN

BACKGROUND: While growing evidence suggests a relationship between migraine and cardiovascular disease, the genetic evidence for a causal relationship between migraine and cardiovascular disease is still scarce. Investigating the causal association between migraine and cardiovascular disease is vital. METHODS: We carried out a bidirectional Mendelian randomization (MR) study including discovery samples and replication samples using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables. Four different MR techniques-Inverse variance weighted (IVW), MR ‒Egger, weighted median, and weighted mode-as well as various sensitivity analyses-Cochran's Q, IVW radial, leave-one-out (LOO), and MR-PRESSO-were utilized to investigate the causal relationship between cardiovascular disease and migraine. RESULTS: The protective causal effects of genetically predicted migraine on coronary artery disease (OR, 0.881; 95% CI 0.790-0.982; p = 0.023) and ischemic stroke (OR, 0.912; 95% CI 0.854-0.974; p = 0.006) were detected in forward MR analysis but not in any other cardiovascular disease. Consistently, we also discovered protective causal effects of coronary atherosclerosis (OR, 0.865; 95% CI 0.797-0.940; p = 0.001) and myocardial infarction (OR, 0.798; 95% CI 0.668-0.952; p = 0.012) on migraine in reverse MR analysis. CONCLUSION: We found a potential protective effect of migraine on coronary artery disease and ischemic stroke and a potential protective effect of coronary atherosclerosis and myocardial infarction on migraine. We emphasised epidemiological and genetic differences and the need for long-term safety monitoring of migraine medications and future research to improve cardiovascular outcomes in migraine patients.


Asunto(s)
Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/epidemiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Causalidad , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad
8.
Front Neurol ; 15: 1400810, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39175760

RESUMEN

Introduction: Sleep disorders are prevalent and significant among individuals receiving methadone maintenance treatment (MMT), adversely affecting their quality of life and treatment adherence. While cerebral blood flow (CBF) plays a crucial role in the development of various diseases, its relationship with sleep disorders remains uncertain. This observational study focuses on possible correlations between CBF and poor subjective sleep quality in MMT patients. Methods: A total of 75 participants with a history of MMT were recruited and assessed using pseudo-continuous arterial spin labeling magnetic resonance imaging to determine CBF. A LAASO regression model was employed to identify the region of interest (ROI) most associated with sleep disturbance. The association between the CBF of the ROI and the Pittsburgh Sleep Quality Index (PSQI) was examined using regression analyses. Age, gender, BMI, history of hypertension, diabetes, hyperlipidemia, and methadone withdrawal were included as covariates. Results: Among MMT patients with poor subjective sleep quality, significantly higher CBF was observed in the right paracentral lobule (56.1057 ± 11.1624 ml/100 g/min, p = 0.044), right cerebelum_3 (56.6723 ± 15.3139 ml/100 g/min, p = 0.026), right caudate nucleus (48.9168 ± 6.9910 ml/100 g/min, p = 0.009), and left caudate nucleus (47.6207 ± 6.1374 ml/100 g/min, p = 0.006). Furthermore, a positive correlation was found between CBF in the right paracentral lobule and the total PSQI score (ß = 0.1135, p = 0.0323), with the association remaining significant even after adjustment for covariates (ß = 0.1276, p = 0.0405). Conclusion: MMT patients with poor subjective sleep quality exhibited significantly altered CBF in multiple brain regions. The association between increased CBF in the right paracentral lobule and subjective sleep quality in MMT patients could be crucial in understanding sleep disorders in individuals undergoing MMT. Clinical trial registration: https://www.chictr.org.cn/, identifier: ChiCTR2100051931.

9.
Zhen Ci Yan Jiu ; 49(7): 736-742, 2024 Jul 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39020492

RESUMEN

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.


Asunto(s)
Cuerpo Estriado , Ferroptosis , Ratones Endogámicos C57BL , Moxibustión , Neuronas , Enfermedad de Parkinson , Animales , Ferroptosis/genética , Ratones , Cuerpo Estriado/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Masculino , Humanos , Neuronas/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Regulación hacia Abajo , Actividad Motora , Modelos Animales de Enfermedad
10.
Oncol Lett ; 28(2): 384, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38966578

RESUMEN

The aim of the present study was to evaluate the diagnostic value of plasma human cystatin-S (CST4) in patients with digestive system malignant tumors. CST4 and tumor markers, such as α-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, CA153 and CA724, were detected in blood samples from 100 patients with a digestive system malignant tumor and 100 patients with benign digestive system diseases. The tumor markers AFP, CEA, CA199, CA125, CA153 and CA724 were detected using an electrochemiluminescence immunoassay, and CST4 levels were detected using a human CST4 ELISA kit. The results demonstrated that the sensitivities of AFP and CA153 (both 5.00%) were significantly lower than that of CST4 (38.00%) in the diagnosis of digestive system malignancy (P<0.001), and CA724 (18.00%) was also less sensitive than CST4 (P<0.05). The sensitivities of CA199 (26.00%), CEA (31.00%) and CA125 (25.00%) were similar to that of CST4 (P>0.05). There was no significant difference in the CEA, CA125, CA724 and CST4 specificities (P>0.05), which were 91.00, 95.00, 94.00 and 83.00%, respectively. The specificities of AFP (99.00%), CA199 (98.00%) and CA153 (100.00%) were significantly higher than that of CST4 (P<0.01). By constructing a receiver operating characteristic curve and comparing the area under the curve as well as sensitivity, the findings of the present study demonstrated that combining CST4 with AFP, CEA, CA199, CA125, CA153 and CA724 can significantly enhance the diagnostic sensitivity for malignancies of the digestive system. However, the introduction of CST4 into the traditional diagnostic groups (CEA + AFP, CA199 + CA125 + CA153 + CA724 and AFP + CEA + CA199 + CA125 + CA153 + CA724) resulted in an increased sensitivity and loss of specificity, thereby not offering significant advantages in terms of comprehensive diagnostic efficiency compared with the traditional diagnostic groups. In conclusion, CST4 detection may be a promising diagnostic tool. Nonetheless, the potential false positive results in tumor diagnosis should be taken into consideration when developing new diagnostic groups involving CST4.

11.
Animals (Basel) ; 14(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38998005

RESUMEN

Egg production traits are crucial in the poultry industry, including age at first egg (AFE), egg number (EN) at different stages, and laying rate (LR). Ducks exhibit higher egg production capacity than other poultry species, but the genetic mechanisms are still poorly understood. In this study, we collected egg-laying data of 618 Peking ducks from 22 to 66 weeks of age and genotyped them by whole-genome resequencing. Genetic parameters were calculated based on SNPs, and a genome-wide association study (GWAS) was performed for these traits. The SNP-based heritability of egg production traits ranged from 0.09 to 0.54. The GWAS identified nine significant SNP loci associated with AFE and egg number from 22 to 66 weeks. These loci showed that the corresponding alleles were positively correlated with a decrease in the traits. Moreover, three potential candidate genes (ENSAPLG00020011445, ENSAPLG00020012564, TMEM260) were identified. Functional enrichment analyses suggest that specific immune responses may have a critical impact on egg production capacity by influencing ovarian function and oocyte maturation processes. In conclusion, this study deepens the understanding of egg-laying genetics in Peking duck and provides a sound theoretical basis for future genetic improvement and genomic selection strategies in poultry.

12.
Water Res ; 261: 122027, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39018904

RESUMEN

Depletion of dissolved oxygen (DO) is a significant incentive for biological catastrophic events in freshwater lakes. Although predicting the DO concentrations in lakes with high-frequency real-time data to prevent hypoxic events is effective, few related experimental studies were made. In this study, a short-term predicting model was developed for DO concentrations in three problematic areas in China's Chaohu Lake. To predict the DO concentrations at these representative sites, which coincide with biological abnormal death areas, water quality indicators at the three sampling sites and hydrometeorological features were adopted as input variables. The monitoring data were collected every 4 h between 2020 and 2023 and applied separately to train and test the model at a ratio of 8:2. A new AC-BiLSTM coupling model of the convolution neural network (CNN) and the bidirectional long short-term memory (BiLSTM) with the attention mechanism (AM) was proposed to tackle characteristics of discontinuous dynamic change of DO concentrations in long time series. Compared with the BiLSTM and CNN-BiLSTM models, the AC-BiLSTM showed better performance in the evaluation criteria of MSE, MAE, and R2 and a stronger ability to capture global dependency relationships. Although the prediction accuracy of hypoxic events was slightly worse, the general time series characteristics of abrupt DO depletion were captured. Water temperature regularly affects DO concentrations due to its periodic variations. The high correlation and the universal importance of total nitrogen (TN) and total phosphorus (TP) with DO reveals that point source pollution are critical cause of DO depletion in the freshwater lake. The importance of NTU at the Zhong Miao Station indicates the self-purification capacity of the lake is affected by the flow rate changes brought by the tributaries. Calculating linear correlations of variables in conjunction with a permutation variable importance analysis enhanced the interpretability of the proposed model results. This study demonstrates that the AC-BiLSTM model can complete the task of short-term prediction of DO concentration of lakes and reveal its response features of timing and magnitude of abrupt DO depletion.


Asunto(s)
Lagos , Redes Neurales de la Computación , Oxígeno , Lagos/química , Oxígeno/análisis , China , Monitoreo del Ambiente/métodos , Calidad del Agua
13.
Genes (Basel) ; 15(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39062614

RESUMEN

The incidence of colorectal cancer (CRC) is closely linked to metabolic diseases. Accumulating evidence suggests the regulatory role of AMP-activated protein kinase (AMPK) in cancer metabolic reprogramming. In this study, wild-type and AMPK knockout mice were subjected to azoxymethane-induced and dextran sulfate sodium (AOM/DSS)-promoted colitis-associated CRC induction. A stable AMPK-deficient Caco-2 cell line was also established for the mechanistic studies. The data showed that AMPK deficiency accelerated CRC development, characterized by increased tumor number, tumor size, and hyperplasia in AOM/DSS-treated mice. The aggravated colorectal tumorigenesis resulting from AMPK ablation was associated with reduced α-ketoglutarate production and ten-eleven translocation hydroxylase 2 (TET2) transcription, correlated with the reduced mismatch repair protein mutL homolog 1 (MLH1) protein. Furthermore, in AMPK-deficient Caco-2 cells, the mRNA expression of mismatch repair and tumor suppressor genes, intracellular α-ketoglutarate, and the protein level of TET2 were also downregulated. AMPK deficiency also increased hypermethylation in the CpG islands of Mlh1 in both colonic tissues and Caco-2 cells. In conclusion, AMPK deficiency leads to reduced α-ketoglutarate concentration and elevates the suppressive epigenetic modifications of tumor suppressor genes in gut epithelial cells, thereby increasing the risk of colorectal tumorigenesis. Given the modifiable nature of AMPK activity, it holds promise as a prospective molecular target for the prevention and treatment of CRC.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Azoximetano , Carcinogénesis , Neoplasias Colorrectales , Metilación de ADN , Dioxigenasas , Animales , Humanos , Ratones , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Azoximetano/toxicidad , Azoximetano/efectos adversos , Células CACO-2 , Carcinogénesis/genética , Colitis/inducido químicamente , Colitis/genética , Colitis/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/etiología , Sulfato de Dextran/toxicidad , Dioxigenasas/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Ácidos Cetoglutáricos/metabolismo , Ratones Noqueados , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo
14.
J Appl Microbiol ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39076016

RESUMEN

AIMS: The survival of inoculated Escherichia coli on Fuji apples in Washington State orchards was studied, considering evaporative cooling, canopy location, year, and region, with the examination of sunlight exposure and inoculation levels in year 2. METHODS AND RESULTS: Rifampicin-resistant E. coli was applied to Fuji apples. Initial concentrations for the high-inoculation study were 7.4 ± 0.3 log10 CFU per apple and 3.4 ± 0.3 log10 CFU per apple for the low-inoculation study. Enumeration of E. coli was conducted at 0, 2, 10, 18, 34, 42, 58, 82, 106, and 154 h after inoculation. Results were analyzed using Tukey's honest significance difference test and a log-linear model. Log-linear, Weibull, and Biphasic models characterized E. coli die-off patterns for high and low inoculations. The application of evaporative overhead cooling water did not significantly influence E. coli survival on Fuji apples; inoculation level and sunlight exposure were significant factors in a log-linear model. E. coli decreased by 5.5 ± 1.3 and 3.3 ± 0.4 log10 CFU per apple for high and low inoculated apples, respectively, by 154 h. The Biphasic model best explained the die-off pattern for high and low-inoculated Fuji apples. CONCLUSIONS: Overhead evaporative cooling, a useful fruit quality practice, did not impact the survival of generic E. coli on Fuji apple surfaces. The significant impact of sunlight exposure and inoculation levels on die-off highlights the importance of ultraviolet radiation in risk reduction and the need for various inoculum concentrations in preharvest field studies.

15.
Curr Res Food Sci ; 8: 100782, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939610

RESUMEN

Discriminant analysis of similar food samples is an important aspect of achieving food quality control. The effective combination of Raman spectroscopy and machine learning algorithms has become an extremely attractive approach to develop intelligent discrimination techniques. Feature spectral analysis can help researchers gain a deeper understanding of the data patterns in food quality discrimination. Herein, this work takes the discrimination of three brands of dairy products as an example to investigate the Raman spectral feature based on the support vector machines (SVM), extreme learning machines (ELM) and convolutional neural network (CNN) algorithms. The results show that there are certain differences in the optimal spectral feature interval corresponding to different machine learning algorithms. Selecting the appropriate spectral feature interval can maintain high recognition accuracy and improve the computational efficiency of the algorithm. For example, the SVM algorithm has a recognition accuracy of 100% in the 890-980 cm-1, 1410-1500 cm-1 fusion spectral range, which takes about 200 s. The ELM algorithm also has a recognition accuracy of 100% in the 890-980 cm-1, 1410-1500 cm-1 fusion spectral range, which takes less than 0.3 s. The CNN algorithm has a recognition accuracy of 100% in the 890-980 cm-1, 1050-1180 cm-1, 1410-1500 cm-1 fusion spectral range, which takes about 80 s. In addition, by analyzing the distribution of spectral feature intervals based on Euclidean distance, the distribution of experimental samples based on feature spectra is visually displayed. Through the spectral feature analysis process of similar samples, a set of analysis strategies is provided to deeply reveal the data foundation of classification algorithms, which can provide reference for the analysis of relevant discriminative research patterns.

16.
Artículo en Inglés | MEDLINE | ID: mdl-38889747

RESUMEN

BACKGROUND: Ferroptosis is emerging as a critical pathway in ischemia/reperfusion (I/R) injury, contributing to compromised cardiac function and predisposing individuals to sepsis and myocardial failure. The study investigates the underlying mechanism of dexmedetomidine (DEX) in hypoxia/reoxygenation (H/R)-induced ferroptosis in cardiomyocytes, aiming to identify novel targets for myocardial I/R injury treatment. METHODS: H9C2 cells were subjected to H/R and treated with varying concentrations of DEX. Additionally, H9C2 cells were transfected with miR-141-3p inhibitor followed by H/R treatment. Levels of miR-141-3p, long noncoding RNA (lncRNA) taurine upregulated 1 (TUG1), Fe2+, glutathione (GSH), and malondialdehyde were assessed. Reactive oxygen species (ROS) generation was measured via fluorescent labeling. Expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) was determined using Western blot. The interaction between miR-141-3p and lncRNA TUG1 was evaluated through RNA pull-down assay and dual-luciferase reporter gene assays. The stability of lncRNA TUG1 was assessed using actinomycin D. RESULTS: DEX ameliorated H/R-induced cardiomyocyte injury and elevated miR-141-3p expression in cardiomyocytes. DEX treatment increased cell viability, Fe2+, and ROS levels while decreasing ACSL4 protein expression. Furthermore, DEX upregulated GSH and GPX4 protein levels. miR-141-3p targeted lncRNA TUG1, reducing its stability and overall expression. Inhibition of miR-141-3p or overexpression of lncRNA TUG1 partially reversed the inhibitory effect of DEX on H/R-induced ferroptosis in cardiomyocytes. CONCLUSION: DEX mitigated H/R-induced ferroptosis in cardiomyocytes by upregulating miR-141-3p expression and downregulating lncRNA TUG1 expression, unveiling a potential therapeutic strategy for myocardial I/R injury.

17.
Front Psychiatry ; 15: 1402533, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827441

RESUMEN

Introduction: Methamphetamine is currently one of the most commonly used addictive substances with strong addiction and a high relapse rate. This systematic review aims to examine the effectiveness of physical activity in improving negative emotions, cognitive impairment, and drug craving in people with methamphetamine use disorder (MUD). Methods: A total of 17 studies out of 133 found from Embase and PubMed were identified, reporting results from 1836 participants from MUD populations. Original research using clearly described physical activity as interventions and reporting quantifiable outcomes of negative mood, cognitive function and drug craving level in people with MUD were eligible for inclusion. We included prospective studies, randomized controlled trials, or intervention studies, focusing on the neurological effects of physical activity on MUD. Results: Taken together, the available clinical evidence showed that physical activity-based interventions may be effective in managing MUD-related withdrawal symptoms. Discussion: Physical exercise may improve drug rehabilitation efficiency by improving negative emotions, cognitive behaviors, and drug cravings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024530359.

18.
Compr Rev Food Sci Food Saf ; 23(3): e13348, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38720587

RESUMEN

Listeria monocytogenes biofilms formed on food-contact surfaces within food-processing facilities pose a significant challenge, serving as persistent sources of cross-contamination. In this review, we examined documented cases of foodborne outbreaks and recalls linked to L. monocytogenes contamination on equipment surfaces and in the food production environment, provided an overview of the prevalence and persistence of L. monocytogenes in different food-processing facilities, and discussed environmental factors influencing its biofilm formation. We further delved into antimicrobial interventions, such as chemical sanitizers, thermal treatments, biological control, physical treatment, and other approaches for controlling L. monocytogenes biofilms on food-contact surfaces. This review provides valuable insights into the persistent challenge of L. monocytogenes biofilms in food processing, offering a foundation for future research and practical strategies to enhance food safety.


Asunto(s)
Biopelículas , Microbiología de Alimentos , Listeria monocytogenes , Listeria monocytogenes/fisiología , Biopelículas/crecimiento & desarrollo , Manipulación de Alimentos/métodos , Contaminación de Alimentos/prevención & control , Contaminación de Equipos/prevención & control
19.
Arch Virol ; 169(5): 114, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700535

RESUMEN

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/virología , Neoplasias Gástricas/patología , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/mortalidad , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Pronóstico , Estudios Retrospectivos , Anciano , Adulto , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antígeno Ki-67/metabolismo , ARN Viral/genética , Gastrectomía
20.
Heliyon ; 10(9): e30576, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38765082

RESUMEN

Background: The incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with suspected lung cancer. However, a high rate of false positives and concerns regarding the radiation-related cancer risk of repeated CT scanning remain major obstacles to its wide application. This study aimed to investigate the clinical value of seven tumour-associated autoantibodies (7-TAAbs) in the differentiation of malignant pulmonary tumours from benign ones and the early detection of lung cancer in routine clinical practice. Methods: We included 377 patients who underwent both the 7-TAAbs panel test and LDCT screening, and were diagnosed with pulmonary nodules using LDCT. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels antibodies for P53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, and MAGE-A1. The relationships between the positive rates of the 7-TAAbs and the patient sex, and age, and the number, size, and composition of pulmonary nodules were analysed. We then statistically evaluated the clinical application value. Results: The positive rates of the 7-TAAbs did not correlate with sex, age, number, size, or composition of pulmonary nodules. The serum antibody level of GBU4-5 in patients with pulmonary nodules tended to increase with age; the serum antibody level of SOX2 tended to increase with nodule size and was the highest among patients with mixed ground-glass opacity (mGGO) nodules. The antibody positive rate for CAGE in female patients with pulmonary nodules was significantly higher than that in male patients (P < 0.05). The positive rate of GBU4-5 antibody in patients aged 60 years and above was higher than that in younger patients (P < 0.05). The positive rate of GAGE7 antibody in patients with pulmonary nodules sized 8-20 mm was also significantly higher than that in patients with pulmonary nodules sized less than 8 mm (P < 0.01). Significant differences were observed in the GAGE7 antibody levels of patients with pulmonary nodules of different compositions (P < 0.01). The positive rate of the 7-TAAbs panel test in patients with lung cancer was significantly higher than in patients with pulmonary nodules (P < 0.01). Serum levels of P53, SOX2, GBU4-5, and MAGE-A1 antibodies were significantly higher in patients with lung cancer than in those with pulmonary nodules (P < 0.05). Conclusion: The low positive rates of serum 7-TAAbs in patients with lung cancer and pulmonary nodules may be related to different case selection, population differences, geographical differences, different degrees of progression, and detection methods. The combined detection of 7-TAAbs has some clinical value for screening and early detection of lung cancer.

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