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1.
Cell ; 186(17): 3726-3743.e24, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37442136

RESUMEN

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.


Asunto(s)
Corteza Cerebral , Macaca , Análisis de la Célula Individual , Transcriptoma , Animales , Humanos , Ratones , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Macaca/metabolismo , Transcriptoma/genética
2.
Nucleic Acids Res ; 51(8): 4000-4011, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-36912079

RESUMEN

Two types of glycyl-tRNA synthetase (GlyRS) are known, the α2 and the α2ß2 GlyRSs. Both types of synthetase employ a class II catalytic domain to aminoacylate tRNAGly. In plastids and some bacteria, the α and ß subunits are fused and are designated as (αß)2 GlyRSs. While the tRNA recognition and aminoacylation mechanisms are well understood for α2 GlyRSs, little is known about the mechanisms for α2ß2/(αß)2 GlyRSs. Here we describe structures of the (αß)2 GlyRS from Oryza sativa chloroplast by itself and in complex with cognate tRNAGly. The set of structures reveals that the U-shaped ß half of the synthetase selects the tRNA in a two-step manner. In the first step, the synthetase engages the elbow and the anticodon base C35 of the tRNA. In the second step, the tRNA has rotated ∼9° toward the catalytic centre. The synthetase probes the tRNA for the presence of anticodon base C36 and discriminator base C73. This intricate mechanism enables the tRNA to access the active site of the synthetase from a direction opposite to that of most other class II synthetases.


Asunto(s)
Glicina-ARNt Ligasa , Glicina-ARNt Ligasa/genética , Anticodón , ARN de Transferencia de Glicerina/química , ARN de Transferencia , Plastidios
3.
J Clin Gastroenterol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38896424

RESUMEN

OBJECTIVE: The diagnosis of RGERD in patients typically involves 24-hour esophageal pH monitoring, but due to its invasiveness and low patient compliance, new screening methods are needed. In this study, a lactulose breath test (LBT) was conducted to detect the growth of small intestine bacteria (SIBO) and explore the potential relationship between LBT and RGERD to identify a new treatment method for RGERD. METHODS: A total of 178 patients with gastroesophageal reflux were enrolled from June 2020 to December 2022 in the Gastroenterology Department, Building 3, the First Affiliated Hospital of Kunming Medical University; these patients included 96 patients with nonrefractory GERD (NRGERD) and 82 patients with RGERD. The Gerd Q score, reflux symptom index (RSI) score, gastroscopy results, clinical symptoms, and other related indicators were collected. Statistical methods were used to analyze the gathered data. RESULTS: The incidence of acid reflux and heartburn in patients with RGERD was significantly greater than that in patients with NRGERD (67.10% vs. 42.70%, P<0.01 and 65.00% vs. 34.40%, P<0.01). The CH4 values of patients with RGERD were significantly greater than those of patients with NRGERD at each time point, and there was a correlation between the CH4 values at 60 min and RGERD (P<0.05). For patients with RGERD, the incidence of abdominal pain, acid regurgitation, and heartburn was greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 57.50%, 69.05% vs. 65.00%, 69.05% vs. 57.50%, P>0.05). The incidence of nausea was also greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 35.00%, P<0.05). CONCLUSION: Increased CH4 levels are correlated with RGERD. In addition, patients with RGERD may develop SIBO after long-term use of PPIs, and interventions involving SIBO could provide new ideas for the treatment of RGERD.

4.
Microbiol Immunol ; 68(7): 213-223, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38747013

RESUMEN

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.


Asunto(s)
Lesión Renal Aguda , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efectos de los fármacos , Limosilactobacillus reuteri/fisiología , Limosilactobacillus reuteri/metabolismo , Animales , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Ratones , Lipopolisacáridos/metabolismo , Masculino , Riñón/microbiología , Riñón/metabolismo , Heces/microbiología , Modelos Animales de Enfermedad , Creatinina/sangre , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos
5.
Chemistry ; 29(39): e202301163, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37093547

RESUMEN

Achieving efficient separation of mono-/multivalent metal ions is essential in various fields, yet it remains a significant challenge. In this work, a metal-organic framework (MOF) array with subnanochannels that exhibit high selectivity and ion permeability in the sieving of mono-/multivalent metal ion was developed. Specifically, we used confined interfacial reaction at room temperature to synthesis the MOF array inside the micrometer through-pores of a polyethylene terephthalate (PET) membrane. The location of the oil/water interface was regulated by adjusting the surface wettability of the PET membrane. By taking advantage of size sieving effect of the subnanochannels of MOF crystals, we were able to effectively separate monovalent metal ions from multivalent metal ions with selectivity reaching up to 3930±373 (e.g., Li+ /Zr4+ ). The fluxes of Li+ ions were observed to be as high as 1.97 mol h-1 m-2 . The MOF array-based membrane with subnanochannels that we have developed exhibits great promise for applications in wastewater treatment, lithium extraction from salt-lake brines, and other related fields.

6.
Scand J Gastroenterol ; 58(6): 684-692, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36546536

RESUMEN

OBJECTIVES: The modified National Institutes of Health (NIH) risk criteria for gastrointestinal stromal tumours (GISTs) have some limitations and need to be improved. METHODS: Patients who underwent radical resection of primary GIST were retrospectively reviewed. Peripheral blood indices including the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) were analysed. Recurrence-free survival (RFS) was calculated and compared. Multivariate analysis was conducted. Area under the receiver operating characteristic curve (ROC) was calculated. RESULTS: A total of 492 patients were enrolled. Tumour size, mitotic index (MI), tumour location and PNI were independent prognostic factors. The modified NIH criteria could not distinguish among very low-, low- and intermediate-risk patients, and PNI was the only independent prognostic factors for them. The five-year RFS rate in the high risk (HR) group was significantly lower. A further modification to the NIH risk criteria was proposed (the 'NIH-PNI stratification'). Non-high risk (NHR) patients were divided into the NHR-PNI-H group (PNI > 48.05) and the NHR-PNI-L group (PNI ≤ 48.05), respectively. HR patients were divided according to tumour size and MI: the HR1, HR2 and HR3 groups. The five-year RFS rates of the NHR-PNI-H, NHR-PNI-L, HR1, HR2 and HR3 groups were 97.3%, 93.5%, 74.1%, 61.7% and 24.4%, respectively (p < .001). The area under the curve (AUC) for the NIH-PNI stratification, modified NIH criteria, NIH criteria (2002), AFIP criteria and nomogram were 0.857, 0.807, 0.817, 0.843 and 0.831, respectively. CONCLUSION: The proposed NIH-PNI stratification was able to distinguish among five groups in terms of risk of recurrence.


A further modification to the NIH risk criteria for GISTs was proposed ('NIH-PNI stratification'). Non-high risk (NHR) patients were divided into NHR-PNI-H and NHR-PNI-L groups. High risk (HR) patients were divided to HR1, HR2 and HR3 groups. The five-year RFS rates were 97.3%, 93.5%, 74.1%, 61.7% and 24.4%, respectively (p < .001). The AUC for the NIH-PNI stratification, modified NIH criteria, NIH criteria (2002), AFIP criteria and nomogram were 0.857, 0.807, 0.817, 0.843 and 0.831.


Asunto(s)
Tumores del Estroma Gastrointestinal , Humanos , Estudios Retrospectivos , Medición de Riesgo , Nomogramas , Linfocitos/patología , Pronóstico
7.
Phys Chem Chem Phys ; 25(34): 23296-23305, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37609804

RESUMEN

In the marine boundary layer (MBL), chlorine (Cl) and chlorine monoxide (ClO) are powerful oxidants with high concentrations. The gas-liquid interface is also ubiquitous in the MBL as a favorable site for atmospheric reactions. Understanding the role of water in Cl/ClO radical chemistry is essential for predicting their behavior in the atmosphere and developing effective strategies for mitigating their harmful effects. However, the research studies on the system of Cl/ClO radicals on the surface of water droplets are still insufficient. In previous studies, we have found unique results related to the hydroxyl radical at the interface using ab initio molecular dynamics (AIMD). In this work, we have used AIMD to investigate interactions between Cl/ClO radicals and water molecules at the gas-liquid interface. Radical mobility, radial distribution functions, coordination, and population analyses were conducted to investigate the surface preference, bonding pattern, and track Cl/ClO radicals in the water droplets. In addition, density functional theory (DFT) analysis was conducted to compare the results at the gas-liquid interface with those in the gas phase. We found that Cl/ClO radicals tend to remain near the gas-liquid interface in water droplet systems and outside of water clusters in gas phase systems. The ClO radical can form O*-H and Cl-O bonds with water molecules; however, neither the O*-O hemibond nor the Cl-H bond was detected in all systems. Different dominant structures were obtained for ClO in the interface and gas phase. The ClO radical can be bonded to one water molecule from its oxygen side, (H2O)0-Cl-O*-(H2O)1 at the interface, or to two water molecules from the chlorine and oxygen sides, (H2O)1-Cl-O*-(H2O)1 in the gas phase. Meanwhile, the Cl radical can only form a dominant structure like Cl*-(H2O)1 at the gas-liquid interface by making a Cl*-O hemibond. Providing a thorough explanation of the Cl/ClO radical behavior at the gas-liquid interface, this study will improve our understanding of the MBL's oxidizing capacity and pollution causes.

8.
Sensors (Basel) ; 23(3)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36772585

RESUMEN

Aiming at the existing Direction of Arrival (DOA) methods based on neural network, a large number of samples are required to achieve signal-scene adaptation and accurate angle estimation. In the coherent signal environment, the problems of a larger amount of training sample data are required. In this paper, the DOA of coherent signal is converted into the DOA parameter estimation of the angle interval of incident signal. The accurate estimation of coherent DOA under the condition of small samples based on meta-reinforcement learning (MRL) is realized. The meta-reinforcement learning method in this paper models the process of angle interval estimation of coherent signals as a Markov decision process. In the inner loop layer, the sequence to sequence (S2S) neural network is used to express the angular interval feature sequence of the incident signal DOA. The strategy learning of the existence of angle interval under small samples is realized through making full use of the context relevance of spatial spectral sequence through S2S neural network. Thus, according to the optimal strategy, the output sequence is sequentially determined to give the angle interval of the incident signal. Finally, DOA is obtained through one-dimensional spectral peak search according to the angle interval obtained. The experiment shows that the meta-reinforcement learning algorithm based on S2S neural network can quickly converge to the optimal state by only updating the gradient of S2S neural network parameters with a small sample set when a new signal environment appears.

9.
Sensors (Basel) ; 23(4)2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36850454

RESUMEN

In order to solve the problem of the quantification of detection signals in the magnetic flux leakage (MFL) of defective in-service oil and gas pipelines, a non-uniform magnetic charge model was established based on magnetic effects. The distribution patterns of magnetic charges under different stresses were analyzed. The influences of the elastic load and plastic deformation on the characteristic values of MFL signals were quantitatively assessed. The experimental results showed that the magnetic charge density was large at the edges of the defect and small at the center, and approximately decreased linearly with increasing stress. The eigenvalues of the axial and radial components of the MFL signals were compared, and it was found that the eigenvalues of the radial component exhibited a larger decline rate and were more sensitive to stress. With the increase in the plastic deformation, the characteristic values of the MFL signals initially decreased and then increased, and there was an inflection point. The location of the inflection point was associated with the magnetostriction coefficient. Compared with the uniform magnetic charge model, the accuracy of the axial and radial components of the MFL signals in the elastic stage of the improved magnetic charge model rose by 17% and 16%, respectively. The accuracy of the axial and radial components of the MFL signals were elevated by 9.15% and 9%, respectively, in the plastic stage.

10.
Molecules ; 28(23)2023 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-38067643

RESUMEN

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies.


Asunto(s)
Complejos de Coordinación , Fotoquimioterapia , Oxígeno Singlete/química , Fármacos Fotosensibilizantes/química , Iridio/química , Fotoquimioterapia/métodos , Complejos de Coordinación/química , Especies Reactivas de Oxígeno/química
11.
Angew Chem Int Ed Engl ; 62(36): e202304699, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37409373

RESUMEN

Developing new reactive pathway to activate inert C(sp3 )-H bonds for valuable oxygenated products remains a challenge. We prepared a series of triazine conjugated organic polymers to photoactivate C-H into aldehyde/ketone via O2 →H2 O2 →⋅OH→Cl⋅→Cl2 ⋅- . Experiment results showed Cl2 ⋅- could successively activate C(sp3 )-H more effectively than Cl⋅ to generate unstable dichlorinated intermediates, increasing the kinetic rate ratio of dichlorination to monochlorination by a factor of 2,000 and thus breaking traditional dichlorination kinetic constraints. These active intermediates were hydrolyzed into aldehydes or ketones easily, when compared with typical stable dichlorinated complexes, avoiding chlorinated by-product generation. Moreover, an integrated two-phase system in an acid solution strengthened the Cl2 ⋅- mediated process and inhibited product overoxidation, where the conversion rate of toluene reached 16.94 mmol/g/h and the selectivity of benzaldehyde was 99.5 %. This work presents a facile and efficient approach for selective conversion of inert C(sp3 )-H bonds using Cl2 ⋅- .

12.
Angew Chem Int Ed Engl ; 62(2): e202215906, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36374215

RESUMEN

Biological ion channels penetrated through cell membrane form unique transport pathways for selective ionic conductance. Replicating the success of ion selectivity with mixed matrix membranes (MMMs) will enable new separation technologies but remains challenging. Herein, we report a soft substrate-assisted solution casting method to develop MMMs with penetrating subnanochannels for selective metal ion conduction. The MMMs are composed of penetrating Prussian white (PW) microcubes with subnanochannels in dense polyimide (PI) matrices, achieving selective monovalent metal ion conduction. The ion selectivity of K+ /Mg2+ is up to 14.0, and the ion conductance of K+ can reach 45.5 µS with the testing diameter of 5 mm, which can be further improved by increasing the testing area. Given the diversity of nanoporous materials and polymer matrices, we expect that the MMMs with penetrating subnanochannels could be developed into a versatile nanofluidic platform for various emerging applications.


Asunto(s)
Metales , Nanoporos , Membrana Celular , Iones , Polímeros
13.
J Cell Mol Med ; 26(8): 2205-2217, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35166018

RESUMEN

The phytoalexin resveratrol exhibits anti-tumour activity in many types of cancer. In this study, we showed that resveratrol suppressed the survival of gastric tumour cells both in vivo and in vitro. Resveratrol promoted apoptosis, autophagy and endoplasmic reticulum (ER) stress in a dose-dependent manner. RNA-seq analysis showed that multiple cell death signalling pathways were activated after resveratrol treatment, while the use of ER stress activators (tunicamycin and thapsigargin) in combinatorial with resveratrol led to further inhibition of cancer cell survival. Results also showed that resveratrol altered the expression of several long non-coding RNAs (lncRNAs), including MEG3, PTTG3P, GAS5, BISPR, MALAT1 and H19. Knockdown of H19 in resveratrol-treated cells further enhanced the effects of resveratrol on apoptosis, ER stress and cell cycle S-phase arrest. Furthermore, the migratory ability of resveratrol-treated cells was dramatically decreased after H19 knockdown. In conclusion, resveratrol inhibited cancer cell survival, while knockdown of lncRNA H19 resulted in increased sensitivity to resveratrol therapy.


Asunto(s)
Neoplasias , ARN Largo no Codificante , Resveratrol , Apoptosis , Línea Celular Tumoral , Proliferación Celular/genética , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Resveratrol/farmacología
14.
Small ; 18(36): e2106824, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35060321

RESUMEN

The development of programmable functional biomaterials makes 4D printing add a new dimension, time (t), based on 3D structures (x, y, z), therefore, 4D printed constructs could transform their morphology or function over time in response to environmental stimuli. Nowadays, highly efficient bone defect repair remains challenging in clinics. Combining programmable biomaterials, living cells, and bioactive factors, 4D bioprinting provides greater potential for constructing dynamic, personalized, and precise bone tissue engineering scaffolds by complex structure formation and functional maturation. Therefore, 4D bioprinting has been regarded as the next generation of bone repair technology. This review focuses on 4D printing and its advantages in orthopedics. The applications of different smart biomaterials and 4D printing strategies are briefly introduced. Furthermore, one summarizes the recent advancements of 4D printing in bone tissue engineering, uncovering the addressed and unaddressed medical requirements. In addition, current challenges and future perspectives are further discussed, which will offer more inspiration about the clinical transformation of this emerging 4D bioprinting technology in bone regeneration.


Asunto(s)
Bioimpresión , Ortopedia , Materiales Biocompatibles/química , Impresión Tridimensional , Ingeniería de Tejidos/métodos
15.
J Nanobiotechnology ; 20(1): 147, 2022 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-35305648

RESUMEN

Clinical work and research on diabetic wound repair remain challenging globally. Although various conventional wound dressings have been continuously developed, the efficacy is unsatisfactory. The effect of drug delivery is limited by the depth of penetration. The sustained release of biomolecules from biological wound dressings is a promising treatment approach to wound healing. An assortment of cell-derived exosomes (exos) have been proved to be instrumental in tissue regeneration, and researchers are dedicated to developing biomolecules carriers with unique properties. Herein, we reported a methacrylate gelatin (GelMA) microneedles (MNs) patch to achieve transdermal and controlled release of exos and tazarotene. Our MNs patch comprising GelMA/PEGDA hydrogel has distinctive biological features that maintain the biological activity of exos and drugs in vitro. Additionally, its unique physical structure prevents it from being tightly attached to the skin of the wound, it promotes cell migration, angiogenesis by slowly releasing exos and tazarotene in the deep layer of the skin. The full-thickness cutaneous wound on a diabetic mouse model was carried out to demonstrate the therapeutic effects of GelMA/PEGDA@T + exos MNs patch. As a result, our GelMA/PEGDA@T + exos MNs patch presents a potentially valuable method for repairing diabetic wound in clinical applications.


Asunto(s)
Diabetes Mellitus , Exosomas , Animales , Gelatina/farmacología , Ratones , Ácidos Nicotínicos , Cicatrización de Heridas
16.
Molecules ; 27(6)2022 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-35335173

RESUMEN

The distribution of pharmatically important alkaloids gelsemine, koumine, and gelsenicine in Gelsemium elegans tissues is a hot topic attracting research attention. Regretfully, the in planta visual distribution details of these alkaloids are far from clear although several researches reported the alkaloid quantification in G. elegans by LC-MS/MS. In this study, mass imaging spectrometry (MSI) was employed to visualize the in situ visualization of gelsemine, koumine, and gelsenicine in different organs and tissues of G. elegans at different growth stages, and the relative quantification of three alkaloids were performed according to the image brightness intensities captured by the desorption electrospray ionization MSI (DESI-MSI). The results indicated that these alkaloids were mainly accumulated in pith region and gradually decreased from pith to epidermis. Interestingly, three alkaloids were found to be present in higher abundance in the leaf vein. Along with the growth and development, the accumulation of these alkaloids was gradually increased in root and stem. Moreover, we employed LC-MS/MS to quantify three alkaloids and further validated the in situ distributions. The content of koumine reached 249.2 µg/g in mature roots, 272.0 µg/g in mature leaves, and 149.1 µg/g in mature stems, respectively, which is significantly higher than that of gelsemine and gelsenicine in the same organ. This study provided an accurately in situ visualization of gelsemine, koumine, and gelsenicine in G. elegans, and would be helpful for understanding their accumulation in plant and guiding application.


Asunto(s)
Alcaloides , Espectrometría de Masas en Tándem , Cromatografía Liquida , Alcaloides Indólicos
17.
J Cell Mol Med ; 25(15): 7135-7145, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34164906

RESUMEN

In recent years, the repurposing of conventional and chemotherapeutic drugs is recognized as an alternative strategy for health care. The main purpose of this study is to strengthen the application of non-oncological drug metformin on breast cancer treatment in the perspective of epigenetics. In the present study, metformin was found to inhibit cell proliferation, promote apoptosis and induce cell cycle arrest in breast cancer cells at a dose-dependent manner. In addition, metformin treatment elevated acH3K9 abundance and decreased acH3K18 level. The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment. In metformin-treated cells, MALAT1 knock-down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression. The expression of Beclin1, VDAC1, LC3-II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock-down. The reduced phosphorylation of c-Myc was further decreased in the metformin-treated cells in combination with MALAT1 knock-down than metformin treatment alone. Taken together, these results provide a promising repurposed strategy for metformin on cancer treatment by modulating epigenetic modifiers.


Asunto(s)
Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Hipoglucemiantes/farmacología , Metformina/farmacología , ARN Largo no Codificante/metabolismo , Apoptosis/efectos de los fármacos , Beclina-1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Chaperón BiP del Retículo Endoplásmico/metabolismo , Femenino , Humanos , Células MCF-7 , Proteínas Asociadas a Microtúbulos/metabolismo , ARN Largo no Codificante/genética , Factor de Transcripción CHOP/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/metabolismo
18.
Molecules ; 26(11)2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34070428

RESUMEN

Magnetic MXene composite Fe3O4@Ti3C2 was successfully prepared and employed as 17α-ethinylestradiol (EE2) adsorbent from water solution. The response surface methodology was employed to investigate the interactive effects of adsorption parameters (adsorption time, pH of the solution, initial concentration, and the adsorbent dose) and optimize these parameters for obtaining maximum adsorption efficiency of EE2. The significance of independent variables and their interactions were tested by the analysis of variance (ANOVA) and t-test statistics. Optimization of the process variables for maximum adsorption of EE2 by Fe3O4@Ti3C2 was performed using the quadratic model. The model predicted maximum adsorption of 97.08% under the optimum conditions of the independent variables (adsorption time 6.7 h, pH of the solution 6.4, initial EE2 concentration 0.98 mg L-1, and the adsorbent dose 88.9 mg L-1) was very close to the experimental value (95.34%). pH showed the highest level of significance with the percent contribution (63.86%) as compared to other factors. The interactive influences of pH and initial concentration on EE2 adsorption efficiency were significant (p < 0.05). The goodness of fit of the model was checked by the coefficient of determination (R2) between the experimental and predicted values of the response variable. The response surface methodology successfully reflects the impact of various factors and optimized the process variables for EE2 adsorption. The kinetic adsorption data for EE2 fitted well with a pseudo-second-order model, while the equilibrium data followed Langmuir isotherms. Thermodynamic analysis indicated that the adsorption was a spontaneous and endothermic process. Therefore, Fe3O4@Ti3C2 composite present the outstanding capacity to be employed in the remediation of EE2 contaminated wastewaters.


Asunto(s)
Etinilestradiol/química , Magnetismo , Termodinámica , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Adsorción , Etinilestradiol/aislamiento & purificación , Cinética , Nanopartículas del Metal/química , Aguas Residuales/química , Difracción de Rayos X
19.
Comput Biol Med ; 173: 108350, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38555705

RESUMEN

Cell protrusions play an important role in a variety of cell physiological processes. In this paper, we propose a convex-hull based method, combined with manifold projections, to detect cell protrusions. A convex hull is generated based on the cell surface. We consider the cell surface and the boundary of its convex hull as two manifolds, which are diffeomorphic, and define a depth function based on the distance between the cell surface and its convex hull boundary. The extreme points of the depth function represent the positions of cell protrusions. To find the extreme points easily, we project the points on the cell surface onto the boundary of the convex hull and expand them in spherical polar coordinates. We conducted experiments on three types of cell protrusions. The proposed method achieved the average precision of 98.9%, 95.6%, and 94.7% on blebs, filopodia, and lamellipodia, respectively. Experiments on three datasets show that the proposed method has a robust performance.

20.
Nat Protoc ; 19(3): 831-895, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38135744

RESUMEN

Advances in spatial omics technologies have improved the understanding of cellular organization in tissues, leading to the generation of complex and heterogeneous data and prompting the development of specialized tools for managing, loading and visualizing spatial omics data. The Spatial Omics Database (SODB) was established to offer a unified format for data storage and interactive visualization modules. Here we detail the use of Pysodb, a Python-based tool designed to enable the efficient exploration and loading of spatial datasets from SODB within a Python environment. We present seven case studies using Pysodb, detailing the interaction with various computational methods, ensuring reproducibility of experimental data and facilitating the integration of new data and alternative applications in SODB. The approach offers a reference for method developers by outlining label and metadata availability in representative spatial data that can be loaded by Pysodb. The tool is supplemented by a website ( https://protocols-pysodb.readthedocs.io/ ) with detailed information for benchmarking analysis, and allows method developers to focus on computational models by facilitating data processing. This protocol is designed for researchers with limited experience in computational biology. Depending on the dataset complexity, the protocol typically requires ~12 h to complete.


Asunto(s)
Biología Computacional , Programas Informáticos , Reproducibilidad de los Resultados , Biología Computacional/métodos , Bases de Datos Factuales , Análisis de Datos
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