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1.
bioRxiv ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38895479

RESUMEN

Epigenomic mechanisms are critically involved in mediation of genetic and environmental factors that underlie cancer development. Histone modifications represent highly informative epigenomic marks that reveal activation and repression of gene activities and dysregulation of transcriptional control due to tumorigenesis. Here, we present a comprehensive epigenomic and transcriptomic mapping of 18 tumor and 20 non-neoplastic tissues from non-small cell lung adenocarcinoma patients. Our profiling covers 5 histone marks including activating (H3K4me3, H3K4me1, and H3K27ac) and repressive (H3K27me3 and H3K9me3) marks and the transcriptome using only 20 mg of tissue per sample, enabled by low-input omic technologies. Using advanced integrative bioinformatic analysis, we uncovered cancer-driving signaling cascade networks, changes in 3D genome modularity, and differential expression and functionalities of transcription factors and noncoding RNAs. Many of these identified genes and regulatory molecules showed no significant change in their expression or a single epigenomic modality, emphasizing the power of integrative multimodal and multiomic analysis using patient samples.

2.
Science ; 384(6701): 1203-1212, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38870306

RESUMEN

Radiative cooling textiles hold promise for achieving personal thermal comfort under increasing global temperature. However, urban areas have heat island effects that largely diminish the effectiveness of cooling textiles as wearable fabrics because they absorb emitted radiation from the ground and nearby buildings. We developed a mid-infrared spectrally selective hierarchical fabric (SSHF) with emissivity greatly dominant in the atmospheric transmission window through molecular design, minimizing the net heat gain from the surroundings. The SSHF features a high solar spectrum reflectivity of 0.97 owing to strong Mie scattering from the nano-micro hybrid fibrous structure. The SSHF is 2.3°C cooler than a solar-reflecting broadband emitter when placed vertically in simulated outdoor urban scenarios during the day and also has excellent wearable properties.

3.
Environ Sci Pollut Res Int ; 31(25): 37848-37861, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38795294

RESUMEN

Arsenic (As) is one extremely hazardous and carcinogenic metalloid element. Due to mining, metal smelting, and other human activities, the pollution of water (especially groundwater) and soil caused by As is increasingly serious, which badly threatens the environment and human health. In this study, a zeolite imidazolate framework (ZIF-8) was synthesized at room temperature and employed as an adsorbent to facilitate the adsorption of As(III) and As(V) from the solution. The successful synthesis of ZIF-8 was demonstrated by X-ray diffraction (XRD), and scanning electron microscopy (SEM) revealed that its particle size was approximately 80 nm. The adsorption kinetics, adsorption isotherm, solution pH, dose, coexisting ions, and the synonymous elements antimony (Sb) were conducted to study the adsorption of As by ZIF-8 nanoparticles. The maximum saturation adsorption capacity was determined to be 101.47 mg/g and 81.40 mg/g for As(III), and As(V) at initial pH = 7.0, respectively. Apparently, ZIF-8 had a good removal effect on As, and it still maintained a good performance after four cycles. The coexisting ions PO43- and CO32- inhibited the adsorption of both As(III) and As(V). ZIF-8 performed well in removing both As and Sb simultaneously, although the presence of Sb hindered the adsorption of both As(III) and As(V). Both FTIR and XPS indicated the adsorption mechanism of As on ZIF-8: ZIF-8 generates a large amount of Zn-OH on the surface through hydrolysis and partial fracture of Zn-N, both of which form surface complexes with As.


Asunto(s)
Arsénico , Contaminantes Químicos del Agua , Zeolitas , Adsorción , Zeolitas/química , Arsénico/química , Contaminantes Químicos del Agua/química , Imidazoles/química , Cinética , Purificación del Agua/métodos , Difracción de Rayos X , Concentración de Iones de Hidrógeno
4.
Commun Biol ; 7(1): 551, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720110

RESUMEN

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies.


Asunto(s)
Neoplasias Colorrectales , Epigenoma , Infecciones por Fusobacterium , Fusobacterium nucleatum , Oxígeno , Transcriptoma , Humanos , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/fisiología , Fusobacterium nucleatum/patogenicidad , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/microbiología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Células HCT116 , Infecciones por Fusobacterium/genética , Infecciones por Fusobacterium/microbiología , Infecciones por Fusobacterium/metabolismo , Oxígeno/metabolismo , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica
5.
Orthop Surg ; 16(5): 1089-1100, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38561949

RESUMEN

OBJECTIVE: The risk of osteochondral fracture (OCF) after patellar dislocation has been shown to be related to patellofemoral anatomy, but its relationship to patellar morphology remains unknown. The aim of this study was to investigate the associations between patellar morphology and the risk of OCF after patellar dislocation. METHODS: A total of 140 patients with patellar dislocation between January 2018 and June 2023 were enrolled in this study and divided into two groups. Sixty-five patellar dislocation patients with OCF were included in the OCF group, while 75 patellar dislocation patients without OCF were included in the non-OCF group. Computed tomography was used to compare measurements of patellar morphology including Wiberg classification, patellar width and thickness, Wiberg angle, Wiberg index, facet ratio, lateral patellar facet angle, and patellar tilt angle. A logistic regression model was performed to evaluate the correlations between patellar morphology and the risk of OCF after patellar dislocation. Receiver operating characteristic curves were used to calculate the area under the curve (AUC) and determine the diagnostic values of patellar morphology for OCF after patellar dislocation. Subgroup analyses for gender and age were conducted to compare the differences in patellar morphology of PD patients. RESULTS: Wiberg angle was significantly lower in the OCF group (p = 0.017), while Wiberg index (p = 0.002) and facet ratio (p = 0.023) were significantly higher in the OCF group. According to the results of logistic regression analysis, Wiberg angle (odds ratio [OR] = 0.96, p = 0.022) and Wiberg index (OR = 1.105, p = 0.032) were the final relevant factors for the occurrence of OCF after patellar dislocation. The AUC was 0.622 (95% confidence interval [CI]: 0.529-0.714) for Wiberg angle, 0.65 (95% CI: 0.558-0.742) for Wiberg index, and 0.702 (95% CI: 0.615-0.788) for the combination of Wiberg angle plus Wiberg index. CONCLUSION: Wiberg angle and Wiberg index were independent risk factors for the occurrence of osteochondral fracture after patellar dislocation. Moreover, Wiberg angle, Wiberg index, and the combination of Wiberg angle plus Wiberg index had good predictive diagnostic value for the occurrence of OCF after patellar dislocation.


Asunto(s)
Rótula , Luxación de la Rótula , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Luxación de la Rótula/diagnóstico por imagen , Luxación de la Rótula/etiología , Estudios Transversales , Rótula/diagnóstico por imagen , Rótula/lesiones , Adulto , Adulto Joven , Factores de Riesgo , Adolescente , Fracturas Óseas/diagnóstico por imagen , Estudios Retrospectivos
6.
J Ethnopharmacol ; 330: 118232, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38670407

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Arbutin is a naturally occurring glucoside extracted from plants, known for its antioxidant and tyrosinase inhibiting properties. It is widely used in cosmetic and pharmaceutical industries. With in-depth study of arbutin, its application in disease treatment is expanding, presenting promising development prospects. However, reports on the metabolic stability, plasma protein binding rate, and pharmacokinetic properties of arbutin are scarce. AIM OF THE STUDY: The aim of this study is to enrich the data of metabolic stability and pharmacokinetics of arbutin through the early pre-clinical evaluation, thereby providing some experimental basis for advancing arbutin into clinical research. MATERIALS AND METHODS: We developed an efficient and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determining arbutin in plasma. We investigated the metabolic and pharmacokinetic properties of arbutin through in vitro metabolism assay, cytochrome enzymes P450 (CYP450) inhibition studies, plasma protein binding rate analysis, Caco-2 cell permeability tests, and rat pharmacokinetics to understand its in vivo performance. RESULTS: In vitro studies show that arbutin is stable, albeit with some species differences. It exhibits low plasma protein binding (35.35 ± 11.03% âˆ¼ 40.25 ± 2.47%), low lipophilicity, low permeability, short half-life (0.42 ± 0.30 h) and high oral bioavailability (65 ± 11.6%). Arbutin is primarily found in the liver and kidneys and is eliminated in the urine. It does not significantly inhibit CYP450 up to 10 µM, suggesting a low potential for drug interactions. Futhermore, preliminary toxicological experiments indicate arbutin's safety, supporting its potential as a therapeutic agent. CONCLUSION: This study provides a comprehensive analysis the drug metabolism and pharmacokinetics (DMPK) of arbutin, enriching our understanding of its metabolism stability and pharmacokinetics properties, It establishes a foundation for further structural optimization, pharmacological studies, and the clinical development of arbutin.


Asunto(s)
Arbutina , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Arbutina/farmacocinética , Arbutina/farmacología , Espectrometría de Masas en Tándem/métodos , Animales , Humanos , Células CACO-2 , Masculino , Cromatografía Liquida/métodos , Ratas , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Unión Proteica , Sistema Enzimático del Citocromo P-450/metabolismo , Productos Biológicos/farmacocinética , Productos Biológicos/farmacología , Productos Biológicos/química , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Inhibidores Enzimáticos del Citocromo P-450/farmacocinética , Cromatografía Líquida con Espectrometría de Masas
7.
Cell Rep Methods ; 4(3): 100738, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38508188

RESUMEN

Spatially resolved epigenomic profiling is critical for understanding biology in the mammalian brain. Single-cell spatial epigenomic assays were developed recently for this purpose, but they remain costly and labor intensive for examining brain tissues across substantial dimensions and surveying a collection of brain samples. Here, we demonstrate an approach, epigenomic tomography, that maps spatial epigenomes of mouse brain at the scale of centimeters. We individually profiled neuronal and glial fractions of mouse neocortex slices with 0.5 mm thickness. Tri-methylation of histone 3 at lysine 27 (H3K27me3) or acetylation of histone 3 at lysine 27 (H3K27ac) features across these slices were grouped into clusters based on their spatial variation patterns to form epigenomic brain maps. As a proof of principle, our approach reveals striking dynamics in the frontal cortex due to kainic-acid-induced seizure, linked with transmembrane ion transporters, exocytosis of synaptic vesicles, and secretion of neurotransmitters. Epigenomic tomography provides a powerful and cost-effective tool for characterizing brain disorders based on the spatial epigenome.


Asunto(s)
Cromatina , Neocórtex , Ratones , Animales , Histonas/genética , Epigenómica/métodos , Lisina , Neocórtex/metabolismo , Mamíferos/metabolismo
8.
J Clin Invest ; 134(7)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300705

RESUMEN

Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor located in the sarcoplasmic reticulum (SR) of skeletal muscle, where it is best known for its role in store-operated Ca2+ entry (SOCE). Genetic syndromes resulting from STIM1 mutations are recognized as a cause of muscle weakness and atrophy. Here, we focused on a gain-of-function mutation that occurs in humans and mice (STIM1+/D84G mice), in which muscles exhibited constitutive SOCE. Unexpectedly, this constitutive SOCE did not affect global Ca2+ transients, SR Ca2+ content, or excitation-contraction coupling (ECC) and was therefore unlikely to underlie the reduced muscle mass and weakness observed in these mice. Instead, we demonstrate that the presence of D84G STIM1 in the nuclear envelope of STIM1+/D84G muscle disrupted nuclear-cytosolic coupling, causing severe derangement in nuclear architecture, DNA damage, and altered lamina A-associated gene expression. Functionally, we found that D84G STIM1 reduced the transfer of Ca2+ from the cytosol to the nucleus in myoblasts, resulting in a reduction of [Ca2+]N. Taken together, we propose a novel role for STIM1 in the nuclear envelope that links Ca2+ signaling to nuclear stability in skeletal muscle.


Asunto(s)
Debilidad Muscular , Membrana Nuclear , Molécula de Interacción Estromal 1 , Animales , Humanos , Ratones , Calcio/metabolismo , Señalización del Calcio , Debilidad Muscular/genética , Debilidad Muscular/metabolismo , Músculo Esquelético/metabolismo , Mutación , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Membrana Nuclear/genética , Membrana Nuclear/metabolismo , Proteína ORAI1/genética , Molécula de Interacción Estromal 1/genética , Molécula de Interacción Estromal 1/metabolismo
9.
ACS Nano ; 18(1): 858-873, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38108289

RESUMEN

Colloidal semiconductor nanocrystals are an important class of materials which have many desirable optoelectronic properties. In their bulk phases, gallium- and aluminum-containing III-V materials such as GaAs, GaP, and Al1-xGaxAs represent some of the most technologically important semiconductors. However, their colloidal synthesis by traditional methods is difficult due to the high temperatures needed to crystallize these highly covalent materials and the extreme reactivity of Ga- and Al- precursors toward organic solvents at such high temperatures. A recently developed paradigm shift in the synthesis of these materials is to use molten inorganic salts as solvents to prepare Ga- containing III-V colloidal nanocrystals by cation exchange of the corresponding indium pnictide (InPn) colloidal nanocrystals. There have been several successful applications of molten salt solvents to prepare III-phosphide colloidal nanocrystals. However, little is known about the nature of these reaction environments at the relevant reaction conditions and synthesis of III-arsenide colloidal nanocrystals remains challenging. Herein we report a detailed study on cation exchange of InPn nanocrystals using nominally Lewis basic molten salt solvents with added gallium halides. Surprisingly, these salt systems phase separate into two immiscible phases, and the nanocrystals preferentially segregate to one of the phases. Using a suite of in situ spectroscopy tools, we identify the phase the nanocrystals segregate to as Lewis neutral alkali tetrahalogallate molten salts. We apply in situ high-temperature Raman spectroscopy to identify the chemical species present in several molten salt compositions at experimentally relevant reaction conditions to elucidate a molecular basis for the reactivity observed. We then employ Lewis neutral KGaI4 molten salts to prepare high-quality In1-xGaxAs and In1-xGaxP nanocrystals and demonstrate that deviation from Lewis neutral conditions accelerate nanocrystal decomposition in the case of III-arsenide materials. Further, we expand to KAlI4-based molten salts to prepare In1-x-yGaxAlyAs nanocrystals which represent an example of solution-synthesized quaternary III-V nanocrystals. These insights provide a molecular basis for the rational development of molten salt solvents, thus allowing the preparation of a diverse array of multicomponent III-V colloidal nanocrystals.

10.
Nat Commun ; 14(1): 4672, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37537185

RESUMEN

The genome-wide DNA methylation profile, or DNA methylome, is a critical component of the overall epigenomic landscape that modulates gene activities and cell fate. Single-cell DNA methylomic studies offer unprecedented resolution for detecting and profiling cell subsets based on methylomic features. However, existing single-cell methylomic technologies are based on use of tubes or well plates and these platforms are not easily scalable for handling a large number of single cells. Here we demonstrate a droplet-based microfluidic technology, Drop-BS, to construct single-cell bisulfite sequencing libraries for DNA methylome profiling. Drop-BS takes advantage of the ultrahigh throughput offered by droplet microfluidics to prepare bisulfite sequencing libraries of up to 10,000 single cells within 2 days. We apply the technology to profile mixed cell lines, mouse and human brain tissues to reveal cell type heterogeneity. Drop-BS offers a promising solution for single-cell methylomic studies requiring examination of a large cell population.


Asunto(s)
Metilación de ADN , Epigenoma , Humanos , Animales , Ratones , Análisis de Secuencia de ADN , Sulfitos , Secuenciación de Nucleótidos de Alto Rendimiento
11.
Nat Chem ; 15(12): 1722-1729, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37537297

RESUMEN

Two-dimensional (2D) transition-metal carbides and nitrides (MXenes) combine the electronic and mechanical properties of 2D inorganic crystals with chemically modifiable surfaces, which provides an ideal platform for both fundamental and applied studies of interfaces. Good progress has been achieved in the functionalization of MXenes with small inorganic ligands, but relatively little work has been reported on the covalent bonding of various organic groups to MXene surfaces. Here we synthesize a family of hybrid MXenes (h-MXenes) that incorporate amido- and imido-bonding between organic and inorganic parts by reacting halogen-terminated MXenes with deprotonated organic amines. The resulting hybrid structures unite tailorability of organic molecules with electronic connectivity and other properties of inorganic 2D materials. Describing the structure of h-MXene necessitates the integration of concepts from coordination chemistry, self-assembled monolayers and surface science. The optical properties of h-MXenes reveal coherent coupling between the organic and inorganic constituents. h-MXenes also exhibit superior stability against hydrolysis.

12.
Elife ; 122023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37589705

RESUMEN

N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239-580 of METTL3). We find that METTL3a is required for the METTL3-WTAP interaction, RNA m6A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3-METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m6A sequencing data shows that depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of TMEM127 expression. Moreover, we find that METTL3 cleavage is mediated by proteasome in an mTOR-dependent manner, revealing positive regulatory feedback between METTL3a and mTOR signaling. Our findings reveal METTL3a as an important component of MTC, and suggest the METTL3a-mTOR axis as a potential therapeutic target for breast cancer.


Asunto(s)
Neoplasias de la Mama , Proteínas de Ciclo Celular , Metiltransferasas , Factores de Empalme de ARN , Humanos , Proteínas de Ciclo Celular/genética , Transformación Celular Neoplásica , Citoplasma , Metiltransferasas/genética , ARN , Factores de Empalme de ARN/genética , Neoplasias de la Mama/patología , Progresión de la Enfermedad
13.
Mol Biomed ; 4(1): 17, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37273004

RESUMEN

The tumor microenvironment (TME) is crucial to neoplastic processes, fostering proliferation, angiogenesis and metastasis. Epigenetic regulations, primarily including DNA and RNA methylation, histone modification and non-coding RNA, have been generally recognized as an essential feature of tumor malignancy, exceedingly contributing to the dysregulation of the core gene expression in neoplastic cells, bringing about the evasion of immunosurveillance by influencing the immune cells in TME. Recently, compelling evidence have highlighted that clinical therapeutic approaches based on epigenetic machinery modulate carcinogenesis through targeting TME components, including normalizing cells' phenotype, suppressing cells' neovascularization and repressing the immunosuppressive components in TME. Therefore, TME components have been nominated as a promising target for epigenetic drugs in clinical cancer management. This review focuses on the mechanisms of epigenetic modifications occurring to the pivotal TME components including the stroma, immune and myeloid cells in various tumors reported in the last five years, concludes the tight correlation between TME reprogramming and tumor progression and immunosuppression, summarizes the current advances in cancer clinical treatments and potential therapeutic targets with reference to epigenetic drugs. Finally, we summarize some of the restrictions in the field of cancer research at the moment, further discuss several interesting epigenetic gene targets with potential strategies to boost antitumor immunity.

14.
bioRxiv ; 2023 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-37293095

RESUMEN

Genome-wide DNA methylation profile, or DNA methylome, is a critical component of the overall epigenomic landscape that modulates gene activities and cell fate. Single-cell DNA methylomic studies offer unprecedented resolution for detecting and profiling cell subsets based on methylomic features. However, existing single-cell methylomic technologies are all based on use of tubes or well plates and these platforms are not easily scalable for handling a large number of single cells. Here we demonstrate a droplet-based microfluidic technology, Drop-BS, to construct single-cell bisulfite sequencing libraries for DNA methylome profiling. Drop-BS takes advantage of the ultrahigh throughput offered by droplet microfluidics to prepare bisulfite sequencing libraries of up to 10,000 single cells within 2 d. We applied the technology to profile mixed cell lines, mouse and human brain tissues to reveal cell type heterogeneity. Drop-BS will pave the way for single-cell methylomic studies requiring examination of a large cell population.

15.
Acta bioeth ; 29(1): 9-16, jun. 2023.
Artículo en Inglés | LILACS | ID: biblio-1439069

RESUMEN

In recent years, the vigorous development of clinical researches carried out by medical schools is inseparable from the effective participation of medical students. However, as the number and categories of clinical research projects that medical students participate in increase, medical ethics related issues gradually occur. This article sorts out the ethical issues that arose in clinical researches, in which medical students participated, analyzes the underlying causes, and proposes solutions for the above-mentioned ethical issues, aiming to provide reference for medical ethics education and research project management for medical schools.


La participación efectiva de los estudiantes de medicina ha contribuido en gran medida al desarrollo exitoso de la investigación clínica en las escuelas de medicina de China en los últimos años. Sin embargo, con el creciente número y tipos de proyectos de investigación clínica en los que participan estudiantes de medicina, las cuestiones éticas se exponen gradualmente. Este trabajo enumera las cuestiones éticas que han surgido en la participación de los estudiantes de medicina en la investigación clínica en los últimos años, analiza las causas subyacentes y propone soluciones a las cuestiones éticas mencionadas anteriormente, con el objetivo de proporcionar referencia para la enseñanza de la ética médica y la gestión de proyectos de investigación para las escuelas de medicina.


A participação efetiva dos estudantes de medicina tem contribuído muito para o próspero desenvolvimento da pesquisa clínica nas escolas médicas da China nos últimos anos. No entanto, com o aumento do número e tipos de projetos de pesquisa clínica dos quais os estudantes de medicina participam, questões relacionadas à ética e à alfabetização são gradualmente expostas. Este artigo lista as questões éticas que surgiram na participação de estudantes de medicina em pesquisas clínicas nos últimos anos, analisa as causas subjacentes e propõe soluções para as questões éticas acima mencionadas, com o objetivo de fornecer referência para o ensino de ética médica e gestão de projetos de pesquisa para escolas médicas.


Asunto(s)
Humanos , Masculino , Femenino
16.
bioRxiv ; 2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37205564

RESUMEN

Stromal interaction molecule 1 (STIM1) is a Ca 2+ sensor located in the sarcoplasmic reticulum (SR) of skeletal muscle where it is best known for its role in store operated Ca 2+ entry (SOCE). Genetic syndromes resulting from STIM1 mutations are recognized as a cause of muscle weakness and atrophy. Here, we focus on a gain of function mutation that occurs in humans and mice (STIM1 +/D84G mice) where muscles exhibit constitutive SOCE. Unexpectedly, this constitutive SOCE did not affect global Ca 2+ transients, SR Ca 2+ content or excitation contraction coupling (ECC) and was therefore unlikely to underlie the reduced muscle mass and weakness observed in these mice. Instead, we demonstrate that the presence of D84G STIM1 in the nuclear envelope of STIM1 +/D84G muscle disrupts nuclear-cytosolic coupling causing severe derangement in nuclear architecture, DNA damage, and altered lamina A associated gene expression. Functionally, we found D84G STIM1 reduced the transfer of Ca 2+ from the cytosol to the nucleus in myoblasts resulting in a reduction of [Ca 2+ ] N . Taken together, we propose a novel role for STIM1 in the nuclear envelope that links Ca 2+ signaling to nuclear stability in skeletal muscle.

17.
Neurosci Lett ; 809: 137307, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37211325

RESUMEN

The demethylase JmjC structural domain-containing protein 8 (JMJD8) has been demonstrated to be involved in cellular inflammatory responses. Neuropathic pain (NP) is a chronic pain, and it is unclear whether JMJD8 is involved in the regulation of NP. Using a chronic constriction injury (CCI) mouse model of NP, we investigated the expression levels of JMJD8 during NP and the influences of JMJD8 on regulating pain sensitivity. We found that JMJD8 expression in the spinal dorsal horn was reduced after CCI. Immunohistochemistry showed that JMJD8 was colabeled with GFAP in naïve mice. Knockdown of JMJD8 in the spinal dorsal horn astrocytes induced pain behavior. Further study showed that overexpression of JMJD8 in the spinal dorsal horn astrocytes not only reversed pain behavior but also activated the spinal dorsal horn A1 astrocytes. These results suggest that JMJD8 may modulate pain sensitivity by affecting activated the spinal dorsal horn A1 astrocytes and may be a potential therapeutic target for NP.


Asunto(s)
Astrocitos , Neuralgia , Animales , Ratones , Astrocitos/metabolismo , Hiperalgesia/metabolismo , Neuralgia/metabolismo , Umbral del Dolor/fisiología , Médula Espinal/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo
18.
Neuromolecular Med ; 25(3): 375-387, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36971954

RESUMEN

The medial prefrontal cortex (mPFC) is critical for both the sensory and emotional/cognitive components of pain. However, the underlying mechanism remains largely unknown. Here, we examined changes in the transcriptomic profiles in the mPFC of mice with chronic pain using RNA sequencing (RNA-seq) technology. A mouse model of peripheral neuropathic pain was established via chronic constriction injury (CCI) of the sciatic nerve. CCI mice developed sustained mechanical allodynia and thermal hyperalgesia, as well as cognitive impairment four weeks after surgery. RNA-seq was conducted 4 weeks after CCI surgery. Compared with contral group, RNA-seq identified a total 309 and 222 differentially expressed genes (DEGs) in the ipsilateral and contralateral mPFC of CCI model mice, respectively. GO analysis indicated that the functions of these genes were mainly enriched in immune- and inflammation-related processes such as interferon-gamma production and cytokine secretion. KEGG analysis further showed the enrichment of genes involved in the neuroactive ligand-receptor interaction signaling pathway and Parkinson disease pathway that have been reported to be importantly involved in chronic neuralgia and cognitive dysfunction. Our study may provide insights into the possible mechanisms underlying neuropathic pain and pain-related comorbidities.


Asunto(s)
Hiperalgesia , Neuralgia , Ratones , Animales , Constricción , Hiperalgesia/genética , Neuralgia/genética , Perfilación de la Expresión Génica , Corteza Prefrontal/metabolismo
19.
ACS Nano ; 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36621974

RESUMEN

Group III nitrides are of great technological importance for electronic devices. These materials have been widely manufactured via high-temperature methods such as physical vapor transport (PVT), chemical vapor deposition (CVD), and hydride vapor phase epitaxy (HVPE). The preparation of group III nitrides by colloidal synthesis methods would provide significant advantages in the form of optical tunability via size and shape control and enable cost reductions through scalable solution-based device integration. Solution syntheses of III-nitride nanocrystals, however, have been scarce, and the quality of the synthesized products has been unsatisfactory for practical use. Here, we report that incorporating a molten salt phase in solution synthesis can provide a viable option for producing crystalline III-nitride nanomaterials. Crystalline GaN and AlN nanomaterials can be grown in a biphasic molten-salt/organic-solvent mixture under an ammonia atmosphere at moderate temperatures (less than 300 °C) and stabilized under ambient conditions by postsynthetic treatment with organic surface ligands. We suggest that microscopic reversibility of monomer attachment, which is essential for crystalline growth, can be achieved in molten salt during the nucleation and the growth of the III-nitride nanocrystals. We also show that increased ammonia pressure increases the size of the GaN nanocrystals produced. This work demonstrates that use of molten salt and high-pressure reactants significantly expands the chemical scope of solution synthesis of inorganic nanomaterials.

20.
Int J Periodontics Restorative Dent ; 43(1): e61­e71, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35612437

RESUMEN

This study evaluated the efficacy of trapezoidal coronally advanced flap (tCAF), envelope coronally advanced flap (eCAF), and coronally advanced tunnel flap (TUN) in treating gingival recession (GR) through a network meta-analysis. Eligible articles from the PubMed, Embase, and Cochrane Library databases published up to September 2020 were selected to identify randomized controlled trials (RCTs) on tCAF, eCAF, and TUN treatments. Sample size, treatment time, and outcome measures including complete root coverage (CRC), root coverage esthetic score (RES), and other data were extracted from the article, and integrated analysis was conducted. In total, 10 RCTs met the inclusion criteria, involving 310 patients. Direct meta-analysis showed no significant differences in CRC among the three surgical methods; A significant difference was seen for RES, with TUN worse than tCAF (weighted mean difference: -0.73; 95% CI: -1.44, -0.02; P = .045). The network meta-analysis showed no statistical significance in the cross-comparison of tCAF, eCAF, and TUN. However, eCAF had the most significant effect on improving CRC (SUCRA = 69.2) and RES (SUCRA = 85.0). eCAF has the best prognosis in the treatment of GR, followed by tCAF and TUN. This may influence the surgeon's treatment choice, as eCAF may be more effective in root coverage procedures.


Asunto(s)
Recesión Gingival , Humanos , Recesión Gingival/cirugía , Encía/cirugía , Resultado del Tratamiento , Metaanálisis en Red , Raíz del Diente/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Tejido Conectivo
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