Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 151
Filtrar
1.
Small ; : e2401194, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984765

RESUMO

High-sensitive uncooled mid-wave infrared (MWIR) photodetection with fast speed is highly desired for biomedical imaging, optical communication, and night vision technology. Low-dimensional materials with low dark current and broadband photoresponse hold great promise for use in MWIR detection. Here, this study reports a high-performance MWIR photodetector based on a titanium trisulfide (TiS3) nanoribbon. This device demonstrates an ultra-broadband photoresponse ranging from the visible spectrum to the MWIR spectrum (405-4275 nm). In the MWIR spectral range, the photodetector achieves competitive high photoresponsivity (R) of 21.1 A W-1, and an impressive specific detectivity (D*) of 5.9 × 1010 cmHz1/2 W-1 in ambient air. Remarkably, the photoresponse speed in the MWIR with τr = 1.3 ms and τd = 1.5 ms is realized which is much faster than the thermal time constant of 15 ms. These findings pave the way for highly sensitive, room-temperature MWIR photodetectors with exceptionally fast response speed.

2.
Neuro Oncol ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39021199

RESUMO

BACKGROUND: Glioblastoma due to recurrence is clinically challenging with 10-15months overall survival. Previously we showed therapy induced senescence (TIS) in glioblastoma reverses causing recurrence. Here, we aim to delineate TIS reversal mechanism for potential therapeutic intervention to prevent GBM recurrence. METHODS: Residual senescent (RS) and End of Residual Senescence (ERS) cells were captured from GBM patient-derived primary-cultures and cell lines mimicking clinical scenario. RNA-sequencing, transcript/protein validations, knock-down/inhibitor studies, ChIP RT-PCR, biochemical assays and IHCs were performed for mechanistics of TIS reversal. In vivo validations were conducted in GBM orthotopic mouse model. RESULTS: Transcriptome analysis showed co-expression of ER stress-UPR and senescence associated secretory phenotype (SASP) with TIS induction and reversal. Robust SASP production and secretion by RS cells could induce senescence, ROS, DNA damage and ER stress in paracrine fashion independent of radiation. Neutralization of most significantly enriched cytokine from RS-secretome IL1ß, suppressed SASP and delayed senescence reversal. Mechanistically, with SASP and massive protein accumulation in Endoplasmic reticulum, RS cells displayed stressed ER morphology, upregulated ER stress markers and PERK pathway activation via peIF2α-ATF4-CHOP which was spontaneously resolved in ERS. ChIP RT-PCR showed CHOP occupancy at CXCL8/IL8, CDKN1A/p21 and BCL2L1/BCLXL aiding survival. PERK knockdown/inhibition with GSK2606414 in combination with radiation led to sustained ER stress and senescence without SASP. PERKi in RS functioned as senolytic via apoptosis and prevented recurrence in vitro and in vivo ameliorating overall survival. CONCLUSION: We demonstrate that PERK mediated UPR regulates senescence reversal and its inhibition can be exploited as potential seno-therapeutic option in glioblastoma.

3.
Sci Rep ; 14(1): 15593, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971853

RESUMO

This research examines the psychometric characteristics and reliability of the 6-item turnover intention scale (TIS-6) by Bothma and Roodt (SA J Hum Resour Manag 11:a507, 2013) on a Hungarian sample. The internal validity of the TIS-6 was assessed using data from 269 Hungarian elderly care institution workers. Confirmatory factor analysis was performed to analyse the structural validity. Convergent and discriminant validity were examined with questions on job characteristics and using the Maslach Burnout Inventory and Effort-Reward Imbalance Scale. IBM SPSS 28.0 software was used for the statistical analysis, and the results were considered significant at p < 0.05. The internal consistency of the questionnaire's scale proved to be acceptable (α = 0.826). Convergent validity was confirmed by the relationships between the components of the questionnaire and burnout (rs = 0.512; p < 0.001; rs = 0.419; p < 0.001) and workplace stress (rs = 0.565; p < 0.001; rs = 0.310; p < 0.001). There were significant differences between the TIS-6 scores among the groups with different degrees of burnout (p < 0.001), which indicated adequate discriminant validity of the questionnaire. The structural validity of the questionnaire was acceptable, and the scale questions fit well. The Hungarian version of the TIS-6 scale is a valid and reliable tool for assessing turnover intention among elderly care institution workers in Hungary.


Assuntos
Esgotamento Profissional , Reorganização de Recursos Humanos , Psicometria , Humanos , Hungria , Feminino , Masculino , Inquéritos e Questionários , Psicometria/métodos , Esgotamento Profissional/psicologia , Pessoa de Meia-Idade , Adulto , Reprodutibilidade dos Testes , Satisfação no Emprego , Idoso , Intenção , Pessoal de Saúde/psicologia
4.
Front Chem ; 12: 1413850, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860237

RESUMO

Topological indices (TIs) have rich applications in various biological contexts, particularly in therapeutic strategies for cancer. Predicting the performance of compounds in the treatment of cancer is one such application, wherein TIs offer insights into the molecular structures and related properties of compounds. By examining, various compounds exhibit different degree-based TIs, analysts can pinpoint the treatments that are most efficient for specific types of cancer. This paper specifically delves into the topological indices (TIs) implementations in forecasting the biological and physical attributes of innovative compounds utilized in addressing cancer through therapeutic interventions. The analysis being conducted to derivatives of sulfonamides, namely, 4-[(2,4-dichlorophenylsulfonamido)methyl]cyclohexanecarboxylic acid (1), ethyl 4-[(naphthalene-2-sulfonamido)methyl]cyclohexanecarboxylate (2), ethyl 4-[(2,5-dichlorophenylsulfonamido)methyl]cyclohexanecarboxylate (3), 4-[(naphthalene-2-sulfonamido)methyl]cyclohexane-1-carboxylic acid (4) and (2S)-3-methyl-2-(naphthalene-1-sulfonamido)-butanoic acid (5), is performed by utilizing edge partitioning for the computation of degree-based graph descriptors. Subsequently, a linear regression-based model is established to forecast characteristics, like, melting point and formula weight in a quantitative structure-property relationship. The outcomes emphasize the effectiveness or capability of topological indices as a valuable asset for inventing and creating of compounds within the realm of cancer therapy.

5.
J Cytol ; 41(2): 96-104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779601

RESUMO

Background: The "International System of Reporting Serous Fluid Cytology (TIS)" together with cytomorphology promotes the use of ancillary techniques to resolve difficulties in reporting serous fluid cytology. Objective: To classify serous effusion fluid samples received at our department in line with "TIS", indicating the risk of malignancy (ROM), and directing appropriate usage of ancillary testing. Materials and Methods: Prospective study carried out from October 2021 to September 2022. The study included all pleural, ascitic, and pericardial fluid samples, reported according to 'TIS'. Flow cytometry and immunocytochemistry were ancillary methods utilized to assist in reporting. Cases with available history and convincing correlations didn't require further assessment. Results: A total of 1200 serous effusion samples were evaluated including 604 pleural, 591 ascitic, and 5 pericardial fluid samples. After categorization, there were 23 samples in non-diagnostic (ND, 1.9%), 575 in negative for malignancy (NFM, 47.91%), 44 in atypia of undetermined significance (AUS, 3.66%), 64 in suspicious for malignancy (SFM, 5.33%), and 494 in malignant category (MAL, 41.16%). Ancillary studies were beneficial in the recategorization of 26% (11/44) AUS cases, 29.6% (19/64) SFM cases, and it helped refine tumor characteristics in 35.42% (175/494) cases categorized as malignant. Final ROM calculated for each category: ND 25%, NFM 18.6%, AUS 66.6%, SFM 88%, and MAL 100%. Conclusion: Serous fluid is an easily obtainable sample that can provide opportunities for ancillary testing with clinical implications. In AUS and suspicious category although, diagnostic yield is increased however, a larger number of cases are required to obtain definite results.

6.
Cell Syst ; 15(4): 388-408.e4, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38636458

RESUMO

Genome-wide measurement of ribosome occupancy on mRNAs has enabled empirical identification of translated regions, but high-confidence detection of coding regions that overlap annotated coding regions has remained challenging. Here, we report a sensitive and robust algorithm that revealed the translation of 388 N-terminally truncated proteins in budding yeast-more than 30-fold more than previously known. We extensively experimentally validated them and defined two classes. The first class lacks large portions of the annotated protein and tends to be produced from a truncated transcript. We show that two such cases, Yap5truncation and Pus1truncation, have condition-specific regulation and distinct functions from their respective annotated isoforms. The second class of truncated protein isoforms lacks only a small region of the annotated protein and is less likely to be produced from an alternative transcript isoform. Many display different subcellular localizations than their annotated counterpart, representing a common strategy for dual localization of otherwise functionally identical proteins. A record of this paper's transparent peer review process is included in the supplemental information.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Isoformas de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Genoma , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição de Zíper de Leucina Básica
7.
Biomedicines ; 12(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672252

RESUMO

OBJECTIVE: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. METHODS: A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. RESULTS: Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. CONCLUSIONS: This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters.

8.
bioRxiv ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38559226

RESUMO

Long-read RNA sequencing has shed light on transcriptomic complexity, but questions remain about the functionality of downstream protein products. We introduce Biosurfer, a computational approach for comparing protein isoforms, while systematically tracking the transcriptional, splicing, and translational variations that underlie differences in the sequences of the protein products. Using Biosurfer, we analyzed the differences in 32,799 pairs of GENCODE annotated protein isoforms, finding a majority (70%) of variable N-termini are due to the alternative transcription start sites, while only 9% arise from 5' UTR alternative splicing. Biosurfer's detailed tracking of nucleotide-to-residue relationships helped reveal an uncommonly tracked source of single amino acid residue changes arising from the codon splits at junctions. For 17% of internal sequence changes, such split codon patterns lead to single residue differences, termed "ragged codons". Of variable C-termini, 72% involve splice- or intron retention-induced reading frameshifts. We found an unusual pattern of reading frame changes, in which the first frameshift is closely followed by a distinct second frameshift that restores the original frame, which we term a "snapback" frameshift. We analyzed long read RNA-seq-predicted proteome of a human cell line and found similar trends as compared to our GENCODE analysis, with the exception of a higher proportion of isoforms predicted to undergo nonsense-mediated decay. Biosurfer's comprehensive characterization of long-read RNA-seq datasets should accelerate insights of the functional role of protein isoforms, providing mechanistic explanation of the origins of the proteomic diversity driven by the alternative splicing. Biosurfer is available as a Python package at https://github.com/sheynkman-lab/biosurfer.

9.
BMC Genomics ; 25(1): 261, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38454321

RESUMO

Enterococcus faecalis, a formidable nosocomial and community-acquired opportunistic pathogen, can persist a wide range of extreme environments, including low pH and nutrient deficiency. Clarifying the survival mechanism of E. faecalis in low-pH conditions is the key to combating the infectious diseases caused by E. faecalis. In this study, we combined transcriptome profiling (RNA-seq) and transposon insertion sequencing (TIS) to comprehensively understand the genes that confer these features on E. faecalis. The metadata showed that genes whose products are involved in cation transportation and amino acid biosynthesis were predominantly differentially expressed under acid conditions. The products of genes such as opp1C and copY reduced the hydrion concentration in the cell, whereas those of gldA2, gnd2, ubiD, and ubiD2 mainly participated in amino metabolism, increasing matters to neutralize excess acid. These, together with the folE and hexB genes, which are involved in mismatch repair, form a network of E. faecalis genes necessary for its survival under acid conditions.


IMPORTANCE: As a serious nosocomial pathogen, Enterococcus faecalis was considered responsible for large numbers of infections. Its ability to survive under stress conditions, such as acid condition and nutrient deficiency was indispensable for its growth and infection. Therefore, understanding how E. faecalis survives acid stress is necessary for the prevention and treatment of related diseases. RNA-seq and TIS provide us a way to analyze the changes in gene expression under such conditions.


Assuntos
Enterococcus faecalis , Perfilação da Expressão Gênica , RNA-Seq , Enterococcus faecalis/genética , Genoma
10.
Exp Ther Med ; 27(4): 150, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476922

RESUMO

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer-associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence-associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy-induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well-studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence-like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

11.
Sensors (Basel) ; 24(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38544013

RESUMO

Earth observation by remote sensing plays a crucial role in granite extraction, and many current studies use thermal infrared data from sensors such as ASTER. The challenge lies in the low spatial resolution of these satellites, hindering precise rock type identification. A breakthrough emerges with the Thermal Infrared Spectrometer (TIS) on the Sustainable Development Science Satellite 1 (SDGSAT-1) launched by the Chinese Academy of Sciences. With an exceptional 30 m spatial resolution, SDGSAT-1 TIS opens avenues for accurate granite extraction using remote sensing. This study, exemplified in Xinjiang's Karamay region, introduces the BR-ISauvola method, leveraging SDGSAT-1 TIS data. The approach combines band ratio with adaptive k-value selection using local grayscale statistical features for Sauvola thresholding. Focused on large-scale granite extraction, results show F1 scores above 70% for Otsu, Sauvola, and BR-ISauvola. Notably, BR-ISauvola achieves the highest accuracy at 82.11%, surpassing Otsu and Sauvola by 9.62% and 0.34%, respectively. This underscores the potential of SDGSAT-1 TIS data as a valuable resource for granite extraction. The proposed method efficiently utilizes spectral information, presenting a novel approach for rapid granite extraction using remote sensing TIS imagery, even in scenarios with low spectral resolution and a single data source.

12.
ACS Appl Mater Interfaces ; 16(14): 17637-17648, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38549247

RESUMO

Aqueous zinc-ion batteries (ZIBs) are competitive among the elective candidates for electrochemical energy storage systems, but the intrinsic drawbacks of zinc metal anodes such as dendrites and corrosion severely hinder their large-scale application. Developing alternative anode materials capable of high reversibility and stability for storing Zn2+ ions is a feasible approach to circumvent the challenge. Herein, a sulfur-defect-induced TiS1.94 (D-TiS1.94) as a promising intercalation anode material for ZIBs is designed. The abundant Zn2+-storage active sites and lower Zn2+ migration barrier induced by sulfur defects endow D-TiS1.94 with a high capacity for Zn2+-storage (219.1 mA h g-1 at 0.05 A g-1) and outstanding rate capability (107.3 mA h g-1 at 5 A g-1). In addition, a slight volume change of 8.1% is identified upon Zn2+ storage, which favors a prolonged cycling life (50.3% capacity remaining in 1500 cycles). More significantly, the D-TiS1.94||ZnxMnO2 full battery demonstrates a high discharge capacity of 155.7 mA h g-1 with a capacity retention of 59.8% in 400 cycles. It has been estimated that the high-capacity, low-operation voltage, and long-life D-TiS1.94 can be a promising component of the ZIB anode material family, and the strategy proposed in this work will provide guidance to the defect engineering of high-performance electrode materials toward energy storage applications.

13.
Biomolecules ; 14(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38540708

RESUMO

Both the senescence of cancer cells and the maintenance of cancer stem cells seem to be mutually exclusive because senescence is considered a physiological mechanism that effectively suppresses tumor growth. Recent studies have revealed common signaling pathways between cellular senescence and the maintenance of stemness in cancer cells, thus challenging the conventional understanding of this process. Although the links between these processes have not yet been fully elucidated, emerging evidence indicates that senescent cancer cells can undergo reprograming to recover stemness. Herein, we provide a comprehensive overview of the close correlation between senescence and stemness reprograming in cancer cells, with a particular focus on the mechanisms by which senescent cancer cells recover their stemness in various tumor systems.


Assuntos
Neoplasias , Humanos , Transdução de Sinais , Células-Tronco Neoplásicas , Senescência Celular/fisiologia
14.
Plant Direct ; 8(2): e568, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38405354

RESUMO

Strigolactones (SLs), synthesized in plant roots, play a dual role in modulating plant growth and development, and in inducing the germination of parasitic plant seeds and arbuscular mycorrhizal fungi in the rhizosphere. As phytohormones, SLs are crucial in regulating branching and shaping plant architecture. Despite the significant impact of branching strategies on the yield performance of fruit crops, limited research has been conducted on SLs in these crops. In our study, we identified the transcript sequences of SL biosynthesis and signaling genes in olive (Olea europaea L.) using rapid amplification of cDNA ends. We predicted the corresponding protein sequences, analyzed their characteristics, and conducted molecular docking with bioinformatics tools. Furthermore, we quantified the expression levels of these genes in various tissues using quantitative real-time PCR. Our findings demonstrate the predominant expression of SL biosynthesis and signaling genes (OeD27, OeMAX3, OeMAX4, OeMAX1, OeD14, and OeMAX2) in roots and lateral buds, highlighting their importance in branching. Treatment with rac-GR24, an SL analog, enhanced the germination frequency of olive seeds in vitro compared with untreated embryos. Conversely, inhibition of SL biosynthesis with TIS108 increased lateral bud formation in a hard-to-root cultivar, underscoring the role of SLs as phytohormones in olives. These results suggest that modifying SL biosynthesis and signaling pathways could offer novel approaches for olive breeding, with potential applicability to other fruit crops.

15.
mSystems ; 9(2): e0100723, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38206015

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) is a large, oncogenic DNA virus belonging to the gammaherpesvirus subfamily. KSHV has been extensively studied with various high-throughput RNA-sequencing approaches to map the transcription start and end sites, the splice junctions, and the translation initiation sites. Despite these efforts, the comprehensive annotation of the viral transcriptome remains incomplete. In the present study, we generated a long-read sequencing data set of the lytic and latent KSHV transcriptome using native RNA and direct cDNA-sequencing methods. This was supplemented with Cap Analysis of Gene Expression sequencing based on a short-read platform. We also utilized data sets from previous publications for our analysis. As a result of this combined approach, we have identified a number of novel viral transcripts and RNA isoforms and have either corroborated or improved the annotation of previously identified viral RNA molecules, thereby notably enhancing our comprehension of the transcriptomic architecture of the KSHV genome. We also evaluated the coding capability of transcripts previously thought to be non-coding by integrating our data on the viral transcripts with translatomic information from other publications.IMPORTANCEDeciphering the viral transcriptome of Kaposi's sarcoma-associated herpesvirus is of great importance because we can gain insight into the molecular mechanism of viral replication and pathogenesis, which can help develop potential targets for antiviral interventions. Specifically, the identification of substantial transcriptional overlaps by this work suggests the existence of a genome-wide interference between transcriptional machineries. This finding indicates the presence of a novel regulatory layer, potentially controlling the expression of viral genes.


Assuntos
Herpesvirus Humano 8 , Herpesvirus Humano 8/genética , Transcriptoma/genética , Replicação Viral/genética , Perfilação da Expressão Gênica , RNA/metabolismo
16.
Support Care Cancer ; 32(1): 85, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38177894

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting adverse effect of anticancer therapy that complicates the lifestyle of many cancer survivors. There is currently no gold-standard for the assessment or management of CIPN. Subsequently, understanding the underlying mechanisms that lead to the development of CIPN is essential for finding better pharmacological therapy. Therapy-induced senescence (TIS) is a form of senescence that is triggered in malignant and non-malignant cells in response to the exposure to chemotherapy. Recent evidence has also suggested that TIS develops in the dorsal root ganglia of rodent models of CIPN. Interestingly, several components of the senescent phenotype are commensurate with the currently established primary processes implicated in the pathogenesis of CIPN including mitochondrial dysfunction, oxidative stress, and neuroinflammation. In this article, we review the literature that supports the hypothesis that TIS could serve as a holistic mechanism leading to CIPN, and we propose the potential for investigating senotherapeutics as means to mitigate CIPN in cancer survivors.


Assuntos
Antineoplásicos , Sobreviventes de Câncer , Doenças do Sistema Nervoso Periférico , Humanos , Antineoplásicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/patologia , Estresse Oxidativo
17.
Methods Mol Biol ; 2759: 25-41, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38285136

RESUMO

Companies dedicated to the large-scale propagation of plant species are known as biofactories or agricultural biotechnology companies. Globally, there are a large number of biofactories (large-scale production) or plant tissue culture laboratories (small-scale production) in charge of supplying commercial propagules of plants of economic interest. Each biofactory implements technological developments such as temporary immersion (TIS) systems that allow them to reduce costs. This chapter analyzes some of the biofactories established globally, the main plant species propagated, and whether or not they implement the use of TIS.


Assuntos
Agricultura , Imersão , Biotecnologia , Laboratórios , Reprodução
18.
Front Aging Neurosci ; 15: 1281581, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076538

RESUMO

Cellular senescence is a biological aging hallmark that plays a key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate the effectiveness of senotherapies for these diseases. However, the impact of senescence on brain aging and cognitive decline in the absence of neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic brain injury survivors, obese individuals, obstructive sleep apnea patients, and chronic kidney disease patients can suffer age-related brain changes like cognitive decline prematurely, suggesting that they may suffer accelerated senescence in the brain. Understanding the role of senescence in neurocognitive deficits linked to these conditions is crucial, especially considering the rapidly evolving field of senotherapeutics. Such treatments could help alleviate early brain aging in these patients, significantly reducing patient morbidity and healthcare costs. This review provides a translational perspective on how cellular senescence plays a role in brain aging and age-related cognitive decline. We also discuss important caveats surrounding mainstream senotherapies like senolytics and senomorphics, and present emerging evidence of hyperbaric oxygen therapy and immune-directed therapies as viable modalities for reducing senescent cell burden.

19.
Mol Cell ; 83(24): 4509-4523.e11, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38134885

RESUMO

The cytoplasm is highly compartmentalized, but the extent and consequences of subcytoplasmic mRNA localization in non-polarized cells are largely unknown. We determined mRNA enrichment in TIS granules (TGs) and the rough endoplasmic reticulum (ER) through particle sorting and isolated cytosolic mRNAs by digitonin extraction. When focusing on genes that encode non-membrane proteins, we observed that 52% have transcripts enriched in specific compartments. Compartment enrichment correlates with a combinatorial code based on mRNA length, exon length, and 3' UTR-bound RNA-binding proteins. Compartment-biased mRNAs differ in the functional classes of their encoded proteins: TG-enriched mRNAs encode low-abundance proteins with strong enrichment of transcription factors, whereas ER-enriched mRNAs encode large and highly expressed proteins. Compartment localization is an important determinant of mRNA and protein abundance, which is supported by reporter experiments showing that redirecting cytosolic mRNAs to the ER increases their protein expression. In summary, the cytoplasm is functionally compartmentalized by local translation environments.


Assuntos
Retículo Endoplasmático , Proteínas , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Proteínas/metabolismo , Citosol/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transporte Proteico , Biossíntese de Proteínas
20.
Adv Rehabil Sci Pract ; 12: 27536351231211718, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029060

RESUMO

Background: Trunk function is a prerequisite for functional activity; thus, it is crucial to carry out proper assessments and interventions. However, there is no clear indicator for trunk function evaluation in patients with stroke. To understand the effects of interventions over time, it is important to adopt responsive clinical indicators. Purpose: To examine the Trunk Impairment Scale (TIS) (Fujiwara version) in terms of responsiveness and the minimal clinically important difference (MCID). Methods: In total, 55 patients who experienced an acute stroke were evaluated on the seventh day of hospitalization and the day before discharge. The responsiveness of the TIS was assessed by the effect size and standardized response mean (SRM). Additionally, an MCID study was conducted to examine the amount of change in TIS scores required to indicate a clinically meaningful change, which was determined by the presence or absence of improvement in the activities of daily living. Results: The SRM of the TIS was 1.42. Additionally, the MCID was determined to be 3 points. Conclusion: The TIS score improved over time and a 3-point improvement in the TIS score was associated with improvement in the activities of daily living. Thus, this scale's clinical sensitivity and MCID have been established in patients with stroke.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA