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1.
Biomed Pharmacother ; 175: 116620, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653113

RESUMO

There is a growing interest in the role of the miRNA family in human cancer. The miRNA-192 family is a group of conserved small RNAs, including miR-192, miR-194, and miR-215. Recent studies have shown that the incidence and mortality of breast cancer have been increasing epidemiologically year by year, and it is urgent to clarify the pathogenesis of breast cancer and seek new diagnostic and therapeutic methods. There is increasing evidence that miR-192 family members may be involved in the occurrence and development of breast cancer. This review describes the regulatory mechanism of the miRNA-192 family affecting the malignant behavior of breast cancer cells and evaluates the value of the miRNA-192 family as a diagnostic and prognostic biomarker for breast cancer. It is expected that summarizing and discussing the relationship between miRNA-192 family members and breast cancer, it will provide a new direction for the clinical diagnosis and treatment of breast cancer and basic medical research.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Biomarcadores Tumorais/genética , Animais , Prognóstico
2.
Sensors (Basel) ; 24(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38610242

RESUMO

Current real-time direction judgment systems are inaccurate and insensitive, as well as limited by the sampling rate of analog-to-digital converters. To address this problem, we propose a dynamic real-time direction judgment system based on an integral dual-frequency laser interferometer and field-programmable gate array technology. The optoelectronic signals resulting from the introduction of a phase subdivision method based on the amplitude resolution of the laser interferometer when measuring displacement are analyzed. The proposed system integrates the optoelectronic signals to increase the accuracy of its direction judgments and ensures these direction judgments are made in real time by dynamically controlling the integration time. Several experiments were conducted to verify the performance of the proposed system. The results show that, compared with current real-time direction judgment systems, the proposed system makes accurate judgements during low-speed motions and can update directions within 0.125 cycles of the phase difference change at different speeds. Moreover, a sweep frequency experiment confirmed the system's ability to effectively judge dynamic directions. The proposed system is capable of accurate and real-time directional judgment during low-speed movements of a table in motion.

3.
Int J Nanomedicine ; 19: 1985-2004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435754

RESUMO

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.


Assuntos
Neoplasias , Pontos Quânticos , Animais , Camundongos , Cobre/farmacologia , Apoptose , Carbono/farmacologia
4.
Front Immunol ; 15: 1368203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545108

RESUMO

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.


Assuntos
Células Espumosas , Traumatismos da Medula Espinal , Humanos , Células Espumosas/patologia , Traumatismos da Medula Espinal/metabolismo , Macrófagos/metabolismo , Sistema Nervoso Central/metabolismo
5.
Ecotoxicol Environ Saf ; 269: 115815, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091675

RESUMO

Flame retardants (FRs) have raised public concerns because of their environmental persistence and negative impacts on human health. Recent evidence has revealed that many FRs exhibit reproductive toxicities and transgenerational impacts, whereas the toxic effects of FRs on germ cells remain barely explored. Here we investigated the multigenerational effects of three flame retardants (TBBPA, TCEP and TCPP) on germ cell development in Caenorhabditis elegans, and examined the germ cell mutagenicity of these FRs by using whole genome sequencing. Parental exposure to three FRs markedly increased germ cell apoptosis, and impeded oogenesis in F1-F6 offspring. In addition, the double-increased mutation frequencies observed in progeny genomes uncover the mutagenic actions of FRs on germ cells. Analysis of mutation spectra revealed that these FRs predominantly induced point mutations at A:T base pairs, whereas both small and large indels were almost unaffected. These results revealed the long-term effects of FRs on development and genomic stability of germ cells, which may pose risks to environmental organisms and human reproductive health. Taken together, our findings suggest that germ cell mutagenicity should be carefully examined for the environmental risk assessment of FRs and other emerging pollutants.


Assuntos
Poluentes Ambientais , Retardadores de Chama , Animais , Humanos , Retardadores de Chama/toxicidade , Retardadores de Chama/análise , Caenorhabditis elegans/genética , Mutagênicos , Poluentes Ambientais/toxicidade , Medição de Risco , Éteres Difenil Halogenados/análise
7.
Nutrients ; 15(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37960231

RESUMO

Skeletal muscle atrophy is a frequent complication after spinal cord injury (SCI) and can influence the recovery of motor function and metabolism in affected patients. Delaying skeletal muscle atrophy can promote functional recovery in SCI rats. In the present study, we investigated whether a combination of body weight support treadmill training (BWSTT) and glycine and N-acetylcysteine (GlyNAC) could exert neuroprotective effects, promote motor function recovery, and delay skeletal muscle atrophy in rats with SCI, and we assessed the therapeutic effects of the double intervention from both a structural and functional viewpoint. We found that, after SCI, rats given GlyNAC alone showed an improvement in Basso-Beattie-Bresnahan (BBB) scores, gait symmetry, and results in the open field test, indicative of improved motor function, while GlyNAC combined with BWSTT was more effective than either treatment alone at ameliorating voluntary motor function in injured rats. Meanwhile, the results of the skeletal muscle myofiber cross-sectional area (CSA), hindlimb grip strength, and acetylcholinesterase (AChE) immunostaining analysis demonstrated that GlyNAC improved the structure and function of the skeletal muscle in rats with SCI and delayed the atrophication of skeletal muscle.


Assuntos
Acetilcisteína , Traumatismos da Medula Espinal , Humanos , Ratos , Animais , Acetilcisteína/metabolismo , Ratos Sprague-Dawley , Acetilcolinesterase/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Peso Corporal , Recuperação de Função Fisiológica/fisiologia
8.
Front Microbiol ; 14: 1265435, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965558

RESUMO

White birch (Betula platyphylla Suk.) is a typical pioneer tree species that is important in forest restoration in northern China, Japan, and Korea. In the present study, 37 isolates were obtained from B. platyphylla rhizosphere soils in Heilongjiang Province; they were identified as T. pleuroticola (3 isolates), T. virens (2 isolates), T. hamatum (8 isolates), T. atroviride (21 isolates, dominant species) and T. asperelloides (3 isolates). Stress tolerance tests (salt, alkali, and nutritional stress that simulated saline alkali or barren soil) and confrontation assays (with four pathogens) were performed to determine which isolates had good biocontrol ability in barren soil; the results show that T. atroviride was outstanding. Then, in order to determine the effect of T. atroviride on plants and soil, Gynura cusimbua seeds were sown and treated with a T. atroviride spore suspension, as was unsown soil. The seedlings treated using T. atroviride had significantly greater height, stem diameter, soluble protein content, soluble sugar content, and malonaldehyde (MDA) content and their catalase (CAT) activity was also significantly increased. In addition, when the plants were inoculated with Alternaria alternata, the plants treated using T. atroviride had stronger CAT activity, significantly higher soluble protein content and soluble sugar content, and significantly lower MDA content, which indicates stronger resistance and less injury caused by the pathogen. In addition, T. atroviride not only increased the content of available nitrogen and available phosphorus in the soil, but also promoted G. cusimbua seedlings' absorption of available nitrogen and available phosphorus. Thus, the characteristics of T. atroviride may make it the main factor that helps B. platyphylla colonise cut-over lands. T. atroviride, a promising biocontrol candidate, can be used in agriculture and forestry.

9.
Inflammation ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37975960

RESUMO

Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI.

10.
BMC Med ; 21(1): 461, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996906

RESUMO

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.


Assuntos
Técnicas de Ablação , Fibrilação Atrial , Ablação por Cateter , Embolia Intracraniana , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Estudos Prospectivos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/prevenção & controle , Incidência , Técnicas de Ablação/efeitos adversos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Recidiva
11.
Heliyon ; 9(11): e21448, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37954370

RESUMO

Data privacy in smart homes is receiving increasing attention due to the growing adoption of smart appliances. Adoption of smart appliances can bring benefits, including energy consumption reduction. This study investigates how people made the trade-offs between sharing privacy-sensitive data and the potential environmental and economic benefits of smart home energy appliances using discrete choice modeling. The findings reveal that the trade-off is mainly affected by four product attributes: the type of data that is processed, the reason why this data is processed, the data sharing frequency, and the financial benefit gained from the smart home appliances. Specifically, individuals tend to share less data daily for their daily routine convenience and demand a (theoretical) financial compensation for the data sharing. The results also show that privacy attitudes are not related to data sharing preferences, while socio-demographics, including gender, age, and income, are. The results emphasize the gap between people's attitudes and behaviors regarding data privacy. This research serves as a foundation for further investigations and can be used by smart appliance retailers, manufacturers, and governments for designing research and development focus and energy reduction incentives, respectively.

12.
Int J Ophthalmol ; 16(9): 1406-1416, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37724269

RESUMO

With the rapid development of computer technology, the application of artificial intelligence (AI) to ophthalmology has gained prominence in modern medicine. As modern optometry is closely related to ophthalmology, AI research on optometry has also increased. This review summarizes current AI research and technologies used for diagnosis in optometry, related to myopia, strabismus, amblyopia, optical glasses, contact lenses, and other aspects. The aim is to identify mature AI models that are suitable for research on optometry and potential algorithms that may be used in future clinical practice.

13.
J Environ Manage ; 346: 119024, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37738728

RESUMO

Radiocarbon (14C), stable carbon isotope (13C), and levoglucosan in PM2.5 were measured in two northern Chinese cities during haze events and nonhaze periods in January 2019, to ascertain the sources and their differences in carbonaceous aerosols between the two periods. The contribution of primary vehicle emissions (17.8 ± 3.7%) to total carbon in Beijing during that haze event was higher than that of primary coal combustion (7.3 ± 4.2%), and it increased significantly (7.1%) compared to the nonhaze period. The contribution of primary vehicle emissions (4.1 ± 2.8%) was close to that of primary coal combustion (4.3 ± 3.3%) during the haze event in Xi'an, and the contribution of primary vehicle emissions decreased by 5.8% compared to the nonhaze period. Primary biomass burning contributed 21.1 ± 10.5% during the haze event in Beijing and 40.9 ± 6.6% in Xi'an (with an increase of 3.3% compared with the nonhaze period). The contribution of secondary fossil fuel sources to total secondary organic carbon increased by 29.2% during the haze event in Beijing and by 18.4% in Xi'an compared to the nonhaze period. These results indicate that specific management measures for air pollution need to be strengthened in different Chinese cities in the future, that is, controlling vehicle emissions in Beijing and restricting the use of coal and biomass fuels in winter in Xi'an.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Cidades , Material Particulado/análise , Monitoramento Ambiental/métodos , Carvão Mineral/análise , Estações do Ano , Carbono/análise , Aerossóis/análise , China
14.
Opt Lett ; 48(15): 4149-4152, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37527140

RESUMO

Ring skeleton vibrations of aromatic series are dominant in Raman spectroscopy compared with the C-H stretching vibrations. When a laser-induced plasma (LIP) was generated in a mixed solution of naphthalene and benzene, an anomalous enhancement was observed in stimulated Raman scattering (SRS) of aromatic C-H stretching vibrations of naphthalene (3055 cm-1). However, SRS of C-H stretching vibrations of benzene at 3060 cm-1 disappeared. The LIP produced electrons and cations, and the transient production of ionized material contributed to the enhancement of SRS of C-H vibrations of naphthalene. Density functional theory calculations showed that the C-H Raman activity of the naphthalene molecules in (naphthalene-benzene)+ heterodimer was significantly enhanced compared with neutral naphthalene. In addition, SRS pulse durations were better compressed in pure benzene and naphthalene due to the self-focusing effect.

15.
Int J Biol Macromol ; 252: 126361, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37591430

RESUMO

Diatom containing different active biological macromolecules are thought to be an excellent microbial cell factory. Phaeodactylum tricornutum, a model diatom, is a superb chassis organism accumulating chrysolaminarin with important bioactivities. However, the characteristic of chrysolaminarin accumulation and molecular mechanism of the fluctuated chrysolaminarin in diatom are still unknown. In this study, physiological data and transcriptomic analysis were carried out to clarify the mechanism involved in chrysolaminarin fluctuation. The results showed that chrysolaminarin content fluctuated, from 7.41 % dry weight (DW) to 40.01 % DW during one light/dark cycle, increase by day and decrease by night. The similar fluctuated characteristic was also observed in neutral lipid content. Genes related to the biosynthesis of chrysolaminarin and neutral lipid were up-regulated at the beginning of light-phase, explaining the accumulation of these biological macromolecules. Furthermore, genes involved in carbohydrate degradation, cell cycle, DNA replication and mitochondria-localized ß-oxidation were up-regulated at the end of light phase and at the beginning of dark phase hinting an energy transition of carbohydrate to cell division during the dark period. Totally, our findings provide important information for the regulatory mechanism in the diurnal fluctuation of chrysolaminarin. It would also be of great help for the mass production of economical chrysolaminarin in marine diatom.


Assuntos
Diatomáceas , Transcriptoma , Diatomáceas/genética , Perfilação da Expressão Gênica , Lipídeos , Carboidratos
16.
Food Chem Toxicol ; 178: 113902, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37331561

RESUMO

The platinum compound oxaliplatin is a widely used chemotherapeutic drug that shows a broad spectrum of activity in various human tumors. While the treatment-related side effects of oxaliplatin on directly treated individuals have been well-documented, little is known about the influence of oxaliplatin on germ cells and non-exposed progenies. Here we investigated the reproductive toxicity of oxaliplatin in a 3R-compliant in vivo model Caenorhabditis elegans, and evaluated the germ cell mutagenicity of oxaliplatin by using whole genome sequencing. Our results indicated that oxaliplatin treatment significantly disrupts development of spermatids and oocytes. By treating parental worms with oxaliplatin for three successive generations, sequencing data unveiled the mutagenic effects of oxaliplatin on germ cells. Analysis of genome-wide mutation spectra showed the preferentially induction of indels by oxaliplatin. In addition, we uncovered the involvement of translesion synthesis polymerase ζ in modulating mutagenic effects of oxaliplatin. These findings suggest that germ cell mutagenicity is worthy of consideration for the health risk assessment of chemotherapeutic drugs, while the combined use of alternative in vivo models and next generation sequencing technology appears to be a promising way for the preliminary safety assessment of various drugs.


Assuntos
Caenorhabditis elegans , Mutagênicos , Masculino , Animais , Humanos , Oxaliplatina/toxicidade , Mutagênicos/toxicidade , Caenorhabditis elegans/genética , Mutagênese , Células Germinativas
17.
Arch Toxicol ; 97(8): 2261-2272, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37209179

RESUMO

In contrast to somatic mutations, mutations in germ cells affect every cell of any organism derived from the germ cell and therefore are related to numerous genetic diseases. However, there is no suitable assay to evaluate the mutagenic sensitivities of both male and female germ cells. The main type of Caenorhabditis elegans (C. elegans) is hermaphroditic, where spermatogenesis and oogenesis occur chronologically at specific stages, allowing induction of mutations in either sperm or eggs exclusively. In this study, we used the alkylating agent ethyl methanesulfonate and N-ethyl-N-nitrosourea to induce germline mutations in C. elegans at different developmental stages and analyzed mutation frequency and mutational spectrum from data gathered using next-generation sequencing (NGS) technology. Our results revealed low spontaneous mutation rates of C. elegans, along with distinct mutagenic effects elicited by the two mutagens. Our data show that the parental worms treated during germ cell mitosis, spermatogenesis, and oogenesis resulted in different mutation frequencies in their offspring, and female germ cells could be very susceptible to mutagen exposure during oogenesis. In summary, our study indicates that the use of C. elegans and its specific chronological hermaphroditism would be a promising way to explore the sensitivities of both male and female germ cells to mutagens.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Masculino , Feminino , Caenorhabditis elegans/genética , Mutagênicos/toxicidade , Sêmen , Células Germinativas/metabolismo , Espermatogênese/genética , Sequenciamento Completo do Genoma , Proteínas de Caenorhabditis elegans/genética
18.
Acta Pharmacol Sin ; 44(8): 1549-1563, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37055533

RESUMO

Receptor-interacting protein kinase 1 (RIPK1) contributes to necroptosis. Our previous study showed that pharmacological or genetic inhibition of RIPK1 protects against ischemic stroke-induced astrocyte injury. In this study, we investigated the molecular mechanisms underlying RIPK1-mediated astrocyte injury in vitro and in vivo. Primary cultured astrocytes were transfected with lentiviruses and then subjected to oxygen and glucose deprivation (OGD). In a rat model of permanent middle cerebral artery occlusion (pMCAO), lentiviruses carrying shRNA targeting RIPK1 or shRNA targeting heat shock protein 70.1B (Hsp70.1B) were injected into the lateral ventricles 5 days before pMCAO was established. We showed that RIPK1 knockdown protected against OGD-induced astrocyte damage, blocked the OGD-mediated increase in lysosomal membrane permeability in astrocytes, and inhibited the pMCAO-induced increase in astrocyte lysosome numbers in the ischemic cerebral cortex; these results suggested that RIPK1 contributed to the lysosomal injury in ischemic astrocytes. We revealed that RIPK1 knockdown upregulated the protein levels of Hsp70.1B and increased the colocalization of Lamp1 and Hsp70.1B in ischemic astrocytes. Hsp70.1B knockdown exacerbated pMCAO-induced brain injury, decreased lysosomal membrane integrity and blocked the protective effects of the RIPK1-specific inhibitor necrostatin-1 on lysosomal membranes. On the other hand, RIPK1 knockdown further exacerbated the pMCAO- or OGD-induced decreases in the levels of Hsp90 and the binding of Hsp90 to heat shock transcription factor-1 (Hsf1) in the cytoplasm, and RIPK1 knockdown promoted the nuclear translocation of Hsf1 in ischemic astrocytes, resulting in increased Hsp70.1B mRNA expression. These results suggest that inhibition of RIPK1 protects ischemic astrocytes by stabilizing lysosomal membranes via the upregulation of lysosomal Hsp70.1B; the mechanism underlying these effects involves decreased Hsp90 protein levels, increased Hsf1 nuclear translocation and increased Hsp70.1B mRNA expression.


Assuntos
Astrócitos , Isquemia Encefálica , Ratos , Animais , Ratos Sprague-Dawley , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/farmacologia , Infarto da Artéria Cerebral Média/metabolismo , Lisossomos/metabolismo , RNA Interferente Pequeno/farmacologia , RNA Mensageiro/metabolismo , Glucose/metabolismo , Isquemia Encefálica/metabolismo
19.
Front Nutr ; 10: 1099143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937344

RESUMO

Spinal cord injury leads to loss of innervation of skeletal muscle, decreased motor function, and significantly reduced load on skeletal muscle, resulting in atrophy. Factors such as braking, hormone level fluctuation, inflammation, and oxidative stress damage accelerate skeletal muscle atrophy. The atrophy process can result in skeletal muscle cell apoptosis, protein degradation, fat deposition, and other pathophysiological changes. Skeletal muscle atrophy not only hinders the recovery of motor function but is also closely related to many systemic dysfunctions, affecting the prognosis of patients with spinal cord injury. Extensive research on the mechanism of skeletal muscle atrophy and intervention at the molecular level has shown that inflammation and oxidative stress injury are the main mechanisms of skeletal muscle atrophy after spinal cord injury and that multiple pathways are involved. These may become targets of future clinical intervention. However, most of the experimental studies are still at the basic research stage and still have some limitations in clinical application, and most of the clinical treatments are focused on rehabilitation training, so how to develop more efficient interventions in clinical treatment still needs to be further explored. Therefore, this review focuses mainly on the mechanisms of skeletal muscle atrophy after spinal cord injury and summarizes the cytokines and signaling pathways associated with skeletal muscle atrophy in recent studies, hoping to provide new therapeutic ideas for future clinical work.

20.
Curr Issues Mol Biol ; 45(2): 1570-1586, 2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36826046

RESUMO

ATP-binding cassette (ABC) transporters are involved in transporting multiple substrates, such as toxins, and may be important for the survival of Trichoderma when encountering biotic toxins. In this study, genome searching revealed that there are 44 ABC transporters encoded in the genome of Trichoderma asperellum. These ABC transporters were divided into six types based on three-dimensional (3D) structure prediction, of which four, represented by 39 ABCs, are involved in transport and the remaining two, represented by 5 ABCs, are involved in regulating translation. The characteristics of nucleotide-binding domain (NBD) are important in the identification of ABC proteins. Even though the 3D structures of the 79 NBDs in the 44 ABCs are similar, multiple sequence alignment showed they can be divided into three classes. In total, 794 motifs were found in the promoter regions of the 44 ABC genes, of which 541 were cis-regulators related to stress responses. To characterize how their ABCs respond when T. asperellum interact with fungi or plants, T. asperellum was cultivated in either minimal media (MM) control, C-hungry, N-hungry, or poplar medium (PdPap) to simulate normal conditions, competition with pathogens, interaction with pathogens, and interaction with plants, respectively. The results show that 17 of 39 transport ABCs are highly expressed in at least one condition, whereas four of the five translation-regulating ABCs are highly expressed in at least one condition. Of these 21 highly expressed ABCs, 6 were chosen for RT-qPCR expression under the toxin stress of phytopathogen Alternaria alternata, and the results show ABC01, ABC04, ABC05, and ABC31 were highly expressed and may be involved in pathogen interaction and detoxifying toxins from A. alternata.

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