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1.
Reproduction ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38744310

RESUMO

Previous studies from our group and others have shown increased IncRNA H19 expression in both the eutopic endometrium and the ectopic endometriosis tissue during endometriosis. In this study, we use immunofluorescence, immunohistochemistry and protein quantification to determine that levels of aerobic glycolysis and histone lactylation; which we show are increased in endometriosis tissues. In HESC cells (Human Endometrial Stromal Cells), we found that high H19 expression resulted in abnormal glucose metabolism by examining the levels of glucose, lactate, and ATP and measuring protein levels of enzymes that participate in glycolysis. At the same time, immunofluorescence and western blotting demonstrated increased histone lactylation in H19 overexpressing cells. Altering aerobic glycolysis and histone lactylation levels through the addition of Nala (sodium lactate) and 2-DG demonstrated that increased aerobic glycolysis and histone lactylation levels resulted in enhanced cell proliferation and cell migration, contributing to endometriosis. To validate these findings in vivo, we constructed an endometriosis mouse model, demonstrating similar changes in endometriosis tissues in vivo. Both aerobic glycolysis and histone lactylation levels were elevated in endometriotic lesions. Taken together, these data demonstrate elevated expression levels of H19 in endometriosis patients promote abnormal glucose metabolism and elevated histone lactylation levels in vivo, enhancing cell proliferation and migration and promoting the progression of endometriosis. Our study provides a functional link between H19 expression and histone lactylation and glucose metabolism in endometriosis, providing new insights into disease mechanisms that could result in novel therapeutic approaches.

2.
J Psychiatr Res ; 175: 333-342, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38761515

RESUMO

The current diagnostic criteria for depression do not sufficiently reflect its heterogeneous clinical presentations. Associations between adverse childhood experiences (ACEs), allostatic load (AL), and depression subtypes have not been extensively studied. Depression subtypes were determined based on clinical presentations, and their relationships to AL biomarkers and ACEs were elucidated in a sample of middle-aged and older adults. Participants from the Canadian Longitudinal Study on Aging who screened positive for depression were included (n = 3966). Depression subtypes, AL profiles and ACE profiles were determined with latent profile analyses, and associations between them were determined using multinomial logistic regression. Four depression subtypes were identified: positive affect, melancholic, typical, and atypical. Distinct associations between depression subtypes, stressor profiles and covariates were observed. Among the subtypes compared to positive affect, atypical subtype had the most numerous significant associations, and the subtypes had unique relationships to stressor profiles. Age, sex, smoking status, chronic conditions, marital status, and physical activity were significant covariates. The present study describes distinct associations between depression subtypes and measures of stress (objective and self-reported), as well as related factors that differentiate subtypes. The findings may inform more targeted and integrated clinical management strategies for depression in individuals exposed to multiple stressors.

3.
iScience ; 27(5): 109713, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38746668

RESUMO

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

4.
Plant Commun ; : 100856, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431772

RESUMO

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

5.
Sci Total Environ ; 925: 171818, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508245

RESUMO

Hexavalent chromium [Cr(VI)] is an environmental pollutant known for its strong oxidizing and carcinogenic effects. However, its potential to induce ferroptosis in poultry remains poorly understood. This study aims to investigate the induction of ferroptosis by Cr(VI) in DF-1 cells and elucidate the underlying mechanisms. DF-1 cells exposed to Cr(VI) showed increased lipid reactive oxygen species and changes in ferroptosis marker genes (decreased expression of GPX4 and increased expression of COX2). Notably, the addition of the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) can reverse this effect. During the cell death process, Cr(VI) induced ferritinophagy, disrupting iron homeostasis and releasing labile iron ions. We predicted by docking that these iron ions would bind to mitochondrial membrane proteins through virtual docking. This binding was validated through colocalization analysis. In addition, Cr(VI) caused mitophagy, which releases additional ferrous ions. Therefore, Cr(VI) can induce the simultaneous release of ferrous ions through these pathways, thereby exacerbating lipid peroxidation and ultimately triggering ferroptosis in DF-1 cells. This study demonstrates that Cr(VI) can induce ferroptosis in DF-1 cells by disrupting intracellular iron homeostasis and providing valuable insights into the toxic effects of Cr(VI) in poultry and potentially other organisms.


Assuntos
Cromo , Ferroptose , Mitofagia , Ferro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Homeostase , Íons
6.
Nat Commun ; 15(1): 2462, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503749

RESUMO

Medium-sized-ring compounds have been recognized as challenging synthetic targets in organic chemistry. Especially, the difficulty of synthesis will be augmented if an E-olefin moiety is embedded. Recently, photo-induced dearomative cycloaddition reactions that proceed via energy transfer mechanism have witnessed significant developments and provided powerful methods for the organic transformations that are not easily realized under thermal conditions. Herein, we report an intramolecular dearomative [5 + 4] cycloaddition of naphthalene-derived vinylcyclopropanes under visible-light irradiation and a proper triplet photosensitizer. The reaction affords dearomatized polycyclic molecules possessing a nine-membered-ring with an E-olefin moiety in good yields (up to 86%) and stereoselectivity (up to 8.8/1 E/Z). Detailed computational studies reveal the origin behind the favorable formation of the thermodynamically less stable isomers. Diverse derivations of the dearomatized products have also been demonstrated.

7.
J Transl Med ; 22(1): 196, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395901

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose global prevalence is rapidly increasing. Acetyl CoA carboxylases 1 (ACACA) is the key enzyme that controls the rate of fatty acid synthesis. Hence, it is crucial to investigate the function of ACACA in regulating lipid metabolism during the progress of NAFLD. METHODS: Firstly, a fatty liver mouse model was established by high-fat diet at 2nd, 12th, and 20th week, respectively. Then, transcriptome analysis was performed on liver samples to investigate the underlying mechanisms and identify the target gene of the occurrence and development of NAFLD. Afterwards, lipid accumulation cell model was induced by palmitic acid and oleic acid (PA ∶ OA molar ratio = 1∶2). Next, we silenced the target gene ACACA using small interfering RNAs (siRNAs) or the CMS-121 inhibitor. Subsequently, experiments were performed comprehensively the effects of inhibiting ACACA on mitochondrial function and lipid metabolism, as well as on AMPK- PPARα- CPT1A pathway. RESULTS: This data indicated that the pathways significantly affected by high-fat diet include lipid metabolism and mitochondrial function. Then, we focus on the target gene ACACA. In addition, the in vitro results suggested that inhibiting of ACACA in vitro reduces intracellular lipid accumulation, specifically the content of TG and TC. Furthermore, ACACA ameliorated mitochondrial dysfunction and alleviate oxidative stress, including MMP complete, ATP and ROS production, as well as the expression of mitochondria respiratory chain complex (MRC) and AMPK proteins. Meanwhile, ACACA inhibition enhances lipid metabolism through activation of PPARα/CPT1A, leading to a decrease in intracellular lipid accumulation. CONCLUSION: Targeting ACACA can reduce lipid accumulation by mediating the AMPK- PPARα- CPT1A pathway, which regulates lipid metabolism and alleviates mitochondrial dysfunction.


Assuntos
Acetil-CoA Carboxilase , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , PPAR alfa/metabolismo , Acetil-CoA Carboxilase/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo
8.
J Am Chem Soc ; 146(7): 4333-4339, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38324359

RESUMO

Ru/Cu dual catalysis has been applied for Z-retentive asymmetric allylic substitution reactions of aldimine esters. This reaction provides an enantioselective synthesis of chiral Z-olefins in high yields (up to 91% yield) with excellent enantioselectivity (up to 98% ee) under mild conditions. The previously unreacted trisubstituted allylic electrophiles under Ir catalytic system are found to be compatible, affording the stereoretentive products in either Z- or E-form. Both linear and branched allylic electrophiles are suitable substrates with excellent reaction outcomes. Notably, Ru and Cu complexes are added in one-pot and simplifies the manipulation of this protocol and self-sorting phenomena could be observed in this Ru/Cu dual catalytic system.

9.
Org Lett ; 26(7): 1501-1505, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38349077

RESUMO

Asymmetric C-H trifluoromethylalkylation represents a novel and straightforward synthetic method for the construction of chiral CF3-containing compounds. However, the reported examples remain limited, given the challenges of reactivity and enantioselective control. Herein, we report a SCpRh(III)-catalyzed asymmetric aryl and alkenyl C-H trifluoromethylalkylation reaction with ß-trifluoromethyl-α,ß-unsaturated ketones. The chiral CF3-bearing adducts were obtained in moderate to good yields with high enantioselectivity (up to 81% yield and 96% ee). The reaction features mild conditions and broad substrate scope. The chiral CF3-bearing products could undergo diverse functional group transformations.

10.
J Affect Disord ; 351: 888-894, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38320661

RESUMO

BACKGROUND: This study aimed to investigate the symptom patterns of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in a matched nationally representative sample of the Canadian population. We also tested whether childhood maltreatment (CM) exposures and sex would be linked with different symptom patterns. METHODS: A total of 3296 participants from the Canadian Community Health Survey-Mental Health with complete information on MDD and GAD symptoms and being matched on the studied sociodemographic characteristics were included in the current study. Network analysis was performed to examine the MDD-GAD symptom network, network stability and centrality indices were also estimated. Finally, network comparison in connectivity patterns was conducted to explore the impact of maltreatment experience and sex differences in the MDD-GAD symptom networks. RESULTS: The CM group had stronger network connections and showed differences in the network structures from the non-CM group. In the CM group, depressed mood and diminished interest were central symptoms and strongly connected with other symptoms. Additionally, females had stronger connections in the MDD-GAD symptom network than males, and sleep disturbance was a central symptom for females, alongside depressed mood and diminished interest. LIMITATIONS: The cross-sectional design restricts our capacity to establish longitudinal or causal connections between symptoms. CONCLUSIONS: Depressed mood was the most central node that was strongly connected with other symptoms in the network. Distinct MDD-GAD symptom networks were discovered in the CM and the female group when compared to their counterparts. Noteworthy, individuals with CM had a stronger correlation between worry and suicidal ideation. Clinical management and intervention efforts should pay close attention to these core symptoms to yield optimal treatment effects, particularly for females and individuals with CM.


Assuntos
Transtorno Depressivo Maior , Humanos , Masculino , Feminino , Transtorno Depressivo Maior/psicologia , Comorbidade , Estudos Transversais , Canadá/epidemiologia , Ansiedade
11.
Chem Soc Rev ; 53(4): 2056-2098, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38214051

RESUMO

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

12.
Acta Pharmacol Sin ; 45(5): 1077-1092, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38267547

RESUMO

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.


Assuntos
Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Sepse , Animais , Sepse/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Ratos , Administração Intravenosa
13.
Chemosphere ; 349: 140910, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072197

RESUMO

Both nanoplastics (NPs) and imidacloprid (IMI) are widely distributed in the environment and have attracted significant attention due to their adverse effects on ecosystems. Constructed wetlands have the potential to remove IMI, but there is still limited understanding of how wetland plants interact with IMI, especially when influenced by different charged NPs. This study assessed their ecotoxicological effects, as well as the fate and transformation of IMI in papyrus (Cyperus papyrus L.) under the influence of different charged NPs and identified key driving genes in the plant. Results show that simultaneous exposure to positively charged PS-NH2 and IMI inhibited plant growth. The combined action of NPs and IMI intensified their toxicity, enhancing lipid peroxidation and altering antioxidant enzyme activities. The IMI removal efficiency, which was primarily driven by biodegradation, was 80.61%, 88.91%, and 74.71% in the IMI-alone, co-IMI/PS_COOH, and co-IMI/PS_NH2 systems, respectively. PS-NH2 restricted the roots-to-shoots translocation ability of IMI. PS-COOH enhanced IMI oxidation and nitro reduction, while PS-NH2 inhibited 2-OH-IMI dehydrogenation to IMI-olefin in papyrus. Transcriptomics and gene network analysis identified the genes encoding CYP450 enzymes, reductases, hydrolases, dehydrogenases, and peroxidases as those influencing IMI biodegradation. These enzymes play a crucial role in the hydroxylation, dehydrogenation, reduction, and oxidation processes during biodegradation of IMI in the presence of NPs. This study expands the understanding of the impact of differently charged NPs on the IMI remediation efficacy of papyrus, thus providing new insights into the phytoremediation of organic contaminants in constructed wetlands.


Assuntos
Cyperus , Ecossistema , Cyperus/metabolismo , Microplásticos/metabolismo , Biodegradação Ambiental , Plantas
14.
Sci Total Environ ; 912: 168924, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38036146

RESUMO

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.


Assuntos
Atrazina , Melatonina , Nucleotídeos Cíclicos , Animais , Camundongos , Atrazina/toxicidade , Atrazina/metabolismo , Melatonina/metabolismo , Piroptose , Interferons/metabolismo , Interferons/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos Endogâmicos C57BL , Mitocôndrias , DNA Mitocondrial , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/farmacologia
15.
Ren Fail ; 45(2): 2290179, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38059492

RESUMO

To determine the tip position of the central venous catheter (CVC) in patients with dialysis, the guidelines recommend that it be determined using chest radiography (CXR) after catheterization, without fluoroscopy. However, some researchers have proposed that transthoracic echocardiography (TTE) can replace CXR, but this has not been widely adopted. This study aimed to determine which of the two aforementioned methods is more suitable for locating the tip position of the CVC. This prospective study included 160 patients who underwent hemodialysis at our hospital from March 2021 to December 2022. After inserting the CVC through the internal jugular vein, we used transthoracic echocardiography and CXR to determine the tip of the CVC and compared the results with those of computed tomography (CT). In the comparison between TTE and CXR for locating the CVC tip, we obtained three main findings. (1) TTE was associated with fewer misdiagnosed cases than CXR. (2) TTE provided higher sensitivity (similar sensitivity in position 2), specificity, positive/negative predictive values, and accuracy than CXR. (3) When comparing the receiver operating characteristic curves of TTE and CXR, the area under the curve (95% confidence interval) for the former was larger. Additionally, we made anatomical discoveries: the "hyperechoic triangle" recognized by TTE was equivalent to the entrance of the superior vena cava into the right atrium shown by transesophageal transthoracic echocardiography. TTE is more suitable than CXR as the first examination for CVC tip localization, as it improves diagnostic accuracy and reduces X-ray radiation damage.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Humanos , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Cateteres Venosos Centrais/efeitos adversos , Ecocardiografia/métodos , Estudos Prospectivos , Diálise Renal/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Veia Cava Superior/diagnóstico por imagem , Raios X
16.
Entropy (Basel) ; 25(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38136531

RESUMO

Based on the NTRU trapdoor used in NIST's Falcon, a signcryption scheme following the sign-then-encrypt paradigm is constructed. The existing partitioning technique based on Waters hash over the lattice can not complete the security reduction in the standard model for the signature part due to the "partiality" of the pre-image generated with the NTRU trapdoor. To address this, a variant of Waters hash over small integers is proposed and, the probability of the successful reduction is analyzed. The resulting signcryption achieves existential unforgeability under the adaptive chosen-message attacks. By utilizing the uniqueness of the secret and the noise in an NTRU instance, the tag used in encryption is eliminated. Furthermore, a method to construct tamper-sensitive lattice public key encryption is proposed. This approach implants the ciphertext-sensitive information into the lattice public key encryption and binds it to the encrypted information. The malleability to the public key ciphertext triggers the change of the message-signature pair so that the IND-CCA2 security of the entire ciphertext can be guaranteed by the signature for the message. Thanks to the rational design and the efficiency of the NTRU trapdoor, the computational overhead of the proposed scheme is reduced significantly compared to the existing lattice-based signcryption scheme, reaching orders of magnitude improvement in efficiency. The experiment shows that the proposed scheme is efficient.

17.
ACS Appl Mater Interfaces ; 15(46): 53177-53188, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37939350

RESUMO

Gene therapy has great potential in treating neurodegenerative diseases with complex pathologies. The combination of small interfering RNAs (siRNAs) targeting ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) and caspase-3 will provide an effective treatment option for Alzheimer's disease (AD). To overcome the multiple physiological barriers and improve the therapeutic efficacy of siRNAs, lesion-recognizing nanoparticles (NPs) are constructed in this study for the synergistic treatment of AD. The lesion-recognizing NPs contain rabies virus glycoprotein peptide-modified mesenchymal stem cell-derived exosomes as the shell and a reactive oxygen species (ROS)-responsive polymer loaded with siRNAs as the core. After intranasal administration, the lesion-recognizing NPs cross the nasal mucosa and migrate to the affected brain areas. Furthermore, the NPs recognize the target cells and fuse with the cell membranes of neurons. The cores of NPs directly enter into the cytoplasm and achieve the controlled release of siRNAs in a high-ROS environment to downregulate the level of BACE1 and caspase-3 to ameliorate neurologic injury. In addition, lesion-recognizing NPs can significantly reduce the number of reactive astrocytes. Lesion-recognizing NPs have a positive effect on regulating the phase of neurons and astrocytes, which results in better restoration of memory deficits in 3 × Tg-AD mice. Therefore, this work provides a promising platform for neurodegenerative disease treatment.


Assuntos
Doença de Alzheimer , Nanopartículas , Doenças Neurodegenerativas , Camundongos , Animais , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/uso terapêutico , Caspase 3/genética , Caspase 3/metabolismo , RNA Interferente Pequeno/metabolismo , Doenças Neurodegenerativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/uso terapêutico , Encéfalo/metabolismo , Peptídeos beta-Amiloides/metabolismo
18.
BMC Sports Sci Med Rehabil ; 15(1): 127, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803353

RESUMO

BACKGROUND: Currently, technical and tactical analysis has become an indispensable task for sport in many countries. Many studies analysed players' specific technical and tactical factors, but it is rare to quantitatively analyse the importance of table tennis players' shot effectiveness. This is the first study to propose the new concept of "shot effectiveness model", and the purpose of this study is to explore the structure of the shot effectiveness model for elite table tennis, including the importance degree of shot effectiveness, and the relationship between them. METHODS: 258 matches were selected between the top 50 players in the world from 2019 to 2021 as samples. Multiple regression analysis was used to obtain the standard regression coefficients and game simulation, and the total decision coefficient (TDC) was used to evaluate the importance degrees of shot effectiveness (SE) on match results. RESULTS: (1) There was little difference in the importance degree of each shot effectiveness between men and women players. (2) The importance degree of the first and third shots (SE1), the second and fourth shots (SE2), the fifth and after shots (SE3), and the sixth and after shots (SE4) for both men and women players account for approximately 25%, 35%, 22%, and 16% respectively. (3) There was little difference in the importance degree of each shot effectiveness between Chinese women players and women players from other countries and regions with the same importance order of SE2 > SE1 > SE3 > SE4. However, the structure of the shot effectiveness model for men players was quite different from that for women players. (4) There is a compensation effect between shot effectiveness of table tennis players, and the total evaluation score of 12 and 13 is the dividing line for success or failure in both men and women matches. CONCLUSIONS: TDC could well reflect the important degrees of each shot effectiveness in various ways on winning probability in table tennis matches. And this study compared the importance of several types of players' performance on the probability of winning a match. In addition, we found that there is a compensation effect between shot effectiveness of table tennis players, and the magnitude of this effect will vary according to the type and level of shot effectiveness.

19.
J Agric Food Chem ; 71(44): 16727-16738, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37871231

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is frequently used as a plasticizer in industrial and agricultural products. DEHP can cause severe neurotoxicity, such as impaired learning and memory function. Lycopene (LYC) as a carotenoid exerts excellent antioxidant capacity and therapeutic effects in neurodegenerative diseases. However, whether LYC can prevent the cognitive impairment induced by DEHP and the specific mechanisms are unclear. In the present study, the behavioral test results suggested that LYC alleviated the learning and memory impairment induced by DEHP. The histopathological data revealed that LYC attenuated DEHP-induced disordered arrangement of the neurons in the CA1 and CA3 regions of the hippocampus tissue. Moreover, LYC inhibited the occurrence of DEHP-induced ferroptosis via regulating iron metabolism, inhibiting lipid peroxidation, and activating the cysteine transporter and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (NrF2/HO-1) signaling pathway. Overall, the study contributes novel perspectives into the potential mechanisms of LYC preventing phthalate-induced cognitive impairment in the hippocampus.


Assuntos
Disfunção Cognitiva , Dietilexilftalato , Ferroptose , Humanos , Licopeno/metabolismo , Estresse Oxidativo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/tratamento farmacológico
20.
iScience ; 26(10): 107870, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37766973

RESUMO

Even though the discovery of lytic polysaccharide monooxygenases (LPMOs) has fundamentally shifted our understanding of biomass degradation, most of the current studies focused on their roles in carbohydrate oxidation. However, no study demonstrated if LPMO could directly participate to the process of lignin degradation in lignin-degrading microbes. This study showed that LPMO could synergize with lignin-degrading enzymes for efficient lignin degradation in white-rot fungi. The transcriptomics analysis of fungi Irpex lacteus and Dichomitus squalens during their lignocellulosic biomass degradation processes surprisingly highlighted that LPMOs co-regulated with lignin-degrading enzymes, indicating their more versatile roles in the redox network. Biochemical analysis further confirmed that the purified LPMO from I. lacteus CD2 could use diverse electron donors to produce H2O2, drive Fenton reaction, and synergize with manganese peroxidase for lignin oxidation. The results thus indicated that LPMO might uniquely leverage the redox network toward dynamic and efficient degradation of different cell wall components.

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