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1.
Plants (Basel) ; 13(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39273899

RESUMEN

As an important part of heat shock response module, heat shock proteins (HSP) play an important role in plant defense response against heat stress; however, the involvement of the majority of the HSP family members against other abiotic stresses remains poorly understood. In the present study, LrHSP17.2 was identified and its function against abiotic stress was analyzed. The expression level of LrHSP17.2 was significantly induced by heat. Heterologous transgenes of LrHSP17.2 showed that LrHSP17.2 can increase the activity of catalase, peroxidase, superoxide dismutase to removes excess reactive oxygen species (ROS), maintain the stability of the membrane structure, and regulate genes related to antioxidant enzymes and defense under abiotic stress. In addition, LrHSP17.2 could be regulated by exogenous abscisic acid and melatonin, and the related hormone synthesis genes of transgenic plants were significantly up-regulated under heat stress. Taken together, our results revealed that LrHSP17.2 is involved in regulating abiotic stress responses by regulating ROS scavenging and stress-related genes in Lilium regale.

2.
Biomed Environ Sci ; 37(4): 354-366, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38727158

RESUMEN

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.


Asunto(s)
Inflamación , Mercurio , Fosfohidrolasa PTEN , Humanos , Regulación hacia Abajo , Células HEK293 , Inflamación/inducido químicamente , Inflamación/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/sangre , Mercurio/toxicidad , Exposición Profesional/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal/efectos de los fármacos
3.
Adv Mater ; 36(25): e2314271, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38569202

RESUMEN

Transition metal chalcogenides (TMCs) emerge as promising anode materials for sodium-ion batteries (SIBs), heralding a new era of energy storage solutions. Despite their potential, the mechanisms underlying their performance enhancement and susceptibility to failure in ether-based electrolytes remain elusive. This study delves into these aspects, employing CoS2 electrodes as a case in point to elucidate the phenomena. The investigation reveals that CoS2 undergoes a unique irreversible and progressive solid-liquid-solid phase transition from its native state to sodium polysulfides (NaPSs), and ultimately to a Cu1.8S/Co composite, accompanied by a gradual morphological transformation from microspheres to a stable 3D porous architecture. This reconstructed 3D porous structure is pivotal for its exceptional Na+ diffusion kinetics and resilience to cycling-induced stress, being the main reason for ultrastable cycling and ultrahigh rate capability. Nonetheless, the CoS2 electrode suffers from an inevitable cycle life termination due to the microshort-circuit induced by Na metal corrosion and separator degradation. Through a comparative analysis of various TMCs, a predictive framework linking electrode longevity is established to electrode potential and Gibbs free energy. Finally, the cell failure issue is significantly mitigated at a material level (graphene encapsulation) and cell level (polypropylene membrane incorporation) by alleviating the NaPSs shuttling and microshort-circuit.

4.
Sci Rep ; 14(1): 538, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38177652

RESUMEN

Dynamic network link prediction is extensively applicable in various scenarios, and it has progressively emerged as a focal point in data mining research. The comprehensive and accurate extraction of node information, as well as a deeper understanding of the temporal evolution pattern, are particularly crucial in the investigation of link prediction in dynamic networks. To address this issue, this paper introduces a node representation learning framework based on Graph Convolutional Networks (GCN), referred to as GCN_MA. This framework effectively combines GCN, Recurrent Neural Networks (RNN), and multi-head attention to achieve comprehensive and accurate representations of node embedding vectors. It aggregates network structural features and node features through GCN and incorporates an RNN with multi-head attention mechanisms to capture the temporal evolution patterns of dynamic networks from both global and local perspectives. Additionally, a node representation algorithm based on the node aggregation effect (NRNAE) is proposed, which synthesizes information including node aggregation and temporal evolution to comprehensively represent the structural characteristics of the network. The effectiveness of the proposed method for link prediction is validated through experiments conducted on six distinct datasets. The experimental outcomes demonstrate that the proposed approach yields satisfactory results in comparison to state-of-the-art baseline methods.

5.
J Ethnopharmacol ; 321: 117560, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38081396

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Dauricine (DA) is a natural plant-derived alkaloid extracted from Menispermum dauricum. Menispermum dauricum has been used in traditional Chinese medicine as a classic remedy for rheumatoid arthropathy and is believed to be effective in alleviating swelling and pain in the limbs. AIM OF THE STUDY: Osteoarthritis (OA) is a classic degenerative disease involving chondrocyte death, and there is still a lack of effective therapeutic agents that can reverse the progression of the disease. Here we explored the therapeutic effects of DA against OA and further explored the mechanism. MATERIALS AND METHODS: The effect of DA on cell viability was assessed by CCK-8. IL-1ß-treated mouse chondrocytes were used as an in vitro model of OA, and apoptosis was detected by flow cytometry. QRT-PCR, western blotting, cell staining, and immunofluorescence were used to detect relevant inflammatory factors and cartilage-specific expression. RNA sequencing was used to identify pertinent signaling pathways. The therapeutic effect of DA was verified by micro-CT, histological analysis and immunohistochemical analysis in a mouse OA model. RESULTS: DA demonstrated a high safety profile on chondrocytes, significantly reversing the inflammatory response induced by IL-1ß, and promoting factors associated with cartilage regeneration. Moreover, DA exhibited a significant protective effect on the knee joints of mice undergoing ACLT-DMM, effectively preventing cartilage degeneration and subchondral bone tissue destruction. These positive therapeutic effects were achieved through the modulation of the NF-κB pathway and the Ca2+ signaling pathway by DA. CONCLUSION: Being derived from a traditional herb, DA exhibits remarkable therapeutic potential and safety in OA treatment, presenting a promising option for patients dealing with osteoarthritis.


Asunto(s)
Bencilisoquinolinas , Menispermum , Osteoartritis , Humanos , Ratones , Animales , FN-kappa B/metabolismo , Condrocitos , Menispermum/metabolismo , Células Cultivadas , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Bencilisoquinolinas/farmacología , Osteoartritis/inducido químicamente , Osteoartritis/tratamiento farmacológico , Interleucina-1beta/metabolismo
6.
Adv Sci (Weinh) ; 11(4): e2305890, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38039434

RESUMEN

Biomaterials encounter considerable challenges in extensive bone defect regeneration. The amelioration of outcomes may be attainable through the orchestrated modulation of both innate and adaptive immunity. Silicon-hydroxyapatite, for instance, which solely focuses on regulating innate immunity, is inadequate for long-term bone regeneration. Herein, extra manganese (Mn)-doping is utilized for enhancing the osteogenic ability by mediating adaptive immunity. Intriguingly, Mn-doping engenders heightened recruitment of CD4+ T cells to the bone defect site, concurrently manifesting escalated T helper (Th) 2 polarization and an abatement in Th1 cell polarization. This consequential immune milieu yields a collaborative elevation of interleukin 4, secreted by Th2 cells, coupled with attenuated interferon gamma, secreted by Th1 cells. This orchestrated interplay distinctly fosters the osteogenesis of bone marrow stromal cells and effectuates consequential regeneration of the mandibular bone defect. The modulatory mechanism of Th1/Th2 balance lies primarily in the indispensable role of manganese superoxide dismutase (MnSOD) and the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). In conclusion, this study highlights the transformative potential of Mn-doping in amplifying the osteogenic efficacy of silicon-hydroxyapatite nanowires by regulating T cell-mediated adaptive immunity via the MnSOD/AMPK pathway, thereby creating an anti-inflammatory milieu favorable for bone regeneration.


Asunto(s)
Nanocables , Osteogénesis , Manganeso/farmacología , Silicio/farmacología , Durapatita/farmacología , Proteínas Quinasas Activadas por AMP/farmacología
7.
Sci Data ; 10(1): 790, 2023 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-37949921

RESUMEN

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of bioactive lipids that show therapeutic potential for diabetes, anti-cancer and inflammation. These FAHFAs can be obtained through dietary intake, potentially improving human health. However, there is currently inadequate knowledge regarding the presence and variety of FAHFAs in different foods. Herein, we profile FAHFAs from 12 typical food samples and 4 medicinal food samples with the aid of our previous established chemical isotope labeling-assisted liquid chromatography-mass spectrometry method and build a comprehensive dataset of FAHFA diversity. The dataset comprised a total of 1207 regioisomers belonging to 298 different families, with over 100 families being newly discovered for the first time. Therefore, our findings contribute valuable insights into the molecular diversity and presence of FAHFA in a range of foods. This dataset serves as a foundation for further exploration of the nutritional and medicinal functions of FAHFAs.


Asunto(s)
Ésteres , Ácidos Grasos , Humanos , Cromatografía Liquida/métodos , Ésteres/análisis , Ésteres/química , Alimentos , Espectrometría de Masas
8.
Adv Healthc Mater ; 12(32): e2302054, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37842937

RESUMEN

Silicon (Si)-based biomaterials are widely applied for bone regeneration. However, the underlying mechanisms of the materials function remain largely unknown. T lymphocyte-mediated adaptive immune response plays a vital role in the process of bone regeneration. In the current study, mesoporous silica (MS) is used as a model material of Si-based biomaterials. It shows that the supernatant of CD4+ T lymphocytes pretreated with MS extract significantly promotes the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract can reduce the expression of regulatory factor X-1 (RFX-1) in CD4+ T lymphocytes. This may result in the overexpression of interleukin-17A (IL-17A) by boosting histone H3 acetylation and lowering DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further reveal that MS particles significantly enhance bone regeneration with improved angiogenesis in the critical-sized calvarial defect mouse model accompanied by upregulation of IL-17A in peripheral blood and the proportion of Th17 cells. This study suggests that modulation of the adaptive immune response of T lymphocytes by silicate-based biomaterials plays an important role for bone regeneration.


Asunto(s)
Osteogénesis , Silicio , Ratones , Animales , Silicio/farmacología , Materiales Biocompatibles/farmacología , Interleucina-17 , Epigénesis Genética , Angiogénesis , Linfocitos T , Regeneración Ósea , Dióxido de Silicio/farmacología , Inmunidad Adaptativa
9.
J Neurochem ; 2023 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-37804203

RESUMEN

Significant evidence suggests that misfolded alpha-synuclein (aSyn), a major component of Lewy bodies, propagates in a prion-like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha-synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human-relevant cognitive and structural neuroanatomical measures is not fully understood. Here we performed a single unilateral striatal PFF injection in M83 hemizygous mice, and using two assays with translational potential, ex vivo magnetic resonance imaging (MRI) and touchscreen testing, we examined the combined neuroanatomical and behavioral impact of aSyn propagation. In PFF-injected mice, we observed widespread atrophy in bilateral regions that project to or receive input from the injection site using MRI. We also identified early deficits in reversal learning prior to the emergence of motor symptoms. Our findings highlight a network of regions with related cellular correlates of pathology that follow the progression of aSyn spreading, and that affect brain areas relevant for reversal learning. Our experiments suggest that M83 hemizygous mice injected with human PFF provides a model to understand how misfolded aSyn affects human-relevant pre-clinical measures and suggest that these pre-clinical biomarkers could be used to detect early toxicity of aSyn and provide better translational measures between mice and human disease.

10.
Chemosphere ; 335: 139169, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37295682

RESUMEN

The discovery of comammox Nitrospira, a complete ammonia-oxidizing microorganism belonging to the genus Nitrospira, has brought new insights into the nitrification process in wastewater treatment plants (WWTPs). The applicability of Activated Sludge Model No. 2 d with one-step nitrification (ASM2d-OSN) or two-step nitrification (ASM2d-TSN) for the simulation of the biological nutrient removal (BNR) processes of a full-scale WWTP in the presence of comammox Nitrospira was studied. Microbial analysis and kinetic parameter measurements showed comammox Nitrospira was enriched in the BNR system operated under low dissolved oxygen (DO) and long sludge retention time (SRT). The relative abundance of Nitrospira under the conditions of stage I (DO = 0.5 mg/L, SRT = 60 d) was about twice of that under stage II conditions (DO = 4.0 mg/L, SRT = 26 d), and the copy number of the comammox amoA gene for stage I was 33 times higher than that for stage II. Compared to the ASM2d-OSN model, the ASM2d-TSN model simulated the performance of the WWTP under stage I conditions better, and the Theil inequality coefficient values of all the tested water quality parameters were lower than using ASM2d-OSN. These results indicate that an ASM2d model with two-step nitrification is a better choice for the simulation of WWTPs with the presence of comammox.


Asunto(s)
Betaproteobacteria , Nitrificación , Amoníaco , Aguas del Alcantarillado , Oxidación-Reducción , Bacterias/genética , Oxígeno , Filogenia , Archaea
11.
J Mater Chem B ; 11(20): 4396-4407, 2023 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-37158364

RESUMEN

The osteogenic function of mesenchymal stem cells (MSCs) is mainly attributed to the paracrine effect of extracellular vesicles. MSC-derived exosomes are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials, and have emerged as cell-free regenerative medicine in recent years. In this study, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were loaded with photothermal material layered black phosphorus (BP) modified poly(N-isopropylacrylamide) (PNIPAAm) thermosensitive hydrogels to explore their effects on bone defect repair. In vitro, it was confirmed that the local high heat of nano-BP irradiated using a near-infrared (NIR) laser could trigger the reversible cascade reaction of hydrogels, and that the mechanical contraction of hydrogels led to the controllable release of a large number of exosomes along with the release of water molecules. Furthermore, in vitro investigations demonstrated that BP hydrogels loaded with BMSC-derived exosomes had favourable biocompatibility and could promote the proliferation and osteogenic differentiation of MSCs. Experiments conducted in vivo confirmed that this system significantly promoted bone regeneration. Therefore, the results of our study indicated that the nanoplatform based on BP thermosensitive hydrogels could provide a new clinical treatment strategy for controlled release and on-demand drug delivery, while the cell-free system composed of BMSC-derived exosomes had great application potential in bone tissue repair with the synergism of BP.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Osteogénesis , Hidrogeles/farmacología , Huesos
12.
Anal Chim Acta ; 1239: 340691, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36628759

RESUMEN

Bile acids (BAs) are a class of vital gut microbiota-host cometabolites, and they play an important role in maintaining gut microbiota-host metabolic homeostasis. Very recently, a new mechanism of BA anabolic metabolism mediated by gut microbiota (BA-amino acid conjugation) has been revealed, which provides a perspective for the research on BA metabolism and gut metabolome. In this study, we established a polarity-switching multiple reaction monitoring mass spectrometry-based screening method to mine amino acid-conjugated bile acids (AA-BAs) derived from host-gut microbiota co-metabolism. In addition, a retention time-based annotation strategy was further proposed to identify the AA-BA isomers and epimers. Using the developed methods, we successfully screened 118 AA-BA conjugates from mouse and human feces, 28 of them were confirmed by standards, and 62 putatively identified based on their predicted retention times. Moreover, we observed that the levels of most AA-BAs were significantly downregulated in the feces of chronic sleep deprivation mice, suggesting that the AA-BA metabolism was closely related to the physiological state of the host.


Asunto(s)
Aminoácidos , Ácidos y Sales Biliares , Ratones , Humanos , Animales , Aminoácidos/análisis , Cromatografía Liquida , Espectrometría de Masas , Ácidos y Sales Biliares/análisis , Heces/química
13.
Vaccines (Basel) ; 10(12)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36560475

RESUMEN

The current influenza vaccines only confer protection against the circulating influenza subtypes, therefore universal vaccines are needed to prevent upcoming influenza outbreaks caused by emerging influenza subtypes. The extracellular domain of influenza A M2 protein (M2e) is highly conserved among different subtypes of influenza A viruses, and it is able to elicit protective immunity against the viruses. The influenza nucleoprotein (NP) was used to display the M2e in this study due to its promising T-cell response and adjuvanticity. The M2e gene was fused to the 5'-end of the NP gene and then cloned into pRSET B vector. The DNA sequencing analysis revealed six point mutations in the M2e-NP fusion gene, including one mutation in the M2e peptide and five mutations in the NP. The mutations were reverted using PCR site-directed mutagenesis. The recombinant plasmids (pRSET B-M2e-NP and pRSET B-mM2e-NP) were introduced into Escherichia coli (E. coli) BL21 (DE3) for protein expression. The mutated and non-mutated proteins were subsequently expressed and named mM2e-NP and M2e-NP, respectively. The expression of mM2e-NP and M2e-NP was not affected by the mutations. The binding of anti-M2e antibody to the purified native mM2e-NP and M2e-NP also remained active. However, when the anti-NP antibody was tested, the signal produced by mM2e-NP was very weak. The results implied that the amino acid changes in the NP had adversely impacted on the conformation of mM2e-NP and subsequently affected the antibody binding. In light of the remarkable antibody binding to the M2e-NP fusion protein, this study highly recommends the potential of M2e-NP as a universal influenza vaccine candidate.

14.
Sensors (Basel) ; 22(23)2022 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-36502177

RESUMEN

The state-of-energy (SOE) and state-of-health (SOH) are two crucial quotas in the battery management systems, whose accurate estimation is facing challenges by electric vehicles' (EVs) complexity and changeable external environment. Although the machine learning algorithm can significantly improve the accuracy of battery estimation, it cannot be performed on the vehicle control unit as it requires a large amount of data and computing power. This paper proposes a joint SOE and SOH prediction algorithm, which combines long short-term memory (LSTM), Bi-directional LSTM (Bi-LSTM), and convolutional neural networks (CNNs) for EVs based on vehicle-cloud collaboration. Firstly, the indicator of battery performance degradation is extracted for SOH prediction according to the historical data; the Bayesian optimization approach is applied to the SOH prediction combined with Bi-LSTM. Then, the CNN-LSTM is implemented to provide direct and nonlinear mapping models for SOE. These direct mapping models avoid parameter identification and updating, which are applicable in cases with complex operating conditions. Finally, the SOH correction in SOE estimation achieves the joint estimation with different time scales. With the validation of the National Aeronautics and Space Administration battery data set, as well as the established battery platform, the error of the proposed method is kept within 3%. The proposed vehicle-cloud approach performs high-precision joint estimation of battery SOE and SOH. It can not only use the battery historical data of the cloud platform to predict the SOH but also correct the SOE according to the predicted value of the SOH. The feasibility of vehicle-cloud collaboration is promising in future battery management systems.


Asunto(s)
Suministros de Energía Eléctrica , Electricidad , Estados Unidos , Teorema de Bayes , Fenómenos Físicos , Redes Neurales de la Computación
15.
Shanghai Kou Qiang Yi Xue ; 31(3): 225-231, 2022 Jun.
Artículo en Chino | MEDLINE | ID: mdl-36204947

RESUMEN

PURPOSE: To investigate the effect of tension on the inflammatory response of human periodontal ligament cells (PDLCs) induced by isoproterenol (ISO) and its molecular mechanism. METHODS: Human PDLCs were cultured in vitro and stimulated with a certain concentration of ISO(0.01, 0.1, 1 µmol/L) for 24 h. Cyclic tensile strain with different degrees of elongation (5%, 10% and 15%) were applied. The expression of IL-1ß and IL-6 mRNA in PDLCs was detected by real-time quantitative PCR(RT-qPCR). The protein expression of p-PERK, PERK, p-eIF2α, eIF2α and ATF4 related to ER stress was detected by Western blot. The expression of PERK gene in PDLCs was knocked down by cell transfection technique, and the expression of IL-1ß and IL-6 mRNA in PDLCs with low expression of PERK was detected by RT-qPCR under the stimulation of ISO and low magnitude tension. Statistical analysis was conducted with SPSS 22.0 software package. RESULTS: ISO induction could significantly up-regulate the IL-1ß and IL-6 mRNA expression in PDLCs(P<0.05). Compared with the control group, the expression of IL-1ß and IL-6 mRNA in PDLCs induced by ISO was inhibited by low magnitude tension, and the difference was statistically significant(P<0.05). Western blot results showed that low magnitude tension could inhibit the ISO-stimulated phosphorylation of PERK and eIF2α and the expression of ATF4(P<0.05). Compared with the negative control group, IL-1ß and IL-6 mRNA expression was decreased in the ISO-stimulated PDLCs silenced by PERK gene. CONCLUSIONS: Tension with 5% degrees of elongation may inhibit ISO-stimulated periodontal inflammatory response through endoplasmic reticulum stress pathway.


Asunto(s)
Interleucina-6 , Ligamento Periodontal , Células Cultivadas , Estrés del Retículo Endoplásmico , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Isoproterenol/metabolismo , Isoproterenol/farmacología , Ligamento Periodontal/metabolismo , ARN Mensajero/metabolismo
16.
Acta Neuropathol ; 144(5): 881-910, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36121476

RESUMEN

The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). Molecular chaperones play important roles in protein misfolding diseases and members of the chaperone machinery are often deposited in Lewy bodies. Here, we show that the Hsp90 co-chaperone STI1 co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in insoluble protein fractions in two mouse models of α-synuclein misfolding. STI1 and Hsp90 also co-localized extensively with filamentous S129 phosphorylated α-synuclein in ubiquitin-positive inclusions. In PD human brains, STI1 transcripts were increased, and in neurologically healthy brains, STI1 and α-synuclein transcripts correlated. Nuclear Magnetic Resonance (NMR) analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein. In vitro, the STI1 TPR2A domain facilitated S129 phosphorylation by Polo-like kinase 3. Moreover, mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils. In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice. Our findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90.


Asunto(s)
Proteínas de Choque Térmico/metabolismo , Proteínas Intrínsecamente Desordenadas , alfa-Sinucleína/metabolismo , Animales , Proteínas HSP90 de Choque Térmico/química , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Ratones , Chaperonas Moleculares/metabolismo , Fosfoproteínas , Ubiquitinas , alfa-Sinucleína/toxicidad
17.
J Trace Elem Med Biol ; 74: 127057, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35969986

RESUMEN

BACKGROUND: circRNAs have been recognized as biomarkers of numerous diseases. We would like to explore the expression pattern and molecular mechanisms of circRNAs in the Chinese occupational mercury-exposed population. METHODS: The workers from a thermometer manufacturing plant and lamp factory in Jiangsu province of China were recruited in 2016. Blood samples were collected from the subjects with chronic mercury poisoning group, mercury absorption group, and the healthy controls. The differentially expressed circRNAs (DECRs) between the three groups were screened from serum samples using a circRNA microarray. The significant DECRs were validated by qRT-PCR, and their respective diagnostic values for mercury poisoning and mercury absorption were analyzed by receiver operating characteristic (ROC) curves. For in vitro experiments, 293T cells were treated with different doses of HgCl2 to determine the half-lethal concentration. The cells were transfected with the siRNA construct or expression plasmid of circRNA. The expression levels of JNK, p38, and caspase family proteins were analyzed by Western blotting. RESULTS: hsa_circ_0025244 was up-regulated in the mercury poisoning and absorption groups compared to the control group (P < 0.05), and positively correlated with the urine mercury levels (P < 0.05). The area under the ROC curve (AUC) of hsa_circ_0025244 for diagnosing occupational mercury poisoning was 0.748, indicating moderate accuracy (P < 0.001). Moreover, the diagnostic accuracy of occupational mercury absorption was high (P < 0.001) with an AUC of 0.918. Knockdown of hsa_circ_0025244 in 293T cells significantly reduced the expression levels of JNK/p38, and caspase family proteins compared to that in the control cells (P < 0.01), and its overexpression led to opposite effects (P < 0.05). CONCLUSIONS: hsa_circ_0025244 is a potential biomarker for mercury exposure and mediates mercury-induced apoptosis in 293T cells by activating the JNK/p38 MAPK signaling pathway.


Asunto(s)
Intoxicación por Mercurio , Mercurio , Apoptosis , Biomarcadores , Caspasas/metabolismo , Humanos , ARN Circular/genética , ARN Interferente Pequeño , Curva ROC , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
18.
Environ Sci Pollut Res Int ; 29(48): 73282-73291, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35619014

RESUMEN

CdS-based composites as the highly efficient photocatalyst have been extensively investigated in recent years due to the suitable band gap and high photocatalytic efficiency. In this study, the effect of various factors (pH, U(VI) concentration, contents, and types of photocatalyst) on photocatalytic reduction of U(VI) by MoS2/CdS composite was investigated. The optimized experimental conditions (e.g., pH 7.0, 20 mg/g U(VI), and 1.0 g/L photocatalyst) was obtained by batch techniques. Approximately 97.5% of U(VI) was photo-catalytically reduced into U(IV) by 2.5 wt% MoS2/CdS composite within 15 min. After 5 cycles, 2.5 wt% MoS2/CdS composite still exhibited the high removal efficiency of U(VI) under 50-min irradiation, indicating the good stability. The photo-reduction mechanism of U(VI) on MoS2/CdS composite was attributed to the O-2 radicals by quenching experiments, ESR, and XPS analysis. The findings indicate that CdS-based catalyst has a great potential for the photocatalytic reduction of uranyl in actual environmental remediation.


Asunto(s)
Restauración y Remediación Ambiental , Molibdeno , Catálisis , Molibdeno/química
19.
J Nanobiotechnology ; 20(1): 162, 2022 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-35351145

RESUMEN

BACKGROUND: The repair of tissue defects has attracted considerable attention and remained a substantial challenge. Calcium silicate (CaSiO3, CS) bioceramics have attracted the interest of researchers due to their excellent biodegradability. Recent studies have demonstrated that nanoscale-modified bioactive materials with favorable biodegradability could promote bone tissue regeneration, providing an alternative approach for the repair of bone defects. However, the direct construction of biodegradable nanostructures in situ on CS bioceramics was still difficult. RESULTS: In this study, flower-like nanostructures were flexibly prepared in situ on biodegradable CS bioceramics via hydrothermal treatment. The flower-like nanostructure surfaces exhibited better hydrophilicity and more significantly stimulated cell adhesion, alkaline phosphatase (ALP) activity, and osteogenic differentiation. Furthermore, the CS bioceramics with flower-like nanostructures effectively promoted bone regeneration and were gradually replaced with newly formed bone due to the favorable biodegradability of these CS bioceramics. Importantly, we revealed an osteogenesis-related mechanism by which the FAK/p38 signaling pathway could be involved in the regulation of bone mesenchymal stem cell (BMSC) osteogenesis by the flower-like nanostructure surfaces. CONCLUSIONS: Flower-like nanostructure surfaces on CS bioceramics exerted a strong effect on promoting bone repair and regeneration, suggesting their excellent potential as bone implant candidates for improving bone regeneration.


Asunto(s)
Nanoestructuras , Osteogénesis , Regeneración Ósea , Compuestos de Calcio , Transducción de Señal , Silicatos
20.
Anal Chem ; 94(5): 2655-2664, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35085440

RESUMEN

Bile acids (BAs) are a type of gut microbiota-host cometabolites with abundant structural diversity, and they play critical roles in maintaining host-microbiota homeostasis. In this study, we developed a new N-(4-aminomethylphenyl) pyridinium (AMPP) derivatization-assisted alternating dual-collision energy scanning mass spectrometry (AMPP-dual-CE MS) method for the profiling of BAs derived from host-gut microbiota cometabolism in mice. Using the proposed method, we discovered two new types of amino acid conjugations (alanine conjugation and proline conjugation) and acetyl conjugation with host BAs, for the first time, from mouse intestine contents and feces. Additionally, we also determined and identified nine new leucine- and phenylalanine-conjugated BAs. These findings broaden our knowledge of the composition of the BA pool and provide insight into the mechanism of host-gut microbiota cometabolism of BAs.


Asunto(s)
Ácidos y Sales Biliares , Microbioma Gastrointestinal , Animales , Bilis , Ácidos y Sales Biliares/análisis , Heces/química , Espectrometría de Masas , Ratones
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