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1.
Biomed Environ Sci ; 37(4): 354-366, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727158

RESUMO

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.


Assuntos
Regulação para Baixo , Inflamação , Mercúrio , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mercúrio/toxicidade , Transdução de Sinais/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Células HEK293 , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/sangue
2.
Adv Mater ; : e2314271, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569202

RESUMO

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.

3.
Sci Rep ; 14(1): 538, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177652

RESUMO

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.

4.
J Ethnopharmacol ; 321: 117560, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38081396

RESUMO

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.


Assuntos
Benzilisoquinolinas , Menispermum , Osteoartrite , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Condrócitos , Menispermum/metabolismo , Células Cultivadas , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Benzilisoquinolinas/farmacologia , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Interleucina-1beta/metabolismo
5.
Adv Sci (Weinh) ; 11(4): e2305890, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039434

RESUMO

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.


Assuntos
Nanofios , Osteogênese , Manganês/farmacologia , Silício/farmacologia , Durapatita/farmacologia , Proteínas Quinases Ativadas por AMP/farmacologia
6.
Sci Data ; 10(1): 790, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949921

RESUMO

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.


Assuntos
Ésteres , Ácidos Graxos , Humanos , Cromatografia Líquida/métodos , Ésteres/análise , Ésteres/química , Alimentos , Espectrometria de Massas
7.
J Neurochem ; 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37804203

RESUMO

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.

8.
Adv Healthc Mater ; 12(32): e2302054, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37842937

RESUMO

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.


Assuntos
Osteogênese , Silício , Camundongos , Animais , Silício/farmacologia , Materiais Biocompatíveis/farmacologia , Interleucina-17 , Epigênese Genética , Angiogênese , Linfócitos T , Regeneração Óssea , Dióxido de Silício/farmacologia , Imunidade Adaptativa
9.
Chemosphere ; 335: 139169, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37295682

RESUMO

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.


Assuntos
Betaproteobacteria , Nitrificação , Amônia , Esgotos , Oxirredução , Bactérias/genética , Oxigênio , Filogenia , Archaea
10.
J Mater Chem B ; 11(20): 4396-4407, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37158364

RESUMO

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.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Osteogênese , Hidrogéis/farmacologia , Osso e Ossos
11.
Anal Chim Acta ; 1239: 340691, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628759

RESUMO

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.


Assuntos
Aminoácidos , Ácidos e Sais Biliares , Camundongos , Humanos , Animais , Aminoácidos/análise , Cromatografia Líquida , Espectrometria de Massas , Ácidos e Sais Biliares/análise , Fezes/química
12.
International Eye Science ; (12): 913-917, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973776

RESUMO

Demodex is one of the most common parasites in the human body. It can be classified into demodex folliculorum and demodex brevis based on the parasitic sites. It is an opportunistic pathogenic microorganism, and clinical symptoms may not appear in part of infected people, but the parasite can cause multiple common ocular diseases represented by blepharitis. Its typical symptoms include dry eyes, foreign body sensation in eyes, secretion attached to eyelashes, and ocular surface irritation. The diagnosis of demodex blepharitis should be based on the clinical manifestations and the results of etiological tests. The treatment is related to many kinds of drugs including plant essential oil and physical therapy. At present, diagnosing and treating demodex blepharitis is increasingly sophisticated, but the relationship between demodex infection and its pathogenicity remains unclear. This paper summarizes the current characteristics of demodex and the clinical manifestation, diagnosis, treatment, and existing issues of demodex blepharitis, hoping to provide a reference for future studies in demodex.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970596

RESUMO

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.


Assuntos
Espectrometria de Massas em Tandem , Farmacologia em Rede , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Tecnologia
14.
Vaccines (Basel) ; 10(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36560475

RESUMO

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.

15.
Sensors (Basel) ; 22(23)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36502177

RESUMO

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.


Assuntos
Fontes de Energia Elétrica , Eletricidade , Estados Unidos , Teorema de Bayes , Fenômenos Físicos , Redes Neurais de Computação
16.
Shanghai Kou Qiang Yi Xue ; 31(3): 225-231, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-36204947

RESUMO

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.


Assuntos
Interleucina-6 , Ligamento Periodontal , Células Cultivadas , Estresse do Retículo Endoplasmático , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Ligamento Periodontal/metabolismo , RNA Mensageiro/metabolismo
17.
Acta Neuropathol ; 144(5): 881-910, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36121476

RESUMO

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.


Assuntos
Proteínas de Choque Térmico/metabolismo , Proteínas Intrinsicamente Desordenadas , alfa-Sinucleína/metabolismo , Animais , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Camundongos , Chaperonas Moleculares/metabolismo , Fosfoproteínas , Ubiquitinas , alfa-Sinucleína/toxicidade
18.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22280475

RESUMO

Background and AimsResearch suggests that many individuals infected with COVID-19 experience changes in taste and smell that can persist for months after the initial infection. These sensory changes can potentially have long-term impacts on dietary choices, nutrition, and body weight. The aim of this study is to explore COVID-related changes in dietary intake among University Students. MethodsA retrospective cohort design will be used to compare a cohort of University Students who experienced COVID-19 infection versus pre-existing data collected from a similar cohort prior to the pandemic. Specifically, the pre-existing data were collected between July 2017 and July 2021. Both datasets comprise of a weighed Food Record and Dutch Eating Behaviour Questionnaire. The cohort will also be asked about their experience with COVID-19 and changes in their eating behaviour since before the pandemic. Total daily energy intake, macronutrient intake and composition, will be compared across groups using an ANCOVA analysis controlling for age, gender, and ethnicity. DiscussionUnderstanding the long-term impact of COVID-19 infection is crucial. While COVID-related sensory changes are hypothesised to have impacts on eating behaviour and dietary choices, it is challenging to perform controlled cohort studies due to the high prevalence of undetected infections. The proposed temporal analyses provide a unique opportunity to test for COVID-related impacts on eating behaviour.

19.
J Trace Elem Med Biol ; 74: 127057, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35969986

RESUMO

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.


Assuntos
Intoxicação por Mercúrio , Mercúrio , Apoptose , Biomarcadores , Caspases/metabolismo , Humanos , RNA Circular/genética , RNA Interferente Pequeno , Curva ROC , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Environ Sci Pollut Res Int ; 29(48): 73282-73291, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35619014

RESUMO

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.


Assuntos
Recuperação e Remediação Ambiental , Molibdênio , Catálise , Molibdênio/química
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