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1.
Nat Commun ; 15(1): 5713, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977661

RESUMO

Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.


Assuntos
Senescência Celular , Guanosina , Metiltransferases , Biossíntese de Proteínas , RNA de Transferência , Senescência Celular/genética , RNA de Transferência/metabolismo , RNA de Transferência/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Guanosina/análogos & derivados , Guanosina/metabolismo , Metilação , Humanos , Ribossomos/metabolismo , Envelhecimento/metabolismo , Envelhecimento/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Animais , Fator 1 de Elongação de Peptídeos/metabolismo , Fator 1 de Elongação de Peptídeos/genética , Estabilidade de RNA
2.
Molecules ; 29(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998982

RESUMO

In this research, the authors studied the synthesis of a silicon-based quaternary ammonium material based on the coupling agent chloromethyl trimethoxysilane (KH-150) as well as its adsorption and separation properties for Th(IV). Using FTIR and NMR methods, the silicon-based materials before and after grafting were characterized to determine the spatial structure of functional groups in the silicon-based quaternary ammonium material SG-CTSQ. Based on this, the functional group grafting amount (0.537 mmol·g-1) and quaternization rate (83.6%) of the material were accurately calculated using TGA weight loss and XPS. In the adsorption experiment, the four materials with different grafting amounts showed different degrees of variation in their adsorption of Th(IV) with changes in HNO3 concentration and NO3- concentration but all exhibited a tendency toward anion exchange. The thermodynamic and kinetic experimental results demonstrated that materials with low grafting amounts (SG-CTSQ1 and SG-CTSQ2) tended to physical adsorption of Th(IV), while the other two tended toward chemical adsorption. The adsorption mechanism experiment further proved that the functional groups achieve the adsorption of Th(IV) through an anion-exchange reaction. Chromatographic column separation experiments showed that SG-CTSQ has a good performance in U-Th separation, with a decontamination factor for uranium in Th(IV) of up to 385.1, and a uranium removal rate that can reach 99.75%.

3.
Int J Biol Macromol ; 275(Pt 2): 133601, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969031

RESUMO

Fatigue is a common physiological state that affects normal human activities. Prolonged fatigue induces a variety of diseases and seriously affects human health, so it is imperative to discover nutritional dietary supplements and treatments without side effects, among which natural anti-fatigue polysaccharides have shown great potential. Polysaccharides, a class of biomolecules produced by a variety of organisms such as plants, animals, bacteria and algae, have attracted much attention in recent years due to their anti-fatigue activity and fewer side effects. This review summarizes the classification, dosage and experimental models of polysaccharides with anti-fatigue activity obtained from different natural sources. We also review the fatigue-relieving effects of these polysaccharides through mechanisms such as modulating oxidative damage, regulating energy metabolism and influencing intestinal flora, as well as the effects of molecular weights, monosaccharide compositions, structural features and chemical modifications of the polysaccharides on their anti-fatigue activities to support their potential application value in functional foods and pharmaceuticals. New valuable insights for future research on natural polysaccharides are also presented in the field of natural production of bio-based functional materials, functional foods and therapeutic agents.

4.
BMC Urol ; 24(1): 140, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972999

RESUMO

OBJECTIVE: The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance. RESULTS: Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890-0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count. CONCLUSION: Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.


Assuntos
Aprendizado de Máquina , Nefrolitotomia Percutânea , Complicações Pós-Operatórias , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Nefrolitotomia Percutânea/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Adulto , Valor Preditivo dos Testes , Idoso , Cálculos Renais/cirurgia
5.
Front Pharmacol ; 15: 1412816, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978983

RESUMO

Background: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

7.
Small ; : e2403859, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030860

RESUMO

The electrocatalytic production of hydrogen peroxide (H2O2) through the two-electron oxygen reduction reaction (2e- ORR) has garnered significant research attention in recent years due to its numerous appealing advantages, such as being eco-friendly and exhibiting high energy conversion efficiency. Metal-free carbon materials with specific catalytic sites have been recognized as potential electrocatalysts for 2e- ORR; however, the design of highly efficient catalysts with well-defined structures and long-term stability for large-scale H2O2 production remains unsatisfactory. In this study, three covalent organic frameworks (COFs) - imine-linked LZU-1, oxazole-linked LZU-190, and thiazole-linked LZU-190(S), are successfully synthesized to explore their catalytic activity in electrocatalytic H2O2 production. Among these, the carbon sites LZU-190(S) are predominantly activated by the introduced adjacent heteroatoms via electronic effects, resulting in much higher H2O2 selectivity compared to the oxazole and imine linkages. This work provides new insights into developing COFs-based electrocatalysts for efficient H2O2 generation.

8.
ACS Appl Mater Interfaces ; 16(24): 30890-30899, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38843539

RESUMO

Multimodal sensing platforms may offer reliable, fast results, but it is still challenging to incorporate biosensors with high discriminating ability in complex biological samples. Herein, we established a highly sensitive dual colorimetric/electrochemical monitoring approach for the detection of hydrogen sulfide (H2S) utilizing Cu-doped In-based metal-organic frameworks (Cu/In-MOFs) combined with a versatile color selector software-based smartphone imaging device. H2S can result in the enhancement of the electrochemical signal because of the electroactive substance copper sulfide (CuxS), the decrease of the colorimetric signal of the characteristic absorption response caused by the strong coordination effect on Cu/In-MOFs, and the obvious changes of red-green-blue (RGB) values of images acquired via an intelligent smartphone. Attractively, the Cu/In-MOFs-based multimodal detection guarantees precise and sensitive detection of H2S with triple-signal detection limits of 0.096 µM (electrochemical signals), 0.098 µM (colorimetric signals), and 0.099 µM (smartphone signals) and an outstanding linear response. This analytical toolkit provides an idea for fabricating a robust, sensitive, tolerant matrix and reliable sensing platform for rapidly monitoring H2S in clinical disease diagnosis and visual supervision.


Assuntos
Colorimetria , Cobre , Técnicas Eletroquímicas , Sulfeto de Hidrogênio , Estruturas Metalorgânicas , Smartphone , Sulfeto de Hidrogênio/análise , Cobre/química , Estruturas Metalorgânicas/química , Colorimetria/métodos , Colorimetria/instrumentação , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Limite de Detecção , Índio/química
9.
Phytomedicine ; 132: 155674, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38901283

RESUMO

BACKGROUND: Cardiovascular and cerebrovascular disease (CCVD) is the leading cause of morbidity and mortality worldwide, imposing a significant economic burden on individuals and societies. For the past few years, Traditional Chinese Medicine (TCM) has attracted much attention due to its advantages such as fewer side effects in the treatment of CCVD. TXL has shown great promise in the treatment of CCVD. PURPOSE: This paper aims to provide a comprehensive introduction to TXL, covering its chemical constituents, quality control, pharmacological properties, adverse reactions, and clinical applications through an extensive search of relevant electronic databases while discussing its current challenges and provides opinions for future study. METHODS: The following electronic databases were searched up to 2023: "TXL", "CCVD", "Chemical constituents", "Quality control" and "Pharmacological properties" were entered as keywords in PubMed, Web of Science, Google Scholar and China National Knowledge Infrastructure Database and WANFANG DATA databases. The PRISMA guidelines were followed in this review process. RESULTS: Studies have confirmed that TXL is effective in treating patients with CCVD and has fewer adverse effects. The aim of this review is to explore TXL anti-CCVD effects in relation to oxidative stress, lipid metabolism and enhanced cardiac function. This review also provides additional information on safety issues. CONCLUSION: TXL plays a key role in the treatment of CCVD by regulating various pathways such as lipid metabolism, oxidative stress and inflammation. However, further clinical trials and animal experiments are needed to provide more evidence and recommendations for its clinical application. This article provides an overview of TXL research to inform and inspire future studies.

10.
BMC Psychiatry ; 24(1): 419, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834943

RESUMO

BACKGROUND: Few studies have simultaneously focused on the associations of vegetable and fruit intake, physical activity, school bullying, and Internet addiction (IA) with depressive symptoms. This study aimed to explore the direct and indirect effects of the above factors on depressive symptoms in adolescents by constructing a structural equation model (SEM). METHODS: This study was conducted in Qingdao from September to November 2021. A total of 6195 secondary school students aged 10-19 years were included in the analysis. Information on all variables was assessed using a self-administered questionnaire. An SEM was constructed with depressive symptoms as the endogenous latent variable, IA as the mediating variable, and vegetable and fruit intake, physical activity, and school bullying as the exogenous latent variables. The standardized path coefficients (ß) were the direct effects between the latent variables, and the indirect effects were obtained by the product of direct effects between relevant latent variables. RESULTS: The median value with the interquartile range of depressive symptom scores was 7 (3,12). Vegetable and fruit intake (ß=-0.100, P<0.001) and physical activity (ß=-0.140, P<0.001) were directly negatively related to depressive symptoms. While school bullying (ß=0.138, P<0.001) and IA (ß=0.452, P<0.001) were directly positively related to depressive symptoms. IA had the greatest impact on depressive symptoms. Vegetable and fruit intake, physical activity, and school bullying could not only directly affect depressive symptoms, but also indirectly affect depressive symptoms through the mediating effect of IA, the indirect effects and 95% confidence intervals (CIs) were -0.028 (-0.051, -0.007), -0.114 (-0.148, -0.089) and 0.095 (0.060, 0.157), respectively. The results of the multi-group analysis showed that the SEM we constructed still fit in boy and girl groups. CONCLUSIONS: The results indicated that vegetable and fruit intake, physical activity, school bullying, and IA had a significant direct impact on depressive symptoms, among which IA had the greatest impact. In addition, both vegetable and fruit intake, school bullying, and physical activity indirectly affected depressive symptoms through the mediating effect of IA. The impact of IA on depressive symptoms should be given extra attention by schools and parents. This study provides a scientific and effective basis for the prevention and control of adolescent depressive symptoms.


Assuntos
Bullying , Depressão , Exercício Físico , Frutas , Transtorno de Adição à Internet , Estudantes , Verduras , Humanos , Adolescente , Masculino , Bullying/psicologia , Bullying/estatística & dados numéricos , Feminino , Depressão/psicologia , Depressão/epidemiologia , Exercício Físico/psicologia , Criança , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Transtorno de Adição à Internet/psicologia , Transtorno de Adição à Internet/epidemiologia , Instituições Acadêmicas , Adulto Jovem , China/epidemiologia
11.
J Inflamm Res ; 17: 3527-3549, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836243

RESUMO

Ulcerative colitis (UC) is a chronic non-sp ecific inflammatory disease of the colorectal mucosa. Researchers have associated UC onset with familial genetics, lifestyle behavior, inflammatory immune factors, intestinal microbiota, and the integrity of the intestinal mucosal barrier. The primary therapeutic interventions for UC consist of pharmacological management to control inflammation and promote mucosal healing and surgical interventions. The available drugs effectively control and decelerate the progression of UC in most patients; nonetheless, their long-term administration can exert adverse effects and influence the therapeutic effect. Plant essential oils (EOs) refer to a group of hydrophobic aromatic volatile substances. EOs have garnered considerable attention in both domestic and international research because of their anti-inflammatory, antibacterial, and antioxidant properties. They include peppermint, peppercorns, rosemary, and lavender, among others. Researchers have investigated the role of EOs in medicine and have elucidated their potential to mitigate the detrimental effects of UC through their anti-inflammatory, antioxidant, antidepressant, and anti-insomnia properties as well as their ability to regulate the intestinal flora. Furthermore, EOs exert minimal toxic adverse effects, further enhancing their appeal for therapeutic applications. However, these speculations are based on theoretical experiments, thereby warranting more clinical studies to confirm their effectiveness and safety. In this article, we aim to provide an overview of the advancements in utilizing natural medicine EOs for UC prevention and treatment. We will explore the potential pathogenesis of UC and examine the role of EOs therapy in basic research, quality stability, and management specification of inadequate EOs for UC treatment. We intend to offer novel insights into the use of EOs in UC prevention and management.

12.
Int J Hyperthermia ; 41(1): 2369305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38897626

RESUMO

PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.


Assuntos
Intestino Delgado , Animais , Suínos , Gases
13.
Healthcare (Basel) ; 12(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38891188

RESUMO

Online medical teams (OMTs), a new mode of online healthcare service, have emerged in online health communities (OHCs) in China. This study attempts to explore the underlying mechanism of how OMTs' engagement influences patient satisfaction through the lens of semantic features. This study also scrutinizes the moderating effect of multiple specializations on the link between OMTs' engagement and semantic features. We utilized a linear model that had fixed effects controlled at the team level for analysis. A bootstrapping approach using 5000 samples was employed to test the mediation effects. The findings reveal that OMTs' engagement significantly improves language concreteness in online team consultations, which subsequently enhances patient satisfaction. OMT engagement has a negative impact on emotional intensity, ultimately decreasing patient satisfaction. Multiple specializations strengthen the impact of OMT engagement on both language concreteness and emotional intensity. This study contributes to the literature on OMTs and patient satisfaction, providing insights into patients' perceptions of OMTs' engagement during online team consultation. This study also generates several implications for the practice of OHCs and OMTs.

14.
Redox Biol ; 75: 103253, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38936254

RESUMO

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gαi/q and their ability to bind GDP-bound (inactive form) Gαi/q. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gαi/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gαi/q signaling from the plasma membrane. This is achieved by recruiting Gαi/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gαi/q signaling, thereby uncovering a novel mechanism for terminating Gαi/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gαi/q signaling beyond the plasma membrane.

15.
BMC Plant Biol ; 24(1): 615, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937722

RESUMO

Amorphophallus is a perennial monocotyledonous herbaceous plant native to the southwestern region of China, widely used in various fields such as food processing, biomedicine and chemical agriculture. However, Amorphophallus is a typical thermolabile plant, and the continuous high temperature in summer have seriously affected the growth, development and economic yield of Amorphophallus in recent years. Calmodulin (CaM), a Ca2+ sensor ubiquitous in eukaryotes, is the most important multifunctional receptor protein in plant cells, which affects plant stress resistance by participating in the activities of a variety of signaling molecules. In this study, the key gene AaCaM3 for the Ca2+-CaM regulatory pathway was obtained from A. albus, the sequence analysis confirmed that it is a typical calmodulin. The qRT-PCR results demonstrated that with the passage of heat treatment time, the expression of AaCaM3 was significantly upregulated in A. albus leaves. Subcellular localization analysis revealed that AaCaM3 localized on the cytoplasm and nucleus. Meanwhile, heterologous transformation experiments have shown that AaCaM3 can significantly improve the heat tolerance of Arabidopsis under heat stress. The promoter region of AaCaM3 was sequenced 1,338 bp by FPNI-PCR and GUS staining assay showed that the promoter of AaCaM3 was a high-temperature inducible promoter. Yeast one-hybrid analysis and Luciferase activity reporting system analysis showed that the AaCaM3 promoter may interact with AaHSFA1, AaHSFA2c, AaHSP70, AaDREB2a and AaDREB2b. In conclusion, this study provides new ideas for further improving the signal transduction network of high-temperature stress in Amorphophallus.


Assuntos
Arabidopsis , Calmodulina , Proteínas de Plantas , Calmodulina/metabolismo , Calmodulina/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Resposta ao Choque Térmico/genética , Temperatura Alta , Fabaceae/genética , Fabaceae/fisiologia , Fabaceae/metabolismo , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética , Regiões Promotoras Genéticas
16.
Cell Biosci ; 14(1): 81, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886783

RESUMO

BACKGROUND: Histone ubiquitination modification is emerging as a critical epigenetic mechanism involved in a range of biological processes. In vitro reconstitution of ubiquitinated nucleosomes is pivotal for elucidating the influence of histone ubiquitination on chromatin dynamics. RESULTS: In this study, we introduce a Non-Denatured Histone Octamer Ubiquitylation (NDHOU) approach for generating ubiquitin or ubiquitin-like modified histone octamers. The method entails the co-expression and purification of histone octamers, followed by their chemical cross-linking to ubiquitin using 1,3-dibromoacetone. We demonstrate that nucleosomes reconstituted with these octamers display a high degree of homogeneity, rendering them highly compatible with in vitro biochemical assays. These ubiquitinated nucleosomes mimic physiological substrates in function and structure. Additionally, we have extended this method to cross-linking various histone octamers and three types of ubiquitin-like proteins. CONCLUSIONS: Overall, our findings offer an efficient strategy for producing ubiquitinated nucleosomes, advancing biochemical and biophysical studies in the field of chromatin biology.

17.
Acta Biomater ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871203

RESUMO

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. STATEMENT OF SIGNIFICANCE: Cutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.

18.
J Ethnopharmacol ; 332: 118403, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38821137

RESUMO

ETHNOPHARMACOLOGIC RELEVANCE: Valeriana jatamansi Jones, belongs to the Valerianaceae family, is widely used in traditional Chinese medicine (TCM) and Ayurveda, traditional Indian medicine (TIM). This traditional herb has been officially listed in the pharmacopoeia of sixteen countries. Its usage was first described in Diannan Bencao, also known as "Zhizhuxiang", is a famous folk medicine herb with a long history of medicinal usage in China, and it was used to treat indigestion, flu, and mental disorders in the Han, Achang, Bai, Blang, Dai, Jingpo, Naxi, and Wa ethnic groups. In recent years, V. jatamansi has attracted worldwide attention as an important medicinal due to its pharmacological activity especially in nervous and digestive systems, and multiple uses. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, and quality control of V. jatamansi. MATERIALS AND METHODS: The relevant information of V. jatamansi was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D. and MSc dissertations, using "Valeriana jatamansi Jones", "Valeriana jatamansi", and "" as keywords. After eliminating repetitive and low-quality reports, the remaining reports were analyzed and summarized to prepare this review. Plant information was retrieved by www.worldfloraonline.org and www.gbif.org using "Valeriana jatamansi Jones" as keyword. RESULTS: V. jatamansi has been historically utilized as a traditional medicine to treat various diseases, including infectious, inflammatory, neurological, and gastrointestinal disorders. More than 400 compounds have been identified in V. jatamansi including iridoids, volatile oils, lignans, flavonoids, phenolic acids, phenylpropanoids, sesquiterpenes, sesquiterpene hydrocarbons, triterpenes as well as other compounds. The plant extracts and compounds showed various pharmacological activities such as antitumor, cytotoxic, antivirus, etc. In addition, V. jatamansi has found various applications in the agricultural, food, and cosmetics industry. CONCLUSION: A review of literature shows V. jatamansi has pharmacological properties valuable in treating diseases, particularly for antianxiety and gastrointestinal disorders. Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and in vivo, with a lack of pharmacokinetics, clinical trials and underlying mechanisms. Consequently, it becomes important to embark on additional researchs to elucidate the pharmacokinetics, material basis and mechanisms of V. jatamansi, thereby realizing the aspiration of its comprehensive utilization and sustainable development.


Assuntos
Etnofarmacologia , Compostos Fitoquímicos , Controle de Qualidade , Valeriana , Valeriana/química , Humanos , Animais , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Fitoterapia , Medicina Tradicional
19.
Cell ; 187(12): 3024-3038.e14, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38781969

RESUMO

Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.


Assuntos
Proteínas de Plantas , Regeneração , Transdução de Sinais , Solanum lycopersicum , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/metabolismo , Regulação da Expressão Gênica de Plantas , Peptídeos/metabolismo
20.
Sci Data ; 11(1): 546, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806531

RESUMO

For highly autonomous vehicles, human does not need to operate continuously vehicles. The brain-computer interface system in autonomous vehicles will highly depend on the brain states of passengers rather than those of human drivers. It is a meaningful and vital choice to translate the mental activities of human beings, essentially playing the role of advanced sensors, into safe driving. Quantifying the driving risk cognition of passengers is a basic step toward this end. This study reports the creation of an fNIRS dataset focusing on the prefrontal cortex activity in fourteen types of highly automated driving scenarios. This dataset considers age, sex and driving experience factors and contains the data collected from an 8-channel fNIRS device and the data of driving scenarios. The dataset provides data support for distinguishing the driving risk in highly automated driving scenarios via brain-computer interface systems, and it also provides the possibility of preventing potential hazards in some scenarios, in which risk remains at a high value for an extended period, before hazard occurs.


Assuntos
Condução de Veículo , Cognição , Adulto , Feminino , Humanos , Masculino , Automação , Interfaces Cérebro-Computador , Córtex Pré-Frontal/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho
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