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1.
J Drug Target ; : 1-13, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958251

RESUMO

Exosome therapy has garnered significant attention due to its natural delivery capabilities, low toxicity, high biocompatibility, and potential for personalised treatment through engineering modifications. Recent studies have highlighted the ability of tumour cell-derived exosomes (TDEs) to interact with immune cells or modify the immune microenvironment to suppress host immune responses, as well as their unique homing ability to parental cells. The core question of this study is whether this immunomodulatory property of TDEs can be utilised for the immunotherapy of inflammatory diseases. In our experiments, we prepared exosomes derived from murine colon cancer cells CT26 (CT26 exo) using ultracentrifugation, characterised them, and conducted proteomic analysis. The therapeutic potential of CT26 exo was evaluated in our dextran sulphate sodium salt (DSS)-induced inflammatory bowel disease (IBD) mouse model. Compared to the control and 293 T exo treatment groups, mice treated with CT26 exo showed a reduction in the disease activity index (DAI) and colon shortening rate, with no noticeable weight loss. Haematoxylin and eosin (H&E) staining of colon paraffin sections revealed reduced inflammatory infiltration and increased epithelial goblet cells in the colons of CT26 exo-treated group. Furthermore, we conducted preliminary mechanistic explorations by examining the phenotyping and function of CD4+ T cells and dendritic cells (DCs) in the colonic lamina propria of mice. The results indicated that the ameliorative effect of CT26 exosomes might be due to their inhibition of pro-inflammatory cytokine secretion by colonic DCs and selective suppression of Th17 cell differentiation in the colon. Additionally, CT26 exo exhibited good biosafety. Our findings propose a novel exosome-based therapeutic approach for IBD and suggest the potential application of TDEs in the treatment of inflammatory diseases.

2.
PLoS One ; 19(6): e0302371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38857223

RESUMO

Formica is a large genus in the family Formicidae with high diversity in its distribution, morphology, and physiology. To better understand evolutionary characteristics of Formica, the complete mitochondrial genomes (mitogenomes) of two Formica species were determined and a comparative mitogenomic analysis for this genus was performed. The two newly sequenced Formica mitogenomes each included 37 typical mitochondrial genes and a large non-coding region (putative control region), as observed in other Formica mitogenomes. Base composition, gene order, codon usage, and tRNA secondary structure were well conserved among Formica species, whereas diversity in sequence size and structural characteristics was observed in control regions. We also observed several conserved motifs in the intergenic spacer regions. These conserved genomic features may be related to mitochondrial function and their highly conserved physiological constraints, while the diversity of the control regions may be associated with adaptive evolution among heterogenous habitats. A negative AT-skew value on the majority chain was presented in each of Formica mitogenomes, indicating a reversal of strand asymmetry in base composition. Strong codon usage bias was observed in Formica mitogenomes, which was predominantly determined by nucleotide composition. All 13 mitochondrial protein-coding genes of Formica species exhibited molecular signatures of purifying selection, as indicated by the ratio of non-synonymous substitutions to synonymous substitutions being less than 1 for each protein-coding gene. Phylogenetic analyses based on mitogenomic data obtained fairly consistent phylogenetic relationships, except for two Formica species that had unstable phylogenetic positions, indicating mitogenomic data are useful for constructing phylogenies of ants. Beyond characterizing two additional Formica mitogenomes, this study also provided some key evolutionary insights into Formica.


Assuntos
Formigas , Evolução Molecular , Genoma Mitocondrial , Filogenia , Animais , Formigas/genética , Uso do Códon , RNA de Transferência/genética , Composição de Bases
3.
Polymers (Basel) ; 16(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38794621

RESUMO

Bacterial infection is a common complication in bone defect surgery, in which infection by clinically resistant bacteria has been a challenge for the medical community. Given this emerging problem, the discovery of novel natural-type inhibitors of drug-resistant bacteria has become imperative. Brucine, present in the traditional Chinese herb Strychnine semen, is reported to exert analgesic and anti-inflammatory effects. Brucine's clinical application was limited because of its water solubility. We extracted high-purity BS by employing reflux extraction and crystallization, greatly improved its solubility, and evaluated its antimicrobial activity against E. coli and S. aureus. Importantly, we found that BS inhibited the drug-resistant strains significantly better than standard strains and achieved sterilization by disrupting the bacterial cell wall. Considering the safety concerns associated with the narrow therapeutic window of BS, a 3D BS-PLLA/PGA bone scaffold system was constructed with SLS technology and tested for its performance, bacteriostatic behaviors, and biocompatibility. The results have shown that the drug-loaded bone scaffolds had not only long-term, slow-controlled release with good cytocompatibility but also demonstrated significant antimicrobial activity in antimicrobial testing. The above results indicated that BS may be a potential drug candidate for the treatment of antibiotic-resistant bacterial infections and that scaffolds with enhanced antibacterial activity and mechanical properties may have potential applications in bone tissue engineering.

4.
Dalton Trans ; 53(20): 8750-8755, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712563

RESUMO

Direct ethanol fuel cells (DEFCs), which have been widely recognized as nontoxic and green energy conversion devices, show attractive application prospects for liquid hydrogen-carriers, due to the higher specific energy and lower toxicity of ethanol. Pt-based catalysts are widely used in DEFCs, while their poor poisoning resistance highlights the importance of composition and structure optimization. Herein, we synthesized a series of reduced graphene oxide supported ternary alloy AuxPt1-xCu3/rGO (x = 0-1) catalysts with excellent ethanol oxidation performance and a composition-dependent volcano plot trend of the ordering degree was observed and rationalized. The highest Pt-normalized mass activity of Au0.8Pt0.2Cu3/rGO is attributed to the optimized CO binding energy according to DFT calculations. This work not only provides an efficient EOR catalyst based on ordered alloys AuxPt1-xCu3 (x = 0-1), but also offers valuable insight into the role of a third metal in tuning the structure and function of alloys.

5.
Sci Rep ; 14(1): 12573, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822129

RESUMO

Through tests and micro-observations, the static and dynamic mechanical properties and microstructure of rubber concrete samples modified with varying amounts of silica fume and polypropylene fiber content were explored. The results indicate that incorporation of silica fume and polypropylene fiber can effectively enhance the performance of rubber concrete. Moreover, at 10% and 0.1% of silica fume and polypropylene fiber content respectively, rubber concrete's compressive strength, splitting tensile strength, flexural strength, and dynamic compressive strength reached maxima. Furthermore, microstructure characteristic analysis indicated that inadequate adhesion between rubber particles and the matrix is responsible for compromised bearing capacity in unmodified rubber concrete. However, with the addition of silica fume and polypropylene fiber, the fiber binds the rubber particles closely with the matrix, while the silica fume fills the gaps between the matrix components. This combination results in rubber concrete with a denser internal structure and enhances its bearing capacity significantly.

6.
Transl Lung Cancer Res ; 13(4): 901-929, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38736488

RESUMO

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

7.
Plant Cell Physiol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619117

RESUMO

Verticillium dahliae is a kind of pathogenic fungus that brings about wilt disease and great losses in cotton. The molecular mechanism of the effectors in V. dahliae regulating cotton immunity remains largely unknown. Here we identified an effector of V. dahliae, VdPHB1, whose gene expression is highly induced by infection. VdPHB1 protein is localized in the intercellular space of cotton plants. Knockout VdPHB1 gene in V. dahliae had no effect on pathogen growth, but decreased the virulence in cotton. VdPHB1 ectopically expressed Arabidopsis plants were growth-inhibited and significantly susceptible to V. dahliae. Further, VdPHB1 interacted with the type II metacaspase GhMC4. GhMC4 gene silenced cotton plants were more sensitive to V. dahliae with reduced expressions of pathogen defense-related and programmed cell death genes. The accumulation of GhMC4 protein were concurrently repressed when VdPHB1 protein expressed during infection. In summary, these results revealed a novel molecular mechanism of virulence regulation that the secreted effector VdPHB1 represses the activity of cysteine protease for helping V. dahliae infection in cotton.

8.
BMC Pulm Med ; 24(1): 203, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658883

RESUMO

BACKGROUND: Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. METHODS: A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500-750 µm microspheres, and group B patients were treated with 700-900 µm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. RESULTS: Median follow-up was 30.2 months (range, 20.3-56.5 months). The final analysis included a total of 112 patients (49-77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500-750 µm Embosphere microspheres, and group B (N = 44), which received 700-900 µm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12-2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10-2.72; P = 0.028) were independent risk factors for recurrent bleeding. CONCLUSIONS: For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500-750 µm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700-900 µm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700-900 µm) Embosphere microspheres is associated with the reduced cost of an embolic agent.


Assuntos
Resinas Acrílicas , Artérias Brônquicas , Bronquiectasia , Embolização Terapêutica , Hemoptise , Microesferas , Humanos , Hemoptise/terapia , Hemoptise/etiologia , Estudos Retrospectivos , Masculino , Feminino , Embolização Terapêutica/métodos , Pessoa de Meia-Idade , Idoso , Bronquiectasia/complicações , Bronquiectasia/terapia , Gelatina/administração & dosagem , Gelatina/uso terapêutico , Resultado do Tratamento , Tamanho da Partícula
9.
Cell Metab ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38569557

RESUMO

Activating Nrf2 by small molecules is a promising strategy to treat postmenopausal osteoporosis. However, there is currently no Nrf2 activator approved for treating chronic diseases, and the downstream mechanism underlying the regulation of Nrf2 on osteoclast differentiation remains unclear. Here, we found that bitopertin, a clinical-stage glycine uptake inhibitor, suppresses osteoclast differentiation and ameliorates ovariectomy-induced bone loss by activating Nrf2. Mechanistically, bitopertin interacts with the Keap1 Kelch domain and decreases Keap1-Nrf2 binding, leading to reduced Nrf2 ubiquitination and degradation. Bitopertin is associated with less adverse events than clinically approved Nrf2 activators in both mice and human subjects. Furthermore, Nrf2 transcriptionally activates ferroportin-coding gene Slc40a1 to reduce intracellular iron levels in osteoclasts. Loss of Nrf2 or iron supplementation upregulates ornithine-metabolizing enzyme Odc1, which decreases ornithine levels and thereby promotes osteoclast differentiation. Collectively, our findings identify a novel clinical-stage Nrf2 activator and propose a novel Nrf2-iron-ornithine metabolic axis in osteoclasts.

10.
Curr Opin Genet Dev ; 86: 102195, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643591

RESUMO

Adenosine-to-inosine RNA editing, catalyzed by the enzymes ADAR1 and ADAR2, stands as a pervasive RNA modification. A primary function of ADAR1-mediated RNA editing lies in labeling endogenous double-stranded RNAs (dsRNAs) as 'self', thereby averting their potential to activate innate immune responses. Recent findings have highlighted additional roles of ADAR1, independent of RNA editing, that are crucial for immune control. Here, we focus on recent progress in understanding ADAR1's RNA editing-dependent and -independent roles in immune control. We describe how ADAR1 regulates various dsRNA innate immune receptors through distinct mechanisms. Furthermore, we discuss the implications of ADAR1 and RNA editing in diseases, including autoimmune diseases and cancers.


Assuntos
Adenosina Desaminase , Imunidade Inata , Edição de RNA , Proteínas de Ligação a RNA , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Imunidade Inata/genética , RNA de Cadeia Dupla/genética , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia
11.
Molecules ; 29(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38675536

RESUMO

Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.


Assuntos
Constipação Intestinal , Morus , Folhas de Planta , Sesamum , Morus/química , Constipação Intestinal/tratamento farmacológico , Folhas de Planta/química , Sesamum/química , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolômica/métodos , Masculino , Motilidade Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Multiômica
12.
Front Immunol ; 15: 1344681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469310

RESUMO

Exosomes are small extracellular vesicles (sEVs) secreted by cells. With advances in the study of sEVs, they have shown great potential in the diagnosis and treatment of disease. However, sEV therapy usually requires a certain dose and purity of sEVs to achieve the therapeutic effect, but the existing sEV purification technology exists in the form of low yield, low purity, time-consuming, complex operation and many other problems, which greatly limits the application of sEVs. Therefore, how to obtain high-purity and high-quality sEVs quickly and efficiently, and make them realize large-scale production is a major problem in current sEV research. This paper discusses how to improve the purity and yield of sEVs from the whole production process of sEVs, including the upstream cell line selection and cell culture process, to the downstream isolation and purification, quality testing and the final storage technology.


Assuntos
Exossomos , Vesículas Extracelulares , Transporte Biológico , Técnicas de Cultura de Células , Linhagem Celular
13.
Biomacromolecules ; 25(4): 2438-2448, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38502912

RESUMO

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.


Assuntos
Quitosana , Hidrogéis , Hidrogéis/farmacologia , Cicatrização , Antibacterianos/farmacologia , Ciprofloxacina , Bandagens
14.
Environ Int ; 186: 108594, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38527398

RESUMO

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life-like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.


Assuntos
Antibacterianos , Cobre , Microbioma Gastrointestinal , Tetraciclina , Animais , Cobre/toxicidade , Tetraciclina/farmacologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Bactérias/efeitos dos fármacos , Bactérias/genética , Fezes/microbiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-38508351

RESUMO

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.


Assuntos
Hericium , Peróxido de Hidrogênio , Estresse Oxidativo , Animais , Suínos , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Linhagem Celular , Células Epiteliais , Apoptose
16.
Environ Pollut ; 347: 123674, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38458517

RESUMO

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Ratos , Animais , Remodelação das Vias Aéreas , Fenótipo Secretor Associado à Senescência , Miócitos de Músculo Liso , Asma/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Colágeno Tipo I , Proliferação de Células , Material Particulado/metabolismo , Células Cultivadas
17.
Proc Natl Acad Sci U S A ; 121(6): e2316775121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38300874

RESUMO

High pressure has triggered various novel states/properties in condensed matter, as the most representative and dramatic example being near-room-temperature superconductivity in highly pressured hydrides (~200 GPa). However, the mechanism of superconductivity is not confirmed, due to the lacking of effective approach to probe the electronic band structure under such high pressures. Here, we theoretically propose that the band structure and electron-phonon coupling (EPC) of high-pressure quantum states can be probed by solid-state high harmonic generation (sHHG). This strategy is investigated in high-pressure Im-3m H3S by the state-of-the-art first-principles time-dependent density-functional theory simulations, where the sHHG is revealed to be strongly dependent on the electronic structures and EPC. The dispersion of multiple bands near the Fermi level is effectively retrieved along different momentum directions. Our study provides unique insights into the potential all-optical route for band structure and EPC probing of high-pressure quantum states, which is expected to be helpful for the experimental exploration of high-pressure superconductivity in the future.

18.
Asian J Psychiatr ; 93: 103913, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219553

RESUMO

Suicide attempts can cause serious physical harm or death. It would be crucial to gain a better understanding of the comparative efficacy of non-pharmacological interventions. We aimed to identify which non-pharmacological interventions are more effective in preventing suicide attempts. PubMed, Web of Science, and EMBASE databases were searched systematically from their inception until 3 April 2023. To be eligible for inclusion, randomized controlled trials (RCTs) had to meet the following criteria: Participants were individuals who had suicidal ideation or a history of severe self-harm or attempted suicide. A network meta-analysis was performed using a random effects model to estimate the treatment effect of various non-pharmacological interventions. (PROSPERO registration number: CRD42023411393). We obtained data from 54 studies involving 17,630 participants. Our primary analysis found that Cognitive therapy (CT) (OR=0.19, 95%CI =0.04-0.81), Dialectical Behavior Therapy (DBT) (OR=0.37, 95%CI =0.13-0.97), Cognitive-behavioral therapy (CBT) (OR=0.42, 95%CI =0.17-0.99), and Brief intervention and contact (BIC) (OR=0.65, 95%CI=0.44-0.94) were superior to TAU (within the longest available follow-up time) in preventing suicide attempts, while other intervention methods do not show significant advantages over TAU. Secondary analysis showed that the two intervention measures (CT and BIC) were effective when follow-up time did not exceed 6 months, but there was no effective intervention measure with longer follow-up times. CT, DBT, CBT, and BIC have a better effect in preventing suicide attempts than other non-pharmacological interventions. Additional research is necessary to validate which interventions, as well as which combinations of interventions, are the most effective.


Assuntos
Terapia Cognitivo-Comportamental , Comportamento Autodestrutivo , Humanos , Tentativa de Suicídio/psicologia , Metanálise em Rede , Terapia Cognitivo-Comportamental/métodos , Ideação Suicida , Comportamento Autodestrutivo/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
J Drug Target ; 32(2): 213-222, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38164940

RESUMO

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. In vivo experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.


Assuntos
Toxinas Botulínicas Tipo A , Botulismo , Clostridium botulinum , Humanos , Toxinas Botulínicas Tipo A/metabolismo , Toxinas Botulínicas Tipo A/uso terapêutico , Botulismo/tratamento farmacológico , Botulismo/prevenção & controle , Clostridium botulinum/metabolismo , Anticorpos Monoclonais , Antivirais/uso terapêutico
20.
Prostaglandins Other Lipid Mediat ; 170: 106803, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040190

RESUMO

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.


Assuntos
Antiasmáticos , Asma , Lipoxinas , Camundongos , Animais , Lipoxinas/farmacologia , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Antiasmáticos/efeitos adversos , Pulmão/metabolismo , Citocinas/metabolismo , Extratos Vegetais/farmacologia , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
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