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1.
Biochem Biophys Res Commun ; 693: 149374, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38096616

RESUMO

Cervical cancer, a common malignancy in women, poses a significant health burden worldwide. In this study, we aimed to investigate the expression, function, and potential mechanisms of NADH: ubiquinone oxidoreductase subunit A8 (NDUFA8) in cervical cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) database and immunohistochemical scoring were used to analyze NDUFA8 expression in cervical cancer tissues and normal tissues. Quantitative real-time PCR and Western blot analyses were performed to assess the expression level of NDUFA8 in cervical cancer cell lines. NDUFA8 knockdown or overexpression experiments were conducted to evaluate its impact on cell proliferation and apoptosis. The mitochondrial respiratory status was analyzed by measuring cellular oxygen consumption, adenosine triphosphate (ATP) levels, and the expression levels of Mitochondrial Complex I activity, and Mitochondrial Complex IV-associated proteins Cytochrome C Oxidase Subunit 5B (COX5B) and COX6C. NDUFA8 exhibited high expression levels in cervical cancer tissues, and these levels were correlated with reduced survival rates. A significant upregulation of NDUFA8 expression was observed in cervical cancer cell lines compared to normal cells. Silencing NDUFA8 hindered cell proliferation, promoted apoptosis, and concurrently suppressed cellular mitochondrial respiration, resulting in decreased levels of available ATP. Conversely, NDUFA8 overexpression induced the opposite effects. Herein, we also found that E1A Binding Protein P300 (EP300) overexpression facilitated Histone H3 Lysine 27 (H3K27) acetylation enrichment, enhancing the activity of the NDUFA8 promoter region. NDUFA8, which is highly expressed in cervical cancer, is regulated by transcriptional control via EP300/H3K27 acetylation. By promoting mitochondrial respiration, NDUFA8 contributes to cervical cancer cell proliferation and apoptosis. These findings provide novel insights into NDUFA8 as a therapeutic target in cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Fatores de Transcrição/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Apoptose/genética , Proliferação de Células/genética , Respiração , Trifosfato de Adenosina , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Proteína p300 Associada a E1A/genética , Proteína p300 Associada a E1A/metabolismo
2.
Small ; 20(27): e2306616, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342672

RESUMO

Metal-organic frameworks (MOFs) are crystalline porous materials with a long-range ordered structure and excellent specific surface area and have found a wide range of applications in diverse fields, such as catalysis, energy storage, sensing, and biomedicine. However, their poor electrical conductivity and chemical stability, low capacity, and weak adhesion to substrates have greatly limited their performance. Doping has emerged as a unique strategy to mitigate the issues. In this review, the concept, classification, and characterization methods of doped MOFs are first introduced, and recent progress in the synthesis and applications of doped MOFs, as well as the rapid advancements and applications of first-principles calculations based on the density functional theory (DFT) in unraveling the mechanistic origin of the enhanced performance are summarized. Finally, a perspective is included to highlight the key challenges in doping MOF materials and an outlook is provided on future research directions.

3.
Environ Sci Technol ; 58(36): 15938-15948, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39192575

RESUMO

Accurately mapping ground-level ozone concentrations at high spatiotemporal resolution (daily, 1 km) is essential for evaluating human exposure and conducting public health assessments. This requires identifying and understanding a proxy that is well-correlated with ground-level ozone variation and available with spatiotemporal high-resolution data. This study introduces a high-resolution ozone modeling method utilizing the XGBoost algorithm with satellite-derived land surface temperature (LST) as the primary predictor. Focusing on China in 2019, our model achieved a cross-validation R2 of 0.91 and a root-mean-square error (RMSE) of 13.51 µg/m3. We provide detailed maps highlighting ground-level ozone concentrations in urban areas, uncovering spatial variations previously unresolved, along with time series aligning with established understandings of ozone dynamics. Our local interpretation of the machine learning model underscores the significant contribution of LST to spatiotemporal ozone variations, surpassing other meteorological, pollutant, and geographical predictors in its influence. Validation results indicate that model performance decreases as spatial resolution becomes coarser, with R2 decreasing from 0.91 for the 1 km model to 0.85 for the 25 km model. The methodology and data sets generated by this study offer new insights into ground-level ozone variability and mapping and can significantly aid in exposure assessment and epidemiological research related to this critical environmental challenge.


Assuntos
Aprendizado de Máquina , Ozônio , Temperatura , Ozônio/análise , Monitoramento Ambiental/métodos , China , Poluentes Atmosféricos , Humanos
4.
Bioorg Chem ; 145: 107218, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38377820

RESUMO

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.


Assuntos
Carbocianinas , Corantes Fluorescentes , Melanoma , Humanos , Corantes Fluorescentes/farmacologia , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Dinâmica Mitocondrial , Apoptose
5.
Phytochem Anal ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258551

RESUMO

INTRODUCTION: Amomum fruit, also known as Sharen, serves as both a functional food and a traditional Chinese medicine with significant pharmacological activities. However, there are three botanical origins of Amomum fruit: Amomum villosum Lour. (AVL), Amomum villosum Lour. var. xanthioides T. L. (AVX), and Amomum longiligulare T. L. Wu (ALW). OBJECTIVE: Conducting a comprehensive chemical composition analysis of Amomum fruit from three botanical origins aims to identify potential differences in metabolic characteristics. METHODS: To annotate the metabolic characteristic ions of multi-origin Amomum fruit, we employed metabolomic techniques, including ultra-high-performance liquid chromatography (LC) coupled with linear ion trap-Orbitrap-tandem mass spectrometry (MS) and gas chromatography-MS, in conjunction with feature-based molecular networking technology. Additionally, chemometrics was utilized to examine the correlations between the various botanical origins. RESULTS: A total of 201 non-volatile and 151 volatile metabolites were annotated, and most of the proanthocyanidins and flavonoids were identified by feature-based molecular networking. Additionally, 61 non-volatile and 45 volatile feature ions were screened out for classification. Principal component analysis, orthogonal projection to latent structures discrimination analysis, and heat map analysis were employed to clearly distinguish the metabolite profiles of Amomum fruit from different origins. Hierarchical clustering analysis indicated that proanthocyanidins C1 and C2, as well as proanthocyanins oligomers, show significant differential expression between AVX and AVL, which could be the new quality markers for the classification. CONCLUSION: Classification of the botanical origin of Amomum fruit based on LC-MS characteristic ions proved to be more advantageous. This study introduces new strategies and technical support for the quality control of Amomum fruit and facilitates the identification of unknown compounds for future research.

6.
Environ Geochem Health ; 46(9): 328, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012544

RESUMO

Alpine ecosystems are important terrestrial carbon (C) pools, and microbial decomposers play a key role in litter decomposition. Microbial metabolic limitations in these ecosystems, however, remain unclear. The objectives of this study aim to elucidate the characteristics of microbial nutrient limitation and their C use efficiency (CUE), and to evaluate their response to environmental factors. Five ecological indicators were utilized to assess and compare the degree of microbial elemental homeostasis and the nutrient limitations of the microbial communities among varying stages of litter decomposition (L, F, and H horizon) along an altitudinal gradient (2800, 3000, 3250, and 3500 m) under uniform vegetation (Abies fabri) on Gongga Mountain, eastern Tibetan Plateau. In this study, microorganisms in the litter reached a strictly homeostatic of C content exclusively during the middle stage of litter decomposition (F horizon). Based on the stoichiometry of soil enzymes, we observed that microbial N- and P-limitation increased during litter degradation, but that P-limitation was stronger than N-limitation at the late stages of degradation (H horizon). Furthermore, an increase in microbial CUE corresponded with a reduction in microbial C-limitation. Additionally, redundancy analysis (RDA) based on forward selection further showed that microbial biomass C (MBC) is closely associated with the enzyme activities and their ratios, and MBC was also an important factor in characterizing changes in microbial nutrient limitation and CUE. Our findings suggest that variations in MBC, rather than N- and P-related components, predominantly influence microbial metabolic processes during litter decomposition on Gongga Mountain, eastern Tibetan Plateau.


Assuntos
Carbono , Microbiologia do Solo , Carbono/metabolismo , Nitrogênio/metabolismo , Tibet , Fósforo/metabolismo , Nutrientes/metabolismo , Folhas de Planta/metabolismo , Solo/química , Biomassa , Ecossistema , Bactérias/metabolismo
7.
Biochem Biophys Res Commun ; 679: 129-138, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37690423

RESUMO

Although the prognosis for papillary thyroid carcinoma (PTC) is generally good, a certain proportion of patients show recurrent or advanced disease, indicating the need for further development of targeted medications. The purpose of this study was to explore the interventional effects of colchicine on PTC and the potential mechanisms or targets. We obtained PTC-related targets from the database and colchicine targets by predicting them. We screened the common targets of colchicine and the PTC-related target histone deacetylase 1 (HDAC1) and verified through molecular docking that colchicine has a good affinity for HDAC1, i.e., colchicine may act on PTC by affecting HDAC1. We then used CCK-8, colony formation, mitochondrial membrane potential and apoptosis assays to confirm that colchicine could inhibit the proliferation and promote the apoptosis of PTC cells and verified by RT‒qPCR, Western blot, and cellular immunofluorescence assays that colchicine could inhibit the expression of HDAC1 in PTC cells. The cytotoxicity and inhibitory effect of colchicine on HDAC1 in PTC cells was stronger than that in normal thyroid cells. We then applied an HDAC1 inhibitor, pyroxamide, to verify that inhibition of HDAC1 inhibits proliferation and promotes apoptosis in PTC cells. Therefore, we conclude that colchicine can inhibit the proliferation and promote the apoptosis of PTC cells likely due to its inhibitory effect on HDAC1. This finding implies that colchicine may be helpful for therapeutic intervention in PTC and that HDAC1 may be a promising clinical therapeutic target.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/genética , Histona Desacetilase 1/metabolismo , Colchicina/farmacologia , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Proliferação de Células , Apoptose/fisiologia , Regulação Neoplásica da Expressão Gênica , Movimento Celular
8.
Small ; 19(8): e2204121, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36526607

RESUMO

2D materials have shown great potential as electrode materials that determine the performance of a range of electrochemical energy technologies. Among these, 2D copper-based materials, such as Cu-O, Cu-S, Cu-Se, Cu-N, and Cu-P, have attracted tremendous research interest, because of the combination of remarkable properties, such as low cost, excellent chemical stability, facile fabrication, and significant electrochemical properties. Herein, the recent advances in the emerging 2D copper-based materials are summarized. A brief summary of the crystal structures and synthetic methods is started, and innovative strategies for improving electrochemical performances of 2D copper-based materials are described in detail through defect engineering, heterostructure construction, and surface functionalization. Furthermore, their state-of-the-art applications in electrochemical energy storage including supercapacitors (SCs), alkali (Li, Na, and K)-ion batteries, multivalent metal (Mg and Al)-ion batteries, and hybrid Mg/Li-ion batteries are described. In addition, the electrocatalysis applications of 2D copper-based materials in metal-air batteries, water-splitting, and CO2 reduction reaction (CO2 RR) are also discussed. This review also discusses the charge storage mechanisms of 2D copper-based materials by various advanced characterization techniques. The review with a perspective of the current challenges and research outlook of such 2D copper-based materials for high-performance energy storage and conversion applications is concluded.

9.
Small ; 19(50): e2303884, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37625077

RESUMO

Metal-organic frameworks (MOFs) can be customized through modular assembly to achieve a wide range of potential applications, based on their desired functionality. However, most of the initially reported MOFs are limited to microporous systems and are not sufficiently stable, which restricts their popularization. Heterogeneity is introduced into a simple MOF framework to create MOF-based heterostructures with fascinating properties and interesting functions. Heterogeneity can be introduced into the MOFs via postsynthetic/ligand exchange. Although the ligand exchange has shown potential, it is difficult to precisely control the degree of exchange or position. Among the various synthesis strategies, hierarchical assembly is particularly attractive for constructing MOF-based heterostructures, as it can achieve precise regulation of MOF-based heterostructured nanostructures. The hierarchical assembly significantly expands the compositional diversity of MOF-based heterostructures, which has high elasticity for lattice matching during the epitaxial growth of MOFs. This review focuses on the synthetic evolution mechanism of hierarchical assemblies of MOF-based nanoarchitectures. Subsequently, the precise control of pore structure, pore size, and morphology of MOF-based nanoarchitectures by hierarchical assembly is emphasized. Finally, possible solutions to address the challenges associated with heterogeneous interfaces are presented, and potential opportunities for innovative applications are proposed.

10.
Small ; 19(27): e2207437, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36978243

RESUMO

Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu2+ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.


Assuntos
Hemostáticos , Animais , Hemostáticos/farmacologia , Antioxidantes/farmacologia , Hidrogéis , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Catecóis , Hemostasia
11.
Amino Acids ; 55(10): 1417-1428, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37726574

RESUMO

Acne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC-MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.


Assuntos
Acne Vulgar , Resistência à Insulina , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Metabolômica , Acne Vulgar/epidemiologia
12.
Mediators Inflamm ; 2023: 1257615, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37545738

RESUMO

Background: Sepsis mortality and morbidity are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome. Published studies have discovered that hyperoside (HYP) has an anti-inflammatory and therapeutic effect in many diseases. However, whether HYP treatment can attenuate sepsis-induced ALI is still obscure. Methods: In this study, a cecal ligation and puncture (CLP)-induced sepsis mouse model was constructed. The mouse lungs were harvested and assessed using proteomics, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay for pro-inflammatory cytokines. Human lung microvascular endothelial cells (HLMVECs) were induced with lipopolysaccharide (LPS) for the in vitro model. Results: The results showed that HYP treatment attenuated sepsis-induced ALI through an increased survival rate, decreased inflammatory factor expression, and lung tissue apoptosis. At the same time, HYP pretreatment restored angiogenesis in CLP-induced mouse lung tissues. Proteomics detection showed that Atg13 played a vital role in HYP-mediated protection against sepsis-induced ALI. The in vitro experiment showed HYP treatment attenuated LPS-induced HLMVEC damage by regulating Atg13-mediated autophagy. Inhibiting autophagy or silencing Atg13 reversed the protective effect of HYP against sepsis-induced ALI. Conclusion: Taken together, we conclude that HYP attenuated sepsis-induced ALI by regulating autophagy and inhibiting inflammation.


Assuntos
Lesão Pulmonar Aguda , Sepse , Camundongos , Humanos , Animais , Lipopolissacarídeos/metabolismo , Células Endoteliais/metabolismo , Lesão Pulmonar Aguda/metabolismo , Pulmão/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Autofagia
13.
J Environ Manage ; 342: 118145, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37210817

RESUMO

Monitoring long-term variations in fine particulate matter (PM2.5) is essential for environmental management and epidemiological studies. While satellite-based statistical/machine-learning methods can be used for estimating high-resolution ground-level PM2.5 concentration data, their applications have been hindered by limited accuracy in daily estimates during years without PM2.5 measurements and massive missing values due to satellite retrieval data. To address these issues, we developed a new spatiotemporal high-resolution PM2.5 hindcast modeling framework to generate the full-coverage, daily, 1-km PM2.5 data for China for the period 2000-2020 with improved accuracy. Our modeling framework incorporated information on changes in observation variables between periods with and without monitoring data and filled gaps in PM2.5 estimates induced by satellite data using imputed high-resolution aerosol data. Compared to previous hindcast studies, our method achieved superior overall cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.90 and 12.94 µg/m3 and significantly improved the model performance in years without PM2.5 measurements, raising the leave-one-year-out CV R2 [RMSE] to 0.83 [12.10 µg/m3] at a monthly scale (0.65 [23.29 µg/m3] at a daily scale). Our long-term PM2.5 estimates show a sharp decline in PM2.5 exposure in recent years, but the national exposure level in 2020 still exceeded the first annual interim target of the 2021 World Health Organization air quality guidelines. The proposed hindcast framework represents a new strategy to improve air quality hindcast modeling and can be applied to other regions with limited air quality monitoring periods. These high-quality estimates can support both long- and short-term scientific research and environmental management of PM2.5 in China.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Poluição do Ar/análise , China , Aerossóis/análise
14.
Small ; 18(50): e2205101, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36285775

RESUMO

The design and development of advanced energy storage devices with good energy/power densities and remarkable cycle life has long been a research hotspot. Metal-ion hybrid capacitors (MHCs) are considered as emerging and highly prospective candidates deriving from the integrated merits of metal-ion batteries with high energy density and supercapacitors with excellent power output and cycling stability. The realization of high-performance MHCs needs to conquer the inevitable imbalance in reaction kinetics between anode and cathode with different energy storage mechanisms. Featured by large specific surface area, short ion diffusion distance, ameliorated in-plane charge transport kinetics, and tunable surface and/or interlayer structures, 2D nanomaterials provide a promising platform for manufacturing battery-type electrodes with improved rate capability and capacitor-type electrodes with high capacity. In this article, the fundamental science of 2D nanomaterials and MHCs is first presented in detail, and then the performance optimization strategies from electrodes and electrolytes of MHCs are summarized. Next, the most recent progress in the application of 2D nanomaterials in monovalent and multivalent MHCs is dealt with. Furthermore, the energy storage mechanism of 2D electrode materials is deeply explored by advanced characterization techniques. Finally, the opportunities and challenges of 2D nanomaterials-based MHCs are prospected.

15.
Pharmacol Res ; 181: 106263, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35597383

RESUMO

Glomerulonephritis is a key factor in leading to end-stage renal disease. Mesangial cell proliferation and macrophage infiltration are two prominent features linked in a vicious circle mechanism for glomerulonephritis progression. Herein, a novel biomimetic pH-sensitive nanomicelle (MM/HA-DXM) was constructed to synergize hyaluronic acid (HA)-activated macrophage phenotypic remodeling and dexamethasone (DXM)-mediated mesangial cell killing for precise treatment of glomerulonephritis. Owing to the camouflaged coating with endogenous macrophage membrane (MM), MM/HA-DXM could escape from RES phagocytosis and then be recruited to inflammatory glomerulus by active homing effect. Afterwards, HA-DXM nanomicelles ruptured in response to the weakly acidic glomerulonephritis microenvironment, to locally release HA and DXM. On the one hand, DXM can inhibit the abnormal proliferation of mesangial cells. On the other hand, HA transformed pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotype to improve the glomerular inflammatory microenvironment. In doxorubicin-induced glomerulonephritis models, results revealed that MM/HA-DXM could specifically "homing" to inflammatory renal tissue with 4.33-fold improvement in targeting performance. In addition, in vivo pharmacodynamic results proved that after treatment with MM/HA-DXM, the proteinuria level decreased to 2.33 times, as compared with that of control group, demonstrating a superior therapeutic effect on glomerulonephritis via this collaborative two-pronged anti-inflammatory therapy strategy.


Assuntos
Glomerulonefrite , Micelas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Biomimética , Glomerulonefrite/tratamento farmacológico , Humanos , Glomérulos Renais
16.
J Cardiovasc Pharmacol ; 80(5): 700-708, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35976148

RESUMO

ABSTRACT: To update the efficacy and safety of short-term (≤3 months) dual antiplatelet therapy (DAPT) and standard (6-12 months) DAPT in patients undergoing percutaneous coronary intervention. In addition, we also explored the duration of DAPT in patients at high bleeding risk (HBR). In PubMed, Embase, and Cochrane Library, we electronically searched among all the studies from the establishment of the database to December 8, 2021, for randomized controlled trials (RCTs). Nine randomized controlled trials (45,661 patients) ultimately met the inclusion criteria. The pooled analysis revealed that, compared with standard DAPT, ≤3-month DAPT significantly reduced major adverse cardiovascular event {hazard ratio (HR) = 0.89, 95% confidence interval (CI) [0.82-0.97]}, all-cause mortality [HR = 0.88, 95% CI (0.78-0.99)], cardiovascular mortality [HR = 0.79, 95% CI (0.65-0.97)], major bleeding [HR = 0.72, 95% CI (0.56-0.93)], and any bleeding [HR = 0.57, 95% CI (0.50-0.66)], while no significant differences in the risk of myocardial infarction, stent thrombosis, and stroke. In patients with HBR, the results showed that ≤3-month DAPT significantly reduced major bleeding [HR = 0.35, 95% CI (0.14-0.88)] and any bleeding [HR = 0.53, 95% CI (0.41-0.67)] compared with standard DAPT, while the risk of other outcomes was not statistically different. In conclusion, this study showed that ≤3-month DAPT may be a valid option for most patients after percutaneous coronary intervention. Because reductions in major adverse cardiovascular event, all-cause mortality, and cardiovascular mortality were not seen in patients with HBR, this also highlights the need for specific studies in these patients about optimal duration of antiplatelet therapy.


Assuntos
Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Quimioterapia Combinada , Stents Farmacológicos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Nanotechnology ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35045400

RESUMO

Hierarchical α-MnO2 nanowires with oxygen vacancies grown on carbon fiber have been synthesized by a simple hydrothermal method with the assistance of Ti4+ ions. Ti4+ ions play an important role in controlling the morphology and crystalline structure of MnO2. The morphology and structure of the as-synthesized MnO2 could be tuned from δ-MnO2 nanosheets to hierarchical α-MnO2 nanowires with the help of Ti4+ ions. Based on its fascinating properties, such as many oxygen vacancies, high specific surface area and the interconnected porous structure, the α-MnO2 electrode delivers a high specific capacitance of 472 F g-1 at a current density of 1 A g-1 and the rate capability of 57.6% (from 1 to 16A g-1). The assembled symmetric supercapacitor based on α-MnO2 electrode exhibits remarkable performance with a high energy density of 44.5 Wh kg-1 at a power density of 2.0 kW kg-1 and good cyclic stability (92.6% after 10000 cycles). This work will provide a reference for exploring and designing high-performance MnO2 materials.

18.
Acta Pharmacol Sin ; 43(12): 3096-3111, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36229602

RESUMO

Natural products (NPs) and their structural analogs represent a major source of novel drug development for disease prevention and treatment. The development of new drugs from NPs includes two crucial aspects. One is the discovery of NPs from medicinal plants/microorganisms, and the other is the evaluation of the NPs in vivo at various physiological and pathological states. The heterogeneous spatial distribution of NPs in medicinal plants/microorganisms or in vivo can provide valuable information for drug development. However, few molecular imaging technologies can detect thousands of compounds simultaneously on a label-free basis. Over the last two decades, mass spectrometry imaging (MSI) methods have progressively improved and diversified, thereby allowing for the development of various applications of NPs in plants/microorganisms and in vivo NP research. Because MSI allows for the spatial mapping of the production and distribution of numerous molecules in situ without labeling, it provides a visualization tool for NP research. Therefore, we have focused this mini-review on summarizing the applications of MSI technology in discovering NPs from medicinal plants and evaluating NPs in preclinical studies from the perspective of new drug research and development (R&D). Additionally, we briefly reviewed the factors that should be carefully considered to obtain the desired MSI results. Finally, the future development of MSI in new drug R&D is proposed.


Assuntos
Produtos Biológicos , Espectrometria de Massas/métodos , Plantas , Pesquisa , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
19.
Environ Res ; 215(Pt 2): 114261, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096172

RESUMO

Long-term exposure to air pollution is associated with a higher risk of cognitive impairment; however, the understanding of this association is incomplete. We aimed to explore the relationship between fine particulate matter (PM2.5) exposure and cognitive function using a prospective cohort of ageing adults, including 19,389 respondents in four waves of the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018) linked with the historical PM2.5 concentrations (2000-2018) in China. By extending the measurement of PM2.5 exposure from exposure intensity (averaged PM2.5 concentrations) to exposure duration (the number of months with higher PM2.5 concentrations), we employed two linear models, the fixed-effect and mixed-effect linear models, to estimate the associations between PM2.5 exposure and cognitive impairment, with adjustments for individual and regional covariates. Our findings show that the higher PM2.5 intensity was associated with worse cognitive function, but the associations were only statistically significant in a longer exposure period (more than one year), especially in the 10-year exposure (Coefficient: -0.13; 95% Confidence Interval: -0.22, -0.04). Similar patterns were seen for fully adjusted models of PM2.5 duration: a longer duration in PM2.5 exposure was associated with lower cognitive scores, and the duration with higher cut-off points had stronger effects on cognitive function except for the duration at 75 µg/m3, suggesting a possible coincidence of increasing air pollution and economic development. The stronger exposure to PM2.5 was associated with poorer cognitive function among Chinese adults, while more work is necessary to explore the causal effect of air pollution, independent of individual and contextual background characteristics.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Disfunção Cognitiva , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/epidemiologia , Exposição Ambiental/análise , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Material Particulado/análise , Material Particulado/toxicidade , Estudos Prospectivos
20.
Oral Dis ; 28(7): 1936-1946, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33715257

RESUMO

OBJECTIVE: To develop an in vivo model to simulate the complex internal environment of diabetic peri-implantitis (T2DM-PI) model for a better understanding of peri-implantitis in type 2 diabetic patients. MATERIALS AND METHODS: Maxillary first molars were extracted in Sprague-Dawley (SD) rats, and customized cone-shaped titanium implants were installed in the extraction sites. Thereafter, implants were uncovered and customized abutments were screwed into implants. A high-fat diet and a low-dose injection of streptozotocin were utilized to induce T2DM. Finally, LPS was locally injected in implant sulcus to induce peri-implantitis. RESULTS: In the present study, T2DM-PI model has been successfully established. Imaging analysis revealed that abundant inflammatory cells infiltrated in the soft tissue in T2DM-PI group with concomitant excessive secretion of inflammatory cytokines. Moreover, higher expression of MMP and increased number of osteoclasts led to collagen disintegration and bone resorption in T2DM-PI group. CONCLUSIONS: These results describe a novel rat model which stimulate T2DM-PI in vivo, characterized by overwhelming inflammatory response and bone resorption. This model has a potential to be used for investigation of initiation, progression and interventional therapy of T2DM-PI.


Assuntos
Reabsorção Óssea , Implantes Dentários , Diabetes Mellitus Tipo 2 , Peri-Implantite , Animais , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/complicações , Peri-Implantite/etiologia , Ratos , Ratos Sprague-Dawley
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