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1.
Biomaterials ; 313: 122771, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39190940

RESUMO

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.


Assuntos
Fluorocarbonos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Microambiente Tumoral , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Camundongos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos Endogâmicos BALB C , Terapia Fototérmica/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fototerapia/métodos , Feminino
2.
Biol Trace Elem Res ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312125

RESUMO

This study aims to elucidate the role of silent information regulator 2 homologue 1 (SIRT1) in cartilage damage in Kashin-Beck disease (KBD) by exploring the correlation between SIRT1 and KBD and the potential effect of SIRT1 expression and methylation on chondrocyte apoptosis. SIRT1 protein expression was detected using IHC, and the mRNA levels of SIRT1, DNMTs, and apoptosis-related genes were measured by RT-qPCR. Methylation levels of SxIRT1 were detected by MALDI-TOF-MS, MSP, and qMSP. Chondrocyte apoptosis was determined by Hoechst 33,342 staining and Annexin V-FITC/PI following selenium (Se) deficiency or T-2 toxin and Se supplement. Both protein and mRNA levels of SIRT1 were reduced in KBD patients, and SIRT1 expression discriminated between KBD and non-KBD with an AUC greater than 0.7. Methylation levels of SIRT1 were significantly elevated in KBD patients, and SIRT1 hypermethylation increased the risk of acquiring KBD 3.879-fold. DNMTs mRNA levels were increased in KBD patients, and further, DNMT1 mRNA levels were decreased, and SIRT1 mRNA levels were increased in the SIRT1 hypomethylation group. Moreover, the SIRT1 expression was negatively correlated with pro-apoptotic genes and positively correlated with anti-apoptotic gene expression, especially in KBD patients. Furthermore, apoptosis rates, DNMT1 mRNA level, and SIRT1 methylation level were increased in chondrocytes treated with Se deficiency and T-2 toxin, but SIRT1 mRNA level was downregulated, whereas the opposite trend was observed in chondrocytes treated with Se supplement. Low SIRT1 expression and CpG hypermethylation in KBD patients are associated with increased disease risk, which mediated chondrocyte apoptosis can be ameliorated by Se supplement.

3.
Foods ; 13(17)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39272434

RESUMO

Ganoderma lucidum (GL) is a kind of edible fungus with various functions and a precious medicinal material with a long history. Ganoderma lucidum polysaccharide (GLP) is one of the main bioactive substances in GL, with anti-tumor, anti-oxidation, anti-cancer, and other biological activities. GLP is closely related to human health, and the research on GLP is getting deeper. This paper reviewed the extraction and purification methods of GLP, the relationship between structure and activity, and the qualitative and quantitative methods. This review provides solutions for the analysis and application of GLP. At the same time, some new methods for extraction, purification and analysis of GLP, the relationship between advanced structures and activity, and future applications of and research into GLP were emphasized. As a kind of bioactive macromolecule, GLP has unique functional properties. Through the comprehensive summary of the extraction, purification, and analysis of GLP and its future prospects, we hope that this review can provide valuable reference for the further study of GLP.

4.
Plants (Basel) ; 13(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39273893

RESUMO

Soil salinization significantly impacts the ecological environment and agricultural production, posing a threat to plant growth. Currently, there are over 400 varieties of Bougainvillea with horticultural value internationally. However, research on the differences in salt tolerance among Bougainvillea varieties is still insufficient. Therefore, this study aims to investigate the physiological responses and tolerance differences of various Bougainvillea varieties under different concentrations of salt stress, reveal the effects of salt stress on their growth and physiology, and study the adaptation mechanisms of these varieties related to salt stress. The experimental materials consisted of five varieties of Bougainvillea. Based on the actual salinity concentrations in natural saline-alkali soils, we used a pot-controlled salt method for the experiment, with four treatment concentrations set: 0.0% (w/v) (CK), 0.2% (w/v), 0.4% (w/v), and 0.6% (w/v). After the Bougainvillea plants grew stably, salt stress was applied and the growth, physiology, and salt tolerance of the one-year-old plants were systematically measured and assessed. The key findings were as follows: Salt stress inhibited the growth and biomass of the five varieties of Bougainvillea; the 'Dayezi' variety showed severe salt damage, while the 'Shuihong' variety exhibited minimal response. As the salt concentration and duration of salt stress increase, the trends of the changes in antioxidant enzyme activity and osmotic regulation systems in the leaves of the five Bougainvillea species differ. Membrane permeability and the production of membrane oxidative products showed an upward trend with stress severity. The salt tolerance of the five varieties of Bougainvillea was comprehensively evaluated through principal component analysis. It was found that the 'Shuihong' variety exhibited the highest salt tolerance, followed by the 'Lvyehuanghua', 'Xiaoyezi', 'Tazi', and 'Dayezi' varieties. Therefore, Bougainvillea 'Shuihong', 'Lvyehuanghua', and 'Xiaoyezi' are recommended for extensive cultivation in saline-alkali areas. The investigation focuses primarily on how Bougainvillea varieties respond to salt stress from the perspectives of growth and physiological levels. Future research could explore the molecular mechanisms behind the responses to and tolerance of different Bougainvillea varieties as to salt stress, providing a more comprehensive understanding and basis for practical applications.

5.
Mar Pollut Bull ; 208: 116999, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39305843

RESUMO

During the spring and summer of 2021, two investigations were conducted in the northern Chinese sea by using the high-performance liquid chromatography with the pigment-based chemotaxonomic tool PIGMENTUM. Results showed that the average chlorophyll a (Chl a) concentration during spring was significantly higher (p < 0.01) than that during summer. 19'-hexanoyloxyfucoxanthin-containing algae, alloxanthin-containing algae (ACA), and fucoxanthin-containing algae (FCA) were the main pigment groups in spring, whereas zeaxanthin-containing algae (ZCA) and peridinin-containing algae (PeCA) were dominated in summer. Five ecological provinces were divided, and the phytoplankton biomass (Chl a) in Province V was the lowest. Redundancy analysis showed that ACA, FCA, and PeCA were positively correlated with nutrients; in comparison, ZCA preferred high salinity. The PIGMENTUM estimates were significantly positively correlated (p < 0.01) with CHEMTAX for all phytoplankton assemblages. Nevertheless, the coefficients of determination and slope by regression analysis between two methods showed large differences for several phytoplankton groups.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39307933

RESUMO

BACKGROUND: Sex differences in blood pressure (BP) levels and hypertension are important and the role of socioeconomic status (SES) in sex differences of hypertension remains unclear. OBJECTIVE: We aimed to evaluate the impact of SES on sex differences of hypertension in a nationally representative survey study. METHODS: A total of 98,658 participants aged ≥18 years who have lived in their current residence for ≥6 months were recruited from 162 study sites across mainland China. Sex was self-reported. Individual-level SES included the highest level of education and annual household income. Area-level SES included economic development status, urban/rural residency, and north/south location. Outcomes included levels of systolic and diastolic BP, and hypertension. Linear and Cox regression models were used to examine the associations between sex (women vs. men) and BP characteristics stratified by individual or combined SES indicators. RESULTS: Systolic and diastolic BP levels and prevalence of hypertension were higher in men than women. This sex difference was found across categories of SES with widened sex disparities in participants having more favorable SES. Significant multiplicative interaction effects of SES on the association of sex with BP characteristics were found. Women with improving SES were associated with lower BP and hypertension prevalence compared with men. For combined SES, a 9% (prevalence ratio (PR)=0.91, 95% confidence interval (CI)=0.83, 0.98) and a 30% lower probability (PR=0.70, 95% CI=0.63, 0.78) of having hypertension were found in women with an overall intermediate SES and high SES, respectively compare with low SES while no significant reduction was found in men. CONCLUSIONS: There are significant sex differences in BP characteristics and SES has a potent impact on the disparities. Sex-specific public health policies to alleviate socioeconomic inequalities, especially in women are important for the prevention of hypertension.

7.
J Agric Food Chem ; 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39308150

RESUMO

A new method for rapid and facile fabrication of homoporous films with high volatile amine sensitivity was developed. First, red cabbage anthocyanin was encapsulated in ethyl cellulose to form water-in-organic (W/O) emulsion. Afterward, the W/O emulsion was rapidly dried using the supporting matrix Magnolia Grandiflora Linn leaf vein at 60% relative humidity and 50 °C to form a colorimetric film with regular hexagonal pores with an average side length of about 23 µm. The films exhibited good sensitivity to ammonia (NH3), dimethylamine, and trimethylamine, with limit of detection of 0.26, 0.24, and 0.38 µM, respectively, and high stability when stored in high humid environments. An obvious color change of the films from pink to green was clearly observed during the freshness monitoring of pork, chicken, salmon, and shrimp. Thus, this work offered a novel and reliable method for the development of porous films for food freshness monitoring.

8.
Theriogenology ; 229: 214-224, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39217650

RESUMO

Vitrification of oocyte has become an important component of assisted reproductive technology and has important implications for animal reproduction and the preservation of biodiversity. However, vitrification adversely affects mitochondrial function and oocyte developmental potential, mainly because of oxidative damage. Rutin is a highly effective antioxidant, but no information is available to the effect of rutin on the mitochondrial function and development in vitrified oocytes. Therefore, we studied the effects of rutin supplementation of vitrification solution on mitochondrial function and developmental competence of ovine germinal vesicle (GV) stage oocytes post vitrification. The results showed that supplementation of vitrification solution with 0.6 mM rutin significantly increased the cleavage rate (71.6 % vs. 59.3 %) and blastocyst rate (18.9 % vs. 6.8 %) compared to GV-stage oocytes in the vitrified group. Then, we analyzed the reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and membrane potential (ΔΨm), endoplasmic reticulum (ER) Ca2+, and annexin V (AV) of vitrified sheep GV-stage oocytes. Vitrified sheep oocytes exhibited increased levels of ROS and Ca2+, higher rate of AV-positive oocytes, and decreased mitochondrial activity, GSH and ΔΨm levels. However, rutin supplementation in vitrification solution decreased the levels of ROS, Ca2+ and AV-positive oocytes rate, and increased the GSH and ΔΨm levels in vitrified oocytes. Results revealed that rutin restored mitochondrial function, regulated Ca2+ homeostasis and decreased apoptosis potentially caused by mitophagy in oocytes. To understand the mechanism of rutin functions in vitrified GV-stage oocytes in sheep, we analyzed the transcriptome and found that rutin mediated oocytes development and mitochondrial function, mainly by affecting oxidative phosphorylation and the mitophagy pathways. In conclusion, supplementing with 0.6 mM rutin in vitrification solution significantly enhanced developmental potential through improving mitochondrial function and decreased apoptosis potentially caused by mitophagy after vitrification of ovine GV-stage oocytes.


Assuntos
Criopreservação , Mitocôndrias , Oócitos , Rutina , Vitrificação , Animais , Rutina/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Ovinos/fisiologia , Mitocôndrias/efeitos dos fármacos , Vitrificação/efeitos dos fármacos , Criopreservação/veterinária , Espécies Reativas de Oxigênio/metabolismo , Feminino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Antioxidantes/farmacologia , Desenvolvimento Embrionário/efeitos dos fármacos
9.
Mar Environ Res ; 202: 106734, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244953

RESUMO

Laizhou Bay, a major breeding ground for economic marine organisms in the northern waters of China, is facing rapid environmental degradation. In this study, field surveys in this area were conducted in the spring, summer, and autumn of 2020. Microscopic observation and RuBisCO large subunit (rbcL) gene analysis were employed to understand the community structure and temporal dynamics of phytoplankton. The phytoplankton community structures detected by the two methods showed significant differences. Microscopic observation revealed the dominance of dinoflagellates in spring that shifted to the dominance of diatoms in summer and autumn. However, rbcL gene sequencing consistently identified diatoms as dominant throughout all three seasons, with their relative abundance showing an increasing trend. Conversely, the relative abundance of the second- and third-most abundant taxa, namely, haptophytes and ochrophytes, decreased as the seasons transitioned. rbcL gene sequencing annotated more species than microscopy. It could detect haptophytes and cryptophytes, which were overlooked by microscopy. In addition, rbcL gene sequencing detected a remarkable amount of Thalassiosira profunda, which was previously unidentified in this sea area. However, it appeared to underestimate the contribution of dinoflagellates considerably, with most taxa being only identified through microscopic identification. The two methods jointly identified 28 harmful algal bloom taxa with similar detection quantities but substantial differences in species composition. Phytoplankton communities were influenced by temperature, salinity, and nutrients. The results of this work suggest that a combination of multiple techniques is necessary for a comprehensive understanding of phytoplankton.

10.
Chem Sci ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39268208

RESUMO

Room-temperature ferromagnetism in graphene has attracted considerable attention due to its potential application as spintronics. Theoretically, magnetic moment of graphene can be generated by removing a single pz orbital from the π system, which introduces an unpaired electron into the graphene motif for magnetic coupling. In this work, pz orbital of graphene is experimentally removed by cleaving the π bond of graphene using H3BO3 with the assistance of supercritical CO2 (SC CO2), which simultaneously introduces -B(OH)2 groups and unpaired electrons. As a result, ferromagnetic coupling between unpaired electrons substantially enhances the magnetic properties of the 2D graphene motif, leading to room-temperature ferromagnetism. Overall, unpaired electrons were introduced into a 2D graphene motif through π bond cleavage, which provides a novel approach for magnetic manipulation of 2D materials with conjugated structures.

11.
Food Chem X ; 24: 101801, 2024 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-39290751

RESUMO

Ratiometric fluorescent films with high amine sensitivity and stability were developed to monitor the freshness of beef and pork. Fluorescein isothiocyanate (FITC) and red carbon quantum dots (R-CQD) were used as the amine-responsive indicator and internal reference, respectively. The electrospun films prepared by immobilizing FITC and R-CQD complex (F-R) into polyvinylidene fluoride (PVDF) under 35 %, 55 % and 75 % of relative humidity (RH) were named F-R@PVDF-1, F-R@PVDF-2 and F-R@PVDF-3, respectively. In comparison, the F-R@PVDF-2 film exhibited the highest sensitivity to trimethylamine (TMA), demonstrating a limit of detection (LOD) value of 1.59 µM, and meanwhile high stability during storage with ΔE value of 1.99 after 14 days of storage at 4 °C. The F-R@PVDF-2 film also showed a significant fluorescent red-to-brown color change during meat freshness monitoring at 4 °C. Conclusively, this study reported a new ratiometric fluorescent film that can be used to track the freshness of meats in food packaging.

12.
J Hazard Mater ; 480: 135847, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39288521

RESUMO

The rising prevalence of antibiotic resistance genes (ARGs) in the surface waters of lakes poses a significant threat to human health. The overlying water in these lakes serves as a critical hotspot for the accumulation of ARGs in surface water. However, the mobility of extracellular (adsorbed ARGs (a-eARGs) and free ARGs (f-eARGs)), and intracellular ARGs (i-ARGs) from overlying water to surface water remains unknown. This study examined the mobility of ARGs between water layers, as well as the underlying mechanisms involved. Significant variations in ARG abundance were observed between overlying and surface water according to PCoA analysis (p < 0.05), with significant reductions in i-ARGs (p < 0.05) in surface water and no significant difference in a-eARGs and f-eARGs. Aminoglycoside and tetracycline i-ARGs had the highest and lowest mobility from overlying water to surface water, respectively. Additionally, the transformation of i-ARGs from overlying water to surface water was significantly correlated with total phosphorus ratio. According to the direct analysis of partial least squares-path modeling, the key drivers of a- and f-eARGs movement from overlying water to surface water were free-living and particle-attached bacteria, respectively, whereas heavy metals gradually became the driving force for i-ARGs by regulating mobile genetic elements. This study illustrated the transmission mechanisms of ARGs from overlying water to surface water in lakes, which will be useful for ARG treatment strategies, especially in eutrophic water.

13.
Neuropharmacology ; 261: 110158, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276863

RESUMO

Migraine is a highly prevalent neurological disorder. Alpha-asarone (ASA), a major active component found in Acorus tatarinowii, plays a crucial role in analgesia and anti-inflammation for neuropathic pain. This study aimed to assess the efficacy of ASA against migraine and elucidate its potential mechanisms using a well-established inflammatory soup (IS) migraine female rat model. Mechanical pain thresholds were assessed daily before IS infusion, followed by post-infusion administration of ASA. Subsequently, spontaneous locomotor activities, exploratory behavior, short-term spatial memory, and photophobia were blindly evaluated after the final drug administration. The rats were then sacrificed for investigation into the underlying mechanisms of action. Network pharmacology was also employed to predict potential targets and pathways of ASA against migraine. The anti-inflammatory activity of ASA and pathway-related proteins were examined in BV2 cells stimulated with lipopolysaccharides (LPS). The results demonstrated that ASA ameliorated cutaneous hyperalgesia and photophobia while improving spatial memory and increasing exploratory behavior in IS rats. ASA attenuated central sensitization-related indicators and excessive glutamate levels while enhancing GABA synthesis. ASA rescued neuronal loss in the cortex and hippocampus of IS rats. Notably, the ability of ASA to improve spatial memory performance in the Y maze test was not observed with sumatriptan, a first-line treatment drug, suggesting the potential involvement of the TLR4 pathway. Moreover, ASA suppressed microglial activation, reduced pro-inflammatory factors, and downregulated TLR4, MyD88, p-NF-κB/NF-κB, NLRP3, caspase-1, IL-1ß, and IL-18. Overall, ASA demonstrated its potential to alleviate hyperalgesia and improve behavioral performance in migraine rats by inhibiting hyperexcitability and microglia-related inflammation.

14.
Proc Natl Acad Sci U S A ; 121(37): e2314337121, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39226363

RESUMO

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.


Assuntos
Doença de Alzheimer , Neoplasias Colorretais , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Animais , Doença de Alzheimer/microbiologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Camundongos , Humanos , Masculino , Inflamação , Disfunção Cognitiva , Feminino , Prevotella , Modelos Animais de Doenças , Lipopolissacarídeos , Carcinogênese , Sulfato de Dextrana
15.
Ecotoxicol Environ Saf ; 285: 117064, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39299205

RESUMO

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1-101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

16.
Acta Biomater ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299625

RESUMO

The gut is a vital organ that is central to the absorption and metabolic processing of orally administered drugs. While there have been many models developed with the goal of studying the absorption of drugs in the gut, these models fail to adequately recapitulate the diverse, complex gastrointestinal microenvironment. The recent emergence of microfluidic organ-on-a-chip technologies has provided a novel means of modeling the gut, yielding radical new insights into the structure of the gut and the mechanisms through which it shapes disease, with key implications for biomedical developmental efforts. Such organ-on-a-chip technologies have been demonstrated to exhibit greater cost-effectiveness, fewer ethical concerns, and a better ability to address inter-species differences in traditional animal models in the context of drug development. The present review offers an overview of recent developments in the reconstruction of gut structure and function in vitro using microfluidic gut-on-a-chip (GOC) systems, together with a discussion of the potential applications of these platforms in the context of drug development and the challenges and future prospects associated with this technology. STATEMENT OF SIGNIFICANCE: This paper outlines the characteristics of the different cell types most frequently used to construct microfluidic gut-on-a-chip models and the microfluidic devices employed for the study of drug absorption. And the applications of gut-related multichip coupling and disease modelling in the context of drug development is systematically reviewed. With the detailed summarization of microfluidic chip-based gut models and discussion of the prospective directions for practical application, this review will provide insights to the innovative design and application of microfluidic gut-on-a-chip for drug development.

17.
Heliyon ; 10(17): e36890, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39281542

RESUMO

Background: Extracellular vesicles (EVs) are being considered as a potential therapeutic option for ulcerative colitis (UC), and numerous preclinical studies have been conducted on the use of EVs for UC. Methods: A systematic review was conducted to compare the therapeutic effects of mammalian EVs and placebo on UC in animal models, along with a meta-analysis comparing naïve (unmodified) EVs and placebo. The search was performed in four databases (PubMed, Web of Science, Scopus, and EMBASE) up to September 13th, 2023. The primary outcomes included disease activity index (DAI), colonic mucosal damage index (CMDI), and adverse effects (PROSPERO ID: CRD42023458039). Results: A total of 69 studies were included based on pre-determined criteria, involving 1271 animals. Of these studies, 51 measured DAI scores, with 98 % reporting that EVs could reduce DAI scores. Additionally, 5 studies reported CMDI and all showed that EVs could significantly reduce CMDI. However, only 3 studies assessed adverse effects and none reported any significant adverse effects. The meta-analysis of these studies (40 studies involving 1065 animals) revealed that naïve EVs could significantly decrease the DAI score (SMD = -3.00; 95 % CI: -3.52 to -2.48) and CMDI (SMD = -2.10; 95 % CI: -2.85 to -1.35). Conclusion: The results indicate that mammalian EVs have demonstrated therapeutic benefits in animal models of UC; however, the safety profile of EVs remains inadequate which highlights the need for further research on safety outcomes.

18.
J Natl Cancer Cent ; 4(3): 223-232, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39281725

RESUMO

Objective: To analyze the impact of global population aging on cancer epidemiology, with a focus on the incidence and mortality rates among individuals aged 60 years and above. Methods: We utilized open-source data, retrieving population age estimates from the United Nations Population Division website. The GLOBOCAN 2020 database provided estimates for cancer cases and deaths in 2020 and 2040, while the Global Burden of Disease 2019 database supplied estimates of new cancer cases worldwide from 2000 to 2019. Inclusion criteria considered individuals aged 60 years and over, focusing on the top five deadliest cancers. The cohort-component method was employed for population prediction, with age-specific incidence and mortality rates estimated for 2020 used to forecast the cancer burden. Results: In 2021, the global population aged over 60 years accounted for 13.7%, with Europe/North America and Australia/New Zealand having the highest proportions. The older population is predicted to reach 19.2% by 2040. In 2020, of the 19.3 million new cancer cases worldwide, 64% occurred in individuals aged 60 and above, contributing to 71.3% of cancer-related deaths. The five most common cancer sites were the lung, colorectum, prostate, breast, and stomach. Cancer incidence and deaths are projected to rise significantly among older individuals, reaching 20.7 million new cases and 12.7 million deaths by 2040. Older age, tobacco use, dietary factors, alcohol consumption, and high body mass index (BMI) were identified as major risk factors for various cancers in this demographic. Conclusions: This study reveals a significant rise in cancer incidence and mortality among the elderly due to global population aging. The urgency for targeted interventions in cancer prevention, screening, and treatment for older individuals is emphasized. Despite acknowledged limitations, these findings contribute valuable insights to inform strategies for managing cancer in the elderly amidst evolving demographic trends.

19.
Adv Mater ; : e2408461, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39285843

RESUMO

Understanding the spin-dependent activity of nitrogen-coordinated single metal atom (M-N-C) electrocatalysts for oxygen reduction and evolution reactions (ORR and OER) remains challenging due to the lack of structure-defined catalysts and effective spin manipulation tools. Herein, both challenges using a magnetic field integrated heterogeneous molecular electrocatalyst prepared by anchoring cobalt phthalocyanine (CoPc) deposited carbon black on polymer-protected magnet nanoparticles, are addressed. The built-in magnetic field can shift the Co center from low- to high-spin (HS) state without atomic structure modification, affording one-order higher turnover frequency, a 50% increased H2O2 selectivity for ORR, and a ≈4000% magnetocurrent enhancement for OER. This catalyst can significantly minimize magnet usage, enabling safe and continuous production of a pure H2O2 solution for 100 h from a 100 cm2 electrolyzer. The new strategy demonstrated here also applies to other metal phthalocyanine-based catalysts, offering a universal platform for studying spin-related electrochemical processes.

20.
Mar Pollut Bull ; 207: 116880, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39217867

RESUMO

This study investigated the regional, seasonal, and species abundance and characteristics of microplastics (MPs) in bivalves from Qingdao, China and assessed the dietary exposure of MPs through bivalve consumption. The average abundance was 1.17 ± 1.07 items/individual or 0.17 ± 0.22 items/g wet weight. Fiber was the dominant shape (91.5 %). The average size of MPs was 995.63 ± 796.59 µm. Rayon, PE, and PET contributed mostly to the MPs composition. There were no significant regional or seasonal differences in MPs abundance (p > 0.05), while there were significant species differences (p < 0.05) when describing the abundance by wet weight. The estimated daily intakes of MPs through bivalve consumption by general population, consumer only population, and coastal residents in China were 3.32 × 10-3, 0.08, and 0.16 µg/kg BW, respectively. The exposure assessment method by converting the quantity of MPs into mass may facilitate the risk characterization in the future.


Assuntos
Bivalves , Monitoramento Ambiental , Microplásticos , Poluentes Químicos da Água , Animais , China , Microplásticos/análise , Poluentes Químicos da Água/análise
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