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2.
Animals (Basel) ; 14(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612301

RESUMO

In the realm of modern aquaculture, the utilization of probiotics has gained prominence, primarily due to their ability to enhance growth, boost immunity, and prevent diseases in aquatic species. This study primarily investigates the efficacy of Bacillus subtilis strains, both host-derived and from other sources, in influencing fish growth, immunity, lipid metabolism, and disease resistance. Employing a 42-day feeding trial, we divided hybrid grouper into four distinct groups: a control group on a basal diet and three experimental groups supplemented with 1 × 108 CFU/g of different Bacillus subtilis strains-BS, 6-3-1, and HAINUP40. Remarkably, the study demonstrated that the 6-3-1 and HAINUP40 groups exhibited significant enhancements across key growth parameters: final body weight (FBW), weight gain rate (WGR), feed intake (FI), feed efficiency ratio (FER), and feed conversion ratio (FCR). The investigation into lipid metabolism revealed that the 6-3-1 strain upregulated seven metabolism-related genes, HAINUP40 affected four metabolism-related genes, and the BS strain influenced two metabolism-related genes, indicating diverse metabolic impacts by different strains. Further, a notable reduction in liver enzymes AST and ALT was observed across all supplemented groups, implying improved liver health. Noteworthy was the BS strain's superior antioxidative capabilities, positively affecting all four measured parameters (CAT, GSH-Px, MDA). In the sphere of immune-related gene expression, the BS strain significantly decreased the expression of both inflammation and apoptosis-related genes, whereas the HAINUP40 strain demonstrated an upregulation in these genes. The challenge test results were particularly telling, showcasing improved survival rates against Vibrio harveyi infection in the BS and 6-3-1 groups, unlike the HAINUP40 group. These outcomes highlight the strain-specific nature of probiotics and their varying mechanisms of action within the host. In conclusion, this study reveals that probiotic strains, varying by source, demonstrate unique, strain-specific effects in promoting growth and modulating immunity in hybrid grouper. This research highlights the promise of tailored probiotic applications in improving aquaculture practices. Such advancements contribute to more sustainable and efficient fish farming methods.

3.
World J Clin Cases ; 12(11): 1990-1995, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38660553

RESUMO

BACKGROUND: When an anorectal foreign body is found, its composition and shape should be evaluated, and a timely and effective treatment plan should be developed based on the patient's symptoms to avoid serious complications such as intestinal perforation caused by displacement of the foreign body. CASE SUMMARY: A 54-year-old male was admitted to our outpatient clinic on June 3, 2023, due to a rectal foreign body that had been embedded for more than 24 h. The patient reported using a glass electrode tube to assist in the recovery of prolapsed hemorrhoids, however, the electrode tube was inadvertently inserted into the anus and could not be removed by the patient. During hospitalization, the patient underwent surgery, and the foreign body was dragged into the rectum with the aid of colonoscopy. The anus was dilated with a comb-type pulling hook and an anal fistula pulling hook to widen the anus and remove the foreign body, and the local anal symptoms were then relieved with topical drugs. The patient was allowed to eat and drink, and an entire abdominal Computed tomography (CT) and colonoscopy were reviewed 3 d after surgery. CT revealed no foreign body residue and colonoscopy showed no metal or other residues in the colon and rectum, and no apparent intestinal tract damage. CONCLUSION: The timeliness and rationality of the surgical and therapeutic options for this patient were based on a literature review of the clinical signs and conceivable conditions in such cases. The type, material and the potential risks of rectal foreign bodies should be considered.

4.
Heliyon ; 10(7): e28944, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38617957

RESUMO

Background: Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods: We extracted blood eQTL data from the GTExv8.ALL.Whole_Blood database, genome-wide association studies (GWAS) summary statistics of IBD from the IEU GWAS database, and performed a three-fold analysis protocol, including transcriptome-wide association analysis, Mendelian randomisation analysis, Bayesian colocalisation, and subsequent potential therapeutic agents identification. Results: We identified four pathogenic genes, namely CARD9, RTEL1, STMN3 and ARFRP1, that promote the development of IBD, encompassing both ulcerative colitis (UC) and Crohn's disease (CD). Notably, ARFRP1 exhibited the ability to suppress IBD (encompassing UC and CD) development. Regarding drug prediction, cyclophosphamide emerged as a promising novel therapeutic option for IBD, encompassing UC and CD. Conclusion: We identified several potential genes related to IBD (UC and CD), including CARD9, RTEL1, STMN3 and ARFRP1, warranting further investigation in functional studies to elucidate underlying disease mechanisms. Additionally, clinical studies exploring the potential of cyclophosphamide as a treatment avenue for IBD are warranted.

5.
Chem Sci ; 15(13): 4952-4959, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38550696

RESUMO

Due to their sustainability, environmental friendliness, high specific capacity, and rapid reaction kinetics, quinone cathodes have broad application prospects in aqueous zinc-ion batteries (AZIBs). However, conventional small-molecule quinone cathodes usually suffer from unavoidable dissolution, resulting in terrible cycling stability. Herein, based on a strategy of molecular structure optimization, calix[8]quinone (C8Q) is for the first time used as a cathode in AZIBs. By extending the structure of the classical small-molecule quinone cathode calix[4]quinone (C4Q), C8Q further adds four p-benzoquinone structural units, which significantly suppresses the dissolution of its discharge products and greatly improves the cycle stability of the cathode. Specifically, the C8Q cathode displays a discharge specific capacity of 207.2 mA h g-1 at 1 A g-1 and a long-life cycle stability (93 mA h g-1/10 A g-1/10000th). Even with a high active material loading of 11 mg cm-2, the Zn‖C8Q battery also exhibits high redox reversibility and remarkable electrochemical stability. Furthermore, the belt-shaped Zn‖C8Q battery has high stability and outstanding flexibility, indicating its promising application in flexible wearable electronic devices.

6.
Adv Sci (Weinh) ; : e2307660, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491910

RESUMO

Basal-like breast cancer (BLBC) is the most aggressive molecular subtype of breast cancer with worse prognosis and fewer treatment options. The underlying mechanisms upon BLBC transcriptional dysregulation and its upstream transcription factors (TFs) remain unclear. Here, among the hyperactive candidate TFs of BLBC identified by bioinformatic analysis, POU4F1 is uniquely upregulated in BLBC and is associated with poor prognosis. POU4F1 is necessary for the tumor growth and malignant phenotypes of BLBC through regulating G1/S transition by direct binding at the promoter of CDK2 and CCND1. More importantly, POU4F1 maintains BLBC identity by repressing ERα expression through CDK2-mediated EZH2 phosphorylation and subsequent H3K27me3 modification in ESR1 promoter. Knocking out POU4F1 in BLBC cells reactivates functional ERα expression, rendering BLBC sensitive to tamoxifen treatment. In-depth epigenetic analysis reveals that the subtype-specific re-configuration and activation of the bivalent chromatin in the POU4F1 promoter contributes to its unique expression in BLBC, which is maintained by DNA demethylase TET1. Together, these results reveal a subtype-specific epigenetically activated TF with critical role in promoting and maintaining BLBC, suggesting that POU4F1 is a potential therapeutic target for BLBC.

7.
Sci Rep ; 14(1): 7320, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538807

RESUMO

The Ningdong coalfield has played a pivotal role in advancing local economic development and meeting national energy. Nevertheless, mining operations have engendered ecological challenges encompassing subterranean water depletion, land desertification, and ground subsidence, primarily stemming from the disruption of coal seam roof strata. Consequently, the local ecosystem has incurred substantial harm. Water-preserved coal mining presently constitutes the pivotal technology in mitigating this problem. The primary challenge of this technique lies in identifying critical aquifer layers and understanding the heights of water-conducting fracture zones. To obtain a precise comprehension of the seepage patterns within the upper coal seam aquifer during mining, delineate the extent of water-conducting fracture zones, non-invasive geophysical techniques such as time-lapse electrical resistivity tomography (TL-ERT), magnetic resonance sounding (MRS), and spontaneous potential (SP) have been employed to monitor alterations within the shallow coalfield's aquifer throughout the mining process in the Ningdong coalfield. By conducting meticulous examinations of fluctuations in resistivity, moisture content, and self-potential within the superjacent strata during coal seam extraction, the predominant underground water infiltration strata were ascertained, concurrently enabling the estimation of the development elevation of water-conducting fracture zones. This outcome furnishes a geophysical underpinning for endeavors concerning local water-preserved coal mining and ecological rehabilitation.

8.
Ann Hematol ; 103(5): 1775-1777, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556531

RESUMO

Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.


Assuntos
Compostos de Anilina , Doenças da Medula Óssea , Compostos Bicíclicos Heterocíclicos com Pontes , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Pirazinas , Aplasia Pura de Série Vermelha , Sulfonamidas , Humanos , Azacitidina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aplasia Pura de Série Vermelha/etiologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Doenças da Medula Óssea/complicações
9.
Phytomedicine ; 127: 155428, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458086

RESUMO

BACKGROUND: Previous studies have confirmed the antioxidant and anti-inflammatory effects of active ginseng components that protect against liver injury. However, ginseng-derived nanoparticles (GDNPs), low-immunogenicity nanovesicles derived from ginseng, have not been reported to be hepatoprotective. PURPOSE: In this study, we investigated whether GDNPs could attenuate alcohol-induced liver injury in LO2 cells and mice by modulating oxidative stress and inflammatory pathways, thereby advancing the theoretical basis for the development of novel pharmacological treatments. STUDY DESIGN: Alcohol was used to construct in vitro and in vivo models of alcoholic liver injury. To explore the mechanisms by which GDNPs exert their protective effects against alcoholic liver injury, we examined the expression of oxidative stress-related genes and analysed inflammatory responses in vitro and in vivo. The experimental findings were verified using network pharmacology. METHODS: The composition of the GDNPs was analysed using liquid chromatography-mass spectrometry. GDNPs were extracted and purified using differential ultracentrifugation and sucrose density gradient centrifugation. In vitro models of alcoholic liver injury were established using LO2 cells, whereas C57BL/6 J mice were used as in vivo models. Oxidative stress, inflammation, and liver injury indicators were measured using appropriate kits. Levels of proteins associated with oxidative stress and inflammation were measured via western blot, while nuclear factor erythroid2-related factor 2 (Nrf2) and NF-κB protein expression was tested using immunofluorescence, immunohistochemistry, and flow cytometry. The levels of relevant transcription factors were determined using qPCR. Experimental haematoxylin and eosin staining was used to characterise the liver histological appearance and damage in mice. Network pharmacological analysis of GDNP mRNA sequencing of GDNPs was used to predict drug targets and disease associations using TCMSP. RESULTS: GDNPs primarily included 77 compounds, including organic acids and their derivatives, amino acids and their derivatives, sugars, terpenoids, and flavonoids. GDNPs have features that allow them to be taken up by LO2 cells and promote their proliferation. In vitro data indicated that GDNPs reduced the levels of alcohol-induced reactive oxygen species by activating the Nrf2/HO-1 signalling pathway, whilst inhibiting the NF-κB pathway and thereby reducing NO, tumour necrosis factor-α, and interleukin-1ß levels to alleviate inflammation. An in vivo model showed that GDNPs improved the liver parameters and pathology in mice with alcoholic liver injury. GDNPs activate the Nrf2/HO-1/Keap1 signalling pathway in a p62-dependent manner to exert antioxidant effects. Furthermore, the TLR4/NF-κB signalling pathway was involved in the in vivo anti-inflammatory effect. Network pharmacology also confirmed that the effects of GDNPs on liver disease were associated with oxidative stress and inflammation-related targets and pathways. CONCLUSION: This study showed for the first time that GDNPs can alleviate alcohol-induced liver damage by activating the Nrf2/HO1 signalling pathway and blocking the NF-κB signalling pathway, thus lowering oxidative stress and inflammatory responses. Hereby, we present the Nrf2/HO1 and NF-κB signalling pathways as potential targets and GDNPs as a novel therapeutic approach for the management of alcohol-induced liver damage.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Nanopartículas , Panax , Camundongos , Animais , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Panax/química , Camundongos Endogâmicos C57BL , Inflamação , Estresse Oxidativo , Antioxidantes/farmacologia , Etanol/efeitos adversos , Anti-Inflamatórios/farmacologia , Nanopartículas/química
10.
Ecotoxicol Environ Saf ; 273: 116179, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38460200

RESUMO

It has been shown that exposure to hexavalent Chromium, Cr (Ⅵ), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (Ⅵ) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (Ⅵ) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (Ⅵ) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (Ⅵ) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (Ⅵ) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (Ⅵ) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (Ⅵ) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (Ⅵ), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (Ⅵ).


Assuntos
Barreira Hematoencefálica , NF-kappa B , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , NF-kappa B/metabolismo , Cromo/toxicidade , Gliose , Fator 2 Relacionado a NF-E2/metabolismo , Modelos Animais de Doenças , Hipotálamo/metabolismo
11.
ACS Nano ; 18(11): 7868-7876, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38440979

RESUMO

Diodes based on p-n junctions are fundamental building blocks for numerous circuits, including rectifiers, photovoltaic cells, light-emitting diodes (LEDs), and photodetectors. However, conventional doping techniques to form p- or n-type semiconductors introduce impurities that lead to Coulomb scattering. When it comes to low-dimensional materials, controllable and stable doping is challenging due to the feature of atomic thickness. Here, by selectively depositing dielectric layers of Y2O3 and AlN, direct formation of wafer-scale carbon-nanotube (CNT) diodes are demonstrated with high yield and spatial controllability. It is found that the oxygen interstitials in Y2O3, and the oxygen vacancy together with Al-Al bond in AlN/Y2O3 electrostatically modulate the intrinsic CNTs channel, which leads to p- and n-type conductance, respectively. These CNTs diodes exhibit a high rectification ratio (>104) and gate-tunable rectification behavior. Based on these results, we demonstrate the applicability of the diodes in electrostatic discharge (ESD) protection and photodetection.

12.
Antioxidants (Basel) ; 13(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38539850

RESUMO

In the dynamic field of intensive aquaculture, the strategic application of probiotics has become increasingly crucial, particularly for enhancing resistance to environmental stressors such as ammonia-nitrogen. Over a 42-day period, this study investigated the effects of different probiotic strains-Bacillus subtilis (BS, 6-3-1, and HAINUP40)-on the health and resilience of hybrid groupers. Each strain, distinct in its origin, was assessed for its influence on growth performance, antioxidant capacity, immune gene expressions, and ammonia-nitrogen stress response in the hybrid grouper. The experimental design included a control group and three experimental groups, each supplemented with 1 × 108 CFU/g of the respective probiotic strains, respectively. Our results demonstrated notable differences in growth parameters, including final body weight (FBW) and feed conversion ratio (FCR). The 6-3-1 strain, originating from grouper, exhibited significant improvements in growth, oxidative capacity, and intestinal health. Conversely, the BS strain achieved the highest survival rates under ammonia-nitrogen stress, indicating its superior ability to regulate inflammatory responses despite its less pronounced growth-promoting effects. The HAINUP40 strain was distinguished for its growth enhancement and improvements in intestinal health, though it also showed significant activation of inflammatory genes and decreased resistance to ammonia-nitrogen stress after extended feeding. The uniqueness of this study lies in its detailed examination of the strain-specific effects of probiotics on fish in the context of ammonia-nitrogen stress, a significant challenge in contemporary aquaculture. The research revealed that host-derived probiotics, particularly the 6-3-1 strain, provided more comprehensive benefits for growth performance and stress resilience. In contrast, the BS and HAINUP40 strains exhibited varying efficiencies, with BS excelling in stress resistance and HAINUP40 promoting growth and gut health. In conclusion, this study underscores the complex roles of different probiotic strains in aquaculture, contributing to the understanding of probiotic applications and presenting new approaches to address the challenges of intensive farming.

13.
Biotechnol J ; 19(2): e2300174, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403399

RESUMO

Mesenchymal stem cells (MSCs) and their produced exosomes have demonstrated inherent capabilities of inflammation-guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion-derived MSCs (hMSCs) at a scale of over 1 × 109 cells per batch was reported using a three-dimensional (3D) culture technology based on microcarriers coupled with a spinner bioreactor system. The present study revealed that this large-scale production technology improved the inflammation-guided migration and the inflammatory suppression of hMSCs, without altering their major properties as stem cells. Moreover, these large-scale produced hMSCs showed an efficient treatment against the lipopolysaccharide (LPS)-induced lung inflammation in mice models. Notably, exosomes collected from these large-scale produced hMSCs were observed to inherit the efficient inflammatory suppression capability of hMSCs. The present study showed that 3D culture technology using microcarriers coupled with a spinner bioreactor system can be a promising strategy for the large-scale expansion of hMSCs with improved anti-inflammation capability, as well as their secreted exosomes.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Pneumonia , Humanos , Animais , Camundongos , Células-Tronco , Pneumonia/terapia , Inflamação/terapia
14.
iScience ; 27(3): 109158, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38405614

RESUMO

Polypyrimidine tract-binding protein 3 (PTBP3) plays an important role in the post-transcriptional regulation of gene expression, including mRNA splicing, translation, and stability. Increasing evidence has shown that PTBP3 promotes cancer progression in several tumor types. However, the molecular mechanisms of PTBP3 in renal cell carcinoma (RCC) remain unknown. Here, tissue microarrays (TMAs) suggested that PTBP3 expression was increased in human RCC and that high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. We also showed that PTBP3 binds with HMGA1 mRNA in the 3'UTR region and let-7 miRNAs. PTBP3 interacted with IGF2BP3, and the PTBP3/IGF2BP3 axis prevented let-7 mediated HMGA1 mRNA silencing. PTBP3 promotes renal cancer cell growth and metastasis in vitro and in vivo. Taken together, our findings indicate PTBP3 serves as a regulator of HMGA1 and suggest its potential as a therapeutic agent for RCC.

15.
Neurotoxicology ; 101: 36-45, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311184

RESUMO

Methamphetamine (METH) - induced cognitive impairments may be related to synaptic degeneration at mossy fiber terminals, critical for spatial memory formation in hippocampal circuits. We have previously found METH-induced neurodegeneration in the striatum by increasing the α-synuclein (α-SYN) level. However, whether and how the METH-induced mossy fiber degeneration is also blamed for the abnormal accumulation of α-SYN remains to be elucidated. Chronic METH exposure decreased mossy fiber density but upregulatedα-SYN and phosphorylated TAU (TAU-pSer396) in hippocampal CA3, associated with glial cell overactivation, axonal neuropathies, and memory impairment. Notably, the knockout of the α-SYN gene significantly alleviated the METH-induced mossy fiber degeneration and memory impairment. Meanwhile, the TAU-pSer396 accumulation and glial activation were ameliorated by α-SYN knockout. Our findings suggest an essential role of α-SYN in mediating METH-induced mossy fiber degeneration, providing promising therapeutic and prophylactic targets for METH-related neurodegenerative diseases.


Assuntos
Metanfetamina , Metanfetamina/toxicidade , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Fibras Musgosas Hipocampais/metabolismo , Hipocampo/metabolismo
16.
Inorg Chem ; 63(7): 3436-3443, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38306691

RESUMO

Developing efficient adsorbents for acetylene purification from multicomponent mixtures is of critical significance in the chemical industry, but the trade-off between regenerability and selectivity significantly restricts practical industrial applications. Here, we report ultramicroporous metal-organic frameworks with acetylene-affinity channels to enhance electrostatic interaction between C2H2 and frameworks for the efficient one-step purification of C2H2 from C2H2/CO2/C2H4 mixtures, in which the electrostatic interaction led to high regenerability. The obtained SNNU-277 exhibits significantly higher adsorption capacity for C2H2 than that for both C2H4 and CO2 at 298 K and 0.1 bar, while an ultrahigh selectivity of C2H2/C2H4 (100.6 at 298 K) and C2H2/CO2 (32.8 at 298 K) were achieved at 1 bar. Breakthrough experiments validated that SNNU-277 can efficiently separate C2H2 from C2H2/C2H4/CO2 mixtures. CO2 and C2H4 broke through the adsorption column at 4 and 14.8 min g-1, whereas C2H2 was detected until 177.6 min g-1 at 298 K. Theoretical calculations suggest that the framework is electrostatically compatible with C2H2 and electrostatically repels C2H4 and CO2 in the mixed components. This work highlights the importance of rational pore engineering for maximizing the electrostatic effect with the preferentially absorbed guest molecule for efficient multicomponent separation.

17.
J Inflamm Res ; 17: 1241-1253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415263

RESUMO

Purpose: Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD. Patients and Methods: Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between isatin and neuroinflammation was conducted using BV2 microglial cells. Results: Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably, isatin levels were significantly decreased after anesthesia. Notably, isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia-the pivotal cell type in inflammatory responses. Conclusion: Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.

18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 13-18, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322528

RESUMO

Nanodrugs are widely utilized in the biomedical fields, exhibiting immense potential in cancer therapy in particular. However, tumors exist in an extremely complicated microenvironment where substances like collagen are continuously deposited and remodeled, leading to significant alterations in the mechanical properties of the extracellular matrix (ECM) during tumor development. Previous research has primarily focused on the specific physicochemical properties of nanodrugs, such as particle size, electric charge, shape, surface chemistry, etc., and their effects on cellular uptake, cytotoxicity, and in vivo pharmacokinetics. Limited studies have been done to explore the impact of ECM mechanical properties on nanodrug delivery. In this review, we systematically summarized the relevant research findings on this topic from the perspective of the characteristics and testing methods of tumor ECM mechanics. Additionally, we made a thorough discussion of the potential mechanical and biological mechanisms involved in nanodrug delivery. We proposed several noteworthy research directions. Regarding the overall strategy, there is a need to emphasize targeted delivery that combines ECM mechanics and nanomechanics to achieve precise drug delivery. Regarding the spatial aspect, attention should be given to the nonlinear spatial mechanical heterogeneity within the interior of solid tumors and the construction of mechanic microenvironment-adaptive nanocarriers to improve the delivery efficiency. Regarding the temporal aspect, emphasis should be placed on the dynamic development and changes in the mechanical microenvironment during solid tumor growth and treatment processes. Based on the stromal mechanical characteristics of the tumor tissues of individual patients, personalized treatment strategies can be formulated, which will enhance treatment specificity and efficacy. In addition, issues such as mechanically targeted nanodrug delivery, degradation, and metabolism under dynamic ECM mechanical conditions warrant further investigation.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Microambiente Tumoral
19.
J Nanobiotechnology ; 22(1): 48, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302938

RESUMO

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.


Assuntos
Doenças Inflamatórias Intestinais , Nanopartículas , Panax , Animais , Camundongos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Nanopartículas/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Panax/metabolismo , Receptor 4 Toll-Like/metabolismo
20.
J Cancer Res Clin Oncol ; 150(2): 54, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289495

RESUMO

BACKGROUND/OBJECTIVE: Cervical cancer is the major cause of cancer-related mortalities in women globally. It constitutes one of the life-threatening conditions for women in developing countries. The popularization of cervical cancer screening and the improvement of treatment levels has caused the mortality rate of cervical cancer to decrease gradually, but pelvic floor dysfunction before and after cervical cancer treatment has become prominent and attracted more and more attention. Bibliometric analysis has been carried out in this research. The main goal of this research is to provide a comprehensive insight into the knowledge structure and global research hotspots about pelvic floor dysfunction in cervical cancer. METHODS: Literature related to cervical cancer and pelvic floor dysfunction as of May 2023 was searched on the Web of Science Core Collection (WOSCC). The visualization and bibliometric analyses of the number and contents of publications were performed to analyze the temporal trends, spatial distribution, collaborative networks, influential references, keyword co-occurrence, and clustering. RESULTS: There were 870 publications from 74 countries or regions, with the U.S. publications in a leading position. Since 2020, the number of publications has rapidly increased with the emphasis on the quality of life of cervical cancer patients. Although pelvic floor dysfunction in cervical cancer mainly occurs in developing countries, developed countries have made great contributions to this disease. However, in developing countries such as China and India, the quality of publications needs to be improved. In this field, the studies focused on the sexual dysfunction or urinary incontinence of cervical cancer patients, and the most cited papers discussed the effect of cervical cancer treatment on the sexual activities of females. The frontier keywords were represented by pelvic radiotherapy and risk factors. CONCLUSION: This study provides an objective and comprehensive analysis of the literature available on pelvic floor dysfunction in cervical cancer and identifies future trends and current hotspots. It can provide a valuable reference for researchers in this field.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia , Detecção Precoce de Câncer , Diafragma da Pelve , Qualidade de Vida , China
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