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1.
ACS Nano ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046933

RESUMO

The self-renewal and differentiation properties of cancer stem cells (CSCs) result in chemoresistance in breast cancer. Even though numerous drugs have been developed to target CSCs, they have suffered from inefficient delivery and accumulation at the focal site. Here, a thermoresponsive hydrogel is developed by coencapsulating aggregation-induced emission (AIE)-active photothermal agent and thioridazine (THZ), demonstrating a controllable delivery system triggered by the AIE agent to augment THZ-mediated CSC ablation. Upon near-infrared laser stimuli, the photothermal effect from the AIE agent induces hydrogel deformation for burst drug release. The precise in situ tumor administration of the hydrogel accelerates drug diffusion and accumulation in deep breast cancer lesions. Thus, THZ can invade tumors and provoke massive CSC apoptosis via dopamine receptor blockage and oxidative stress induction. Consequently, effective CSC inhibition and significant suppression of tumor recurrence and metastasis are demonstrated in mice with breast cancer. We believe that this intelligent hydrogel-based delivery system represents a promising treatment strategy for metastatic breast cancer with clinical potential.

2.
Adv Sci (Weinh) ; : e2405575, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39033534

RESUMO

Photothermal therapy (PTT) holds considerable clinical promise. However, insufficient PTT-induced tumor recurrence and metastasis is an urgent practical problem that needs to be solved. Herein, a biomimetic mesoporous organosilicon nano-system called PSAB is designed to precisely deplete cancer stem cells (CSCs) and prevent tumor recurrence and metastasis after PTT. The PSAB system is made up of Aggregation-induced emission (AIE)-active photothermal agent, 2TT-oC26B, and SO2 prodrug, benzothiazole sulfinate (BTS), within mesoporous organosilicon nanoparticles (MON) enclosed by an exterior platelet membrane. PSAB effectively targets CSCs both in vitro and in vivo by P-selectin/CD44 interaction. The degradation of MON and subsequent release of BTS and AIE molecules are facilitated by intracellular glutathione (GSH). Subsequently, the acidic tumor environment triggers the SO2 gas therapy from BTS. This process leads to the depletion of GSH and CSCs elimination. After combining PSAB with photothermal therapy, there is no significant tumor recurrence or metastasis. These results indicate that SO2 gas therapy and AIE-mediated PTT act synergistically to offer a unique approach for preventing tumor recurrence and metastasis after PTT, thus holding significant promise for clinical applications in cancer PTT.

3.
Colloids Surf B Biointerfaces ; 242: 114091, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018913

RESUMO

Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols.

4.
J Agric Food Chem ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833376

RESUMO

This study found that, after microwave treatment at 560 W for 30 s, alkaline protease enzymolysis significantly reduced the allergenicity of ovalbumin (OVA). Furthermore, specific adsorption of allergenic anti-enzyme hydrolyzed peptides in the enzymatic products by immunoglobulin G (IgG) bound to magnetic bead further decreased the allergenicity of OVA. The results indicated that microwave treatment disrupts the structure of OVA, increasing the accessibility of OVA to the alkaline protease. A comparison between 17 IgG-binding epitopes identified through high-performance liquid chromatography-higher energy collisional dissociation-tandem mass spectrometry and previously reported immunoglobulin E (IgE)-binding epitopes revealed a complete overlap in binding epitopes at amino acids (AA)125-135, AA151-158, AA357-366, and AA373-381. Additionally, partial overlap was observed at positions AA41-59, AA243-252, and AA320-340. Consequently, these binding epitopes were likely pivotal in eliciting the allergic reaction to OVA, warranting specific attention in future studies. In conclusion, microwave-assisted enzymolysis synergized with magnetic bead adsorption provides an effective method to reduce the allergenicity of OVA.

6.
Chemotherapy ; : 1-12, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38797169

RESUMO

INTRODUCTION: The aim of the study was to conduct a systematic review to explore the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) for patients with hepatocellular carcinoma (HCC). METHODS: Chinese and English databases (PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and VIP database) were searched from database inception to August 15, 2023. Studies comparing TACE combined with PVE versus TACE alone for patients with HCC were included. The degree of heterogeneity was assessed using I2 statistics and a Q test. The effect size was represented by risk ratio and mean difference (MD), and the effect size range was estimated using a 95% confidence interval (CI). RESULTS: Eight eligible studies were included in the systematic review, involving 689 participants. The results showed that the future liver residual (FLR) of patients treated with TACE combined with PVE was significantly higher than that of those treated with PVE alone (MD = 3.99%; 95% CI: 1.03-6.94). Furthermore, compared with PVE alone, TACE combined with PVE had a positive effect on disease-free survival (odds ratio [OR] = 2.16; 95% CI: 1.20-3.88), recurrence rate (OR = 0.79; 95% CI: 0.07-9.42), and complications (OR = 0.53; 95% CI: 0.30-0.96). There was no statistically significant impact on mortality with TACE combined with PVE treatment. CONCLUSION: The combination of TACE with PVE can significantly reduce the FLR of patients with HCC, with higher disease-free survival, lower recurrence rate, and fewer complications.

7.
J Control Release ; 371: 204-215, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810704

RESUMO

Cuproptosis, a newly discovered mechanism of inducing tumor cell death, primarily relies on the intracellular accumulation of copper ions. The utilization of Cu-based nanomaterials to induce cuproptosis holds promising prospects in future biomedical applications. However, the presence of high levels of glutathione (GSH) within tumor cells hinders the efficacy of cuproptosis. In this study, we have developed a BPTES-loaded biomimetic Cu-doped polypyrrole nanoparticles (CuP) nanosystem (PCB) for enhanced cuproptosis and immune modulation. PCB comprises an internal BPTES and CuP core and an external platelet membrane (PM) that facilitates active targeting to tumor sites following intravenous administration. Subsequently, PCB effectively suppresses glutaminase (GLS1) activity, thereby reducing GSH content. Moreover, CuP catalyze intracellular H2O2, amplifying oxidative stress while simultaneously inducing dihydrolipoyl transacetylase (DLAT) oligomerization through released Cu2+, resulting in cuproptosis. PCB not only inhibits primary tumors but also exhibits inhibitory effects on abscopal tumors. This work represents the first instance where GLS inhibition has been employed to enhance cuproptosis and immunotherapy. It also provides valuable insights into further investigations on cuproptosis.


Assuntos
Materiais Biomiméticos , Neoplasias da Mama , Cobre , Glutamina , Imunoterapia , Nanopartículas , Polímeros , Pirróis , Cobre/química , Polímeros/química , Nanopartículas/química , Nanopartículas/administração & dosagem , Animais , Feminino , Pirróis/administração & dosagem , Pirróis/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Imunoterapia/métodos , Linhagem Celular Tumoral , Glutamina/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/administração & dosagem , Camundongos Endogâmicos BALB C , Glutaminase/metabolismo , Glutaminase/antagonistas & inibidores , Camundongos , Glutationa/metabolismo
8.
Angew Chem Int Ed Engl ; 63(29): e202404314, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38712987

RESUMO

Atomically precise low-nuclearity (n<10) silver nanoclusters (AgNCs) have garnered significant interest due to their size-dependent optical properties and diverse applications. However, their synthesis has remained challenging, primarily due to their inherent instability. The present study introduces a new feasible approach for clustering silver ions utilizing highly negative and redox-inert polyoxoniobates (PONbs) as all-inorganic ligands. This strategy not only enables the creation of novel Ag-PONb composite nanoclusters but also facilitates the synthesis of stable low-nuclearity AgNCs. Using this method, we have successfully synthesized a small octanuclear rhombic [Ag8]6+ AgNC stabilized by six highly negative [LiNb27O75]14- polyoxoanions. This marks the first PONb-protected superatomic AgNC, designated as {Ag8@(LiNb27O75)6} (Ag8@Nb162), with an aesthetically spherical core-shell structure. The crystalline Ag8@Nb162 is stable under ambient conditions, What's more, it is water-soluble and able to maintain its molecular cluster structure intact in water. Further, the stable small [Ag8]6+ AgNC has interesting temperature- and pH-dependent reversible fluorescence response, based on which a multiple optical encryption mode for anti-counterfeit technology was demonstrated. This work offers a promising avenue for the synthesis of fascinating and stable PONb-protected AgNCs and sheds light on the development of new-type optical functional materials.

9.
Inorg Chem ; 63(20): 9204-9211, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38701353

RESUMO

In this work, a novel organodiphosphate-containing inorganic-organic hybrid polyoxoniobate (PONb) ring {(PO3CH2CH2PO3H)4Nb8O16}4- (Nb8P8) has been achieved by a one-pot hydrothermal method. The ring is constructed from a tetragonal {Nb8O36} motif and four {PO3CH2CH2PO3H} ligands. Interestingly, Nb8P8 can be joined together via K-H2O clusters {K2(H2O)4(OH)2} to form one-dimensional chains {[K2(H2O)4(OH)2]Nb8P8}n and further linked by {Cu(en)2}2+ (en = ethylenediamine) complexes, resulting in a three-dimensional supramolecular framework {[Cu(en)2]2[K2(H2O)4(OH)2]Nb8P8}·3en·H2O (1). 1 exhibits good chemical and thermal stability and has a high water vapor adsorption capacity of ≤224 cm3 g-1 (22.71 mol·mol-1) at 298 K, outperforming most of the known polyoxometalate-based materials. Impedance measurements prove that 1 can transfer protons with moderate conductivity. This study not only contributes to the structural diversity of organodiphosphate-containing PONbs and PONb rings but also provides a reference for the development of PONb-based materials with unique performance.

10.
Molecules ; 28(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38138594

RESUMO

In this paper, a low-temperature thick oil demulsifier with high polarity was prepared by introducing ethylene oxide, propylene oxide block, and butylene oxide using m-diphenol as a starting agent. The main reasons for the difficulty involved in the low-temperature emulsification of extractive fluids were explained by analyzing the synthetic influencing factors and infrared spectra of the star comb polymer (PR-D2) and by analyzing the four fractions, interfacial energies, and zeta potentials of crude oils from the Chun and Gao fields. The effects of PR-D2 surfactant on the emulsification performance of crude oil recovery fluids were investigated via indoor and field experiments. The experimental results indicate that the optimal synthesis conditions for this emulsion breaker are as follows: a quality ratio of ionic reaction intermediates and meso-diphenol of R = 10:1; 1 g of the initiator; a polymerization temperature of 80 °C; and a reaction time of 8 h. Colloidal asphaltenes in the crude oil were the main factor hindering the low-temperature demulsification of the Gao oilfield's extractive fluids, and the reason for the demulsification difficulty of the extractive fluids in the Chun oilfield is that the temperature of demulsification is lower than the wax precipitation point. The demulsification rate of the Chun oilfield's extractive fluids reached more than 98% when the PR-D2 concentration reached 150 mg/L at 43 °C. The demulsification rate of the Gao oilfield's extractive fluids reached more than 98% at a PR-D2 concentration of 150 mg/L at 65 °C. The field experiments show that the Chun oilfield's extractive fluids can still demulsify after the temperature is reduced to 43 °C in winter. The emulsification temperature of the Gao oilfield's extractive fluids was reduced from 73 °C to 68 °C, with an excellent demulsification effect.

11.
Angew Chem Int Ed Engl ; 62(46): e202312706, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37793987

RESUMO

Inspired by the metal-oxo cluster structural feature and charge separation behaviour of the oxygen evolving center (OEC) in photosystem II (PS-II) under photoirradiation, a new crystalline photochromic polyoxomolybdate, MV2 [ß-Mo8 O26 ] (1, MV=methyl viologen cation), is designed as a biomimetic oxygen evolution reaction (OER) catalyst in neutral electrolytes. After photoinduced electron transfer (PIET) with colour change from colourless to grey, it remains in an ultra-stable charge-separated state over a year under ambient conditions. The observed overpotential at 10 mA ⋅ cm-2 and Tafel slope decrease by 49 mV and 62.8 mV ⋅ dec-1 after coloration, respectively. The outstanding OER performance of the coloured state in neutral electrolytes even outperforms the commercial RuO2 benchmark. Experimental and theoretical studies show that oxygen holes within polyanions after irradiation serve as sites for enhancing direct O-O coupling, thus effectively promoting OER. This is the first successful application of electron-transfer photochromism to realize OER activity gain.

12.
Cureus ; 15(8): e43365, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37700966

RESUMO

Small bowel obstruction is a frequently encountered surgical condition in adults. Its most prevalent causes include adhesions resulting from prior abdominal surgery or peritoneal infection. However, cases of small bowel obstruction caused by omental bands in elderly individuals with no prior abdominal surgeries are exceedingly rare, with only a few reported in the literature. Here, we report a case of an elderly patient with small bowel obstruction caused by internal herniation through an omental band, without prior abdominal surgery or trauma. The initial impression was mesenteric ischemia, which posed a diagnostic dilemma as the patient did not exhibit any clinical risk factors for mesenteric ischemia with absent history of previous trauma or abdominal surgery. A computed tomography (CT) scan was performed, revealing clustering of small bowel loops in the right hemiabdomen with mild dilatation and a close loop configuration indicative of an internal hernia. Internal hernias are rare and challenging to diagnose clinically as they lack specific signs and symptoms. In this case, CT played a crucial role in enabling preoperative diagnosis of an internal hernia and guiding early management.

13.
Inorg Chem ; 62(26): 10044-10048, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37338532

RESUMO

A unique heteropolyoxotantalate (hetero-POTa) cluster [P2O7Ta5O14]7- (P2Ta5) was first developed using pyrophosphate as a key to open the ultrastable skeleton of the classical Lindqvist-type [Ta6O19]8- precursor. The P2Ta5 cluster can serve as a general and flexible secondary building unit to create a family of brand-new multidimensional POTa architectures. This work not only promotes the limited structural diversity of hetero-POTa but also provides a practical strategy for new extended POTa architectures.

14.
Nanomaterials (Basel) ; 13(10)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37242033

RESUMO

The high porosity of a GaN porous structure (PS) makes it mechanically semi-flexible and can shield against the stress from the thick growth template on an overgrown layer to control the lattice structure or composition within the overgrown layer. To understand this stress shield effect, we investigated the lattice constant variations among different growth layers in various samples of overgrown Al0.3Ga0.7N on GaN templates under different strain-relaxation conditions based on d-spacing crystal lattice analysis. The fabrication of a strain-damping PS in a GaN template shields against the stress from the thick GaN template on the GaN interlayer, which lies between the PS and the overgrown AlGaN layer, such that the stress counteraction of the AlGaN layer against the GaN interlayer can reduce the tensile strain in AlGaN and increase its critical thickness. If the GaN interlayer is thin, such that a strong AlGaN counteraction occurs, the increased critical thickness can become larger than the overgrown AlGaN thickness. In this situation, crack-free, thick AlGaN overgrowth is feasible.

15.
World J Surg Oncol ; 21(1): 100, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941629

RESUMO

OBJECTIVE: To construct a predictive model for pain in patients undergoing hepatic arterial chemoembolization (TACE) in interventional operating room. METHODS: Through literature review and expert interviews, a questionnaire was prepared for the assessment of pain factors in patients with hepatic arterial chemoembolization. A prospective cohort study was used to select 228 patients with hepatic arterial chemoembolization in a tertiary and first-class hospital. The data of the patients in the pain group and the non-pain group were compared, and a rapid screening prediction model was constructed by univariate analysis and logistic regression analysis, and its prediction effect was tested. RESULTS: Tumor size, liver cancer stage, and chemoembolization with drug-loaded microspheres and pirarubicin hydrochloride (THP) mixed with lipiodol were independent predictors of pain in patients after hepatic arterial chemoembolization. Finally, the pain prediction model after TACE was obtained. The results of Hosmer-Lemeshow test showed that the model fit was good (χ2 = 13.540, p = 0.095). The area under the receiver operating characteristic curve was 0.798, p < 0.001. CONCLUSION: The rapid screening and prediction model of pain in patients undergoing hepatic arterial chemoembolization has certain efficacy, which is helpful for clinical screening of patients with high risk of pain, and can provide reference for predictive pain management decision-making.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/patologia , Resultado do Tratamento
16.
Ann Gastroenterol Surg ; 7(1): 10-26, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36643355

RESUMO

Crohn's disease (CD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. With the increased availability of modalities in the last two decades, the treatment of CD has advanced remarkably. Although medical treatment is the mainstay of therapy, most patients require surgery during the course of their illness, especially those who experience complications. Nutritional optimization and ERAS implementation are crucial for patients with CD who require surgical intervention to reduce postoperative complications. The increased surgical risk was found to be associated with the use of corticosteroids, but the association of surgical risk with immunomodulators, biologic therapy, such as anti-TNF mediations, anti-integrin medications, and anti-IL 12/23 was low in certainty. Decisions about preoperative medication must be made on an individual case-dependent basis. Preoperative imaging studies can assist in the planning of appropriate surgical strategies and approaches. However, patients must be informed of any alterations to their treatment. In summary, the management of perioperative medications and surgery-related decision-making should be individualized and patient-centered based on a multidisciplinary approach.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970618

RESUMO

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.


Assuntos
Extratos Vegetais/farmacologia , Asteraceae , Triterpenos , Sesquiterpenos/farmacologia , Anti-Inflamatórios , Compostos Fitoquímicos/farmacologia
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-971270

RESUMO

OBJECTIVE@#To describe the submucosal microbial profiles of peri-implantitis and healthy implants, and to explore bacteria that might be correlated with clinical parameters.@*METHODS@#In the present cross-sectional study, 49 patients were recruited. Each patient contributed with one implant, submucosal biofilms were collected from 20 healthy implants and 29 implants with peri-implantitis. DNA was extracted and bacterial 16S ribosomal RNA (16S rRNA) genes were amplified. Submucosal biofilms were analyzed using 16S rRNA sequencing at Illumina MiSeq platform. Differences between the groups were determined by analyzing α diversity, microbial component and microbial structure. The potential correlation between the bacteria with pocket probing depth (PPD) of peri-implant calculated by Spearman correlation analysis.@*RESULTS@#The α diversity of submucosal microbial of health group was significantly lower than that in peri-implantitis group (Chao1 index: 236.85±66.13 vs. 150.54±57.43, P < 0.001; Shannon index: 3.42±0.48 vs. 3.02±0.65, P=0.032). Principal coordinated analysis showed that the submucosal microbial structure had significant difference between healthy and peri-implantitis groups [R2=0.243, P=0.001, analysis of similarities (ANOSIM)]. Compared with healthy implants, relative abundance of periodontal pathogens were higher in peri-implantitis, including members of the red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and some members of orange complex (Precotella intermedia, Eubacterium nodatum, Parvimonas micra), as well as some new periodontal pathogens, such as Fillifactor alocis, Fretibacterium fastidiosum, Desulfobulbus sp._HMT_041, and Porphyromonas endodontalis. Spearman correlation analysis revealed that the relative abundance of Treponema denticola (r=0.686, P < 0.001), Tannerella forsythia (r=0.675, P < 0.001), Fretibacterium sp. (r=0.671, P < 0.001), Desulfobulbus sp._HMT_041 (r=0.664, P < 0.001), Filifactor alocis (r=0.642, P < 0.001), Fretibacterium fastidiosum (r=0.604, P < 0.001), Porphyromonas gingivalis (r=0.597, P < 0.001), Porphyromonas endodontalis (r=0.573, P < 0.001) were positive correlated with PPD. While the relative abundance of Rothia aeria (r=-0.615, P < 0.001) showed negatively correlation with PPD.@*CONCLUSION@#Marked differences were observed in the microbial profiles of healthy implants and peri-implantitis. The members of red and orange complex as well as some new periodontal pathogens seem to play an important role in peri-implant disease. Compared with healthy implants, the submucosal microbial of peri-implantitis were characterized by high species richness and diversity.


Assuntos
Humanos , Peri-Implantite/microbiologia , Estudos Transversais , RNA Ribossômico 16S/genética , Carga Bacteriana , Porphyromonas gingivalis , Implantes Dentários
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-976533

RESUMO

Objective To construct the auxiliary system of outpatient drug distribution, reduce errors and improve the quality of outpatient pharmaceutical service. Methods The bar code technology was used to independently develop outpatient pharmacy dispensing assistant system. The system design and function are introduced. The practical application effect of the system was evaluated on dispensing errors, efficiency and pharmacist evaluation. Results Based on the special network environment of the hospital, the system integrated the functions of drug check, prescription right management, expiration date management and medication instruction. After using the system, the number of dispensing errors decreased from 84 to 25. The waiting time for patients to receive medicine decreased by 151 seconds. All pharmacists surveyed agreed that auxiliary system was helpful to pharmacists’ work. Conclusion The system reduced the medication dispensing error in outpatient pharmacy, improved work efficiency and the quality of pharmaceutical care.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1008847

RESUMO

This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.


Assuntos
Camundongos , Animais , Pós , Receptores Tipo I de Fatores de Necrose Tumoral , Ácido Glutâmico , Fator de Necrose Tumoral alfa/metabolismo , Galactose/efeitos adversos , Modelos Animais de Doenças , Disfunção Cognitiva/prevenção & controle , Quimiocinas , Medicamentos de Ervas Chinesas
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