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2.
Int J Biol Macromol ; 260(Pt 2): 129353, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242386

RESUMO

Infection and chronic inflammation caused by oxidative stress are major challenges in chronic wound healing. Preparing a simple, efficient hydrogel with reactive oxygen-scavenging properties for chronic wound repair is a promising strategy. Herein, we report an injectable, self-repairing hydrogel with antioxidant and antibacterial properties that can be used to regenerate diabetic wounds. Hydrogels are prepared by coordination crosslinking of gelatin (Gel), a natural biopolymer derived from collagen, with Zr4+. Because of the dynamic properties of metal ion coordination bonds and the bactericidal effect of Zr4+, the obtained coordination hydrogels exhibit self-healing, injectable, and antibacterial properties. The plant polyphenol "proanthocyanidins," which has reactive oxygen-scavenging and anti-inflammatory effects, was simultaneously loaded into the coordination hydrogel during cross-linking. We obtained a versatile hydrogel that is easy to prepare, resistant to mechanical irritation, and antioxidant, and antibacterial in vitro. We further demonstrated that the injectable self-healing hydrogels could effectively repair diabetic skin wounds and accelerate collagen deposition and wound healing. This study shows that the multifunctional antioxidant hydrogel has great potential in developing multifunctional biomaterials for chronic wound healing.


Assuntos
Diabetes Mellitus , Proantocianidinas , Prunella , Hidrogéis/farmacologia , Antioxidantes/farmacologia , Zircônio , Aceleração , Antibacterianos/farmacologia , Oxigênio , Colágeno
3.
Crit Rev Oncol Hematol ; 193: 104205, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036153

RESUMO

Glioblastoma is a fatal intracranial tumor with a poor prognosis, exhibiting uninterrupted malignant progression, widespread invasion throughout the brain leading to the destruction of normal brain tissue and inevitable death. Monoclonal antibodies alone or conjugated with cytotoxic payloads to treat patients with different solid tumors showed effective. This treatment strategy is being explored for patients with glioblastoma (GBM) to obtain meaningful clinical responses and offer new drug options for the treatment of this devastating disease. In this review, we summarize clinical data (from pubmed.gov database and clinicaltrial.gov database) on the efficacy and toxicity of naked antibodies and antibody-drug conjugates (ADCs) against multiple targets on GBM, elucidate the mechanisms that ADCs act at the site of GBM lesions. Finally, we discuss the potential strategies for ADC therapies currently used to treat GBM patients.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Imunoconjugados , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Imunoconjugados/uso terapêutico
4.
Surg Endosc ; 38(3): 1592-1599, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38148405

RESUMO

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.


Assuntos
Robótica , Cirurgiões , Telemedicina , Humanos , Robótica/métodos , Estudos de Viabilidade , Telemedicina/métodos
5.
Proc Natl Acad Sci U S A ; 120(51): e2300681120, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38100419

RESUMO

Idiopathic normal pressure hydrocephalus (iNPH) is an enigmatic neurological disorder that develops after age 60 and is characterized by gait difficulty, dementia, and incontinence. Recently, we reported that heterozygous CWH43 deletions may cause iNPH. Here, we identify mutations affecting nine additional genes (AK9, RXFP2, PRKD1, HAVCR1, OTOG, MYO7A, NOTCH1, SPG11, and MYH13) that are statistically enriched among iNPH patients. The encoded proteins are all highly expressed in choroid plexus and ependymal cells, and most have been associated with cilia. Damaging mutations in AK9, which encodes an adenylate kinase, were detected in 9.6% of iNPH patients. Mice homozygous for an iNPH-associated AK9 mutation displayed normal cilia structure and number, but decreased cilia motility and beat frequency, communicating hydrocephalus, and balance impairment. AK9+/- mice displayed normal brain development and behavior until early adulthood, but subsequently developed communicating hydrocephalus. Together, our findings suggest that heterozygous mutations that impair ventricular epithelial function may contribute to iNPH.


Assuntos
Hidrocefalia de Pressão Normal , Hidrocefalia , Humanos , Camundongos , Animais , Adulto , Pessoa de Meia-Idade , Hidrocefalia de Pressão Normal/genética , Hidrocefalia de Pressão Normal/complicações , Hidrocefalia/genética , Encéfalo , Plexo Corióideo , Mutação , Proteínas
6.
Sci Rep ; 13(1): 17751, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853050

RESUMO

Underground mining activities can easily trigger surface subsidence and cause damage to surface soil. However, there is still a lack of studies on damaged soil, restricting ecological remediation in mining-induced subsidence regions to a certain degree. Focusing on the particular example of No. 4 Mine in Yili, Xinjiang, China, this study comprehensively combined field sampling, laboratory experiments, and data analysis to investigate the variation rules of basic physical properties and shear characteristics of soil samples. The latter had different subsidence degrees (0, 0-20, 20-40, and above 40 cm) and various depths (0- 10, 10-20, 20- 40, 40-60, and 60-80 cm). The experimental results show that: First, the natural density and dry unit weight of shallow soil in the serious-subsidence region were more significantly affected by mining-induced subsidence than the conditions in the deep layer, which also dropped with the increase in subsidence degree (with a mean drop rate of 7%). Second, serious subsidence could greatly counteract the positive effect of slight and moderate subsidence on the soil shear strength, with a drop rate of up to 30.7%. Third, compared with soil physical indices, mining-induced subsidence more easily affected shear strength indices. In particular, the soil samples taken from 0 to 10 cm depth in the slight subsidence area and 60-80 cm depth in the moderate subsidence area were most significantly affected by mining-induced subsidence, with PCA comprehensive scores of over 1.5. The present study can con-tribute to gaining in-depth knowledge of the damage characteristics of surface soil under mining-induced subsidence and provide a theoretical foundation for formulating reasonable coal mining strategies and ecological protection measures.

7.
Phytother Res ; 37(12): 5639-5656, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37690821

RESUMO

Hypericin can be derived from St. John's wort, which is widely spread around the world. As a natural product, it has been put into clinical practice such as wound healing and depression for a long time. In this article, we review the pharmacology, pharmacokinetics, and safety of hypericin, aiming to introduce the research advances and provide a full evaluation of it. Turns out hypericin, as a natural photosensitizer, exhibits an excellent capacity for anticancer, neuroprotection, and elimination of microorganisms, especially when activated by light, potent anticancer and antimicrobial effects are obtained after photodynamic therapy. The mechanisms of its therapeutic effects involve the induction of cell death, inhibition of cell cycle progression, inhibition of the reuptake of amines, and inhibition of virus replication. The pharmacokinetics properties indicate that hypericin has poor water solubility and bioavailability. The distribution and excretion are fast, and it is metabolized in bile. The toxicity of hypericin is rarely reported and the conventional use of it rarely causes adverse effects except for photosensitization. Therefore, we may conclude that hypericin can be used safely and effectively against a variety of diseases. We hope to provide researchers with detailed guidance and enlighten the development of it.


Assuntos
Hypericum , Perileno , Perileno/farmacologia , Antracenos , Morte Celular , Fármacos Fotossensibilizantes/farmacologia
8.
iScience ; 26(8): 107333, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37529106

RESUMO

Globally, stroke is one of the leading causes of death and significant contributors to disability. Gaining a thorough comprehension of the underlying pathogenic processes is essential for stroke treatment and prevention. In this study, we investigated the role of p21-activated kinase 1 (PAK1) in stroke by using oxygen-glucose deprivation (OGD) and transient middle cerebral artery occlusion and reperfusion (tMCAO/R) models. We reported that focal ischemia and reperfusion affect the PAK1 expression and activity levels. We further demonstrated that PAK1 is responsible for the endothelial hyperpermeability that occurs in the early stages of ischemia and reperfusion. Additionally, inhibition of PAK1 was discovered to alleviate blood-brain barrier disruption and protect against brain injury induced by tMCAO/R. Mechanistically, we provide the evidence that PAK1 regulates the formation of stress fibers and expression of surface junctional proteins. Together, our findings reveal a pathogenic function of PAK1 in stroke.

9.
J Mater Chem B ; 11(32): 7582-7608, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37522237

RESUMO

Glucose oxidase (GOx) has attracted a lot of attention in the field of diabetes diagnosis and treatment in recent years owing to its inherent biocompatibility and glucose-specific catalysis. GOx can effectively catalyze the oxidation of glucose in the blood to hydrogen peroxide (H2O2) and glucuronic acid and can be used as a sensitive element in biosensors to detect blood glucose concentrations. Nanomaterials based on the immobilization of GOx can significantly improve the performance of glucose sensors through, for example, reduced electron tunneling distance. Moreover, various insulin-loaded nanomaterials (e.g., metal-organic backbones, and mesoporous silica nanoparticles) have been developed for the control of blood glucose concentrations based on GOx catalytic chemistry. These nano-delivery carriers are capable of releasing insulin in response to GOx-mediated changes in the microenvironment, allowing for a rapid return of the blood microenvironment to a normal state. Therefore, glucose biosensors and insulin delivery vehicles immobilized with GOx are important tools for the diagnosis and treatment of diabetes. This paper reviews the characteristics of various GOx-based nanomaterials developed for glucose biosensing and insulin-responsive release as well as research progress, and also highlights the current challenges and opportunities facing this field.


Assuntos
Diabetes Mellitus , Nanocompostos , Humanos , Glicemia , Glucose Oxidase , Peróxido de Hidrogênio , Glucose , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Insulina , Insulina Regular Humana
10.
Toxics ; 11(7)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37505570

RESUMO

The stability of drinking water distribution systems and the management of disinfection by-products are critical to ensuring public health safety. In this paper, the interrelationships between corrosion products in the network, microbes, and drinking water quality are elucidated. This review also discusses the mechanisms through which corrosive by-products from the piping network influence the decay of disinfectants and the formation of harmful disinfection by-products. Factors such as copper corrosion by-products, CuO, Cu2O, and Cu2+ play a significant role in accelerating disinfectant decay and catalyzing the production of by-products. Biofilms on pipe walls react with residual chlorine, leading to the formation of disinfection by-products (DBPs) that also amplify health risks. Finally, this paper finally highlights the potential of peroxymonosulfate (PMS), an industrial oxidant, as a disinfectant that can reduce DBP formation, while acknowledging the risks associated with its corrosive nature. Overall, the impact of the corrosive by-products of pipe scale and microbial communities on water quality in pipe networks is discussed, and recommendations for removing DBPs are presented.

11.
iScience ; 26(6): 106956, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37378311

RESUMO

Pressure injuries (PIs) are localized tissue damage resulting from prolonged compression or shear forces on the skin or underlying tissue, or both. Different stages of PIs share common features include intense oxidative stress, abnormal inflammatory response, cell death, and subdued tissue remodeling. Despite various clinical interventions, stage 1 or stage 2 PIs are hard to monitor for the changes of skin or identify from other disease, whereas stage 3 or stage 4 PIs are challenging to heal, painful, expensive to manage, and have a negative impact on quality of life. Here, we review the underlying pathogenesis and the current advances of biochemicals in PIs. We first discuss the crucial events involved in the pathogenesis of PIs and key biochemical pathways lead to wound delay. Then, we examine the recent progress of biomaterials-assisted wound prevention and healing and their prospects.

12.
Ecotoxicol Environ Saf ; 262: 115178, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37356399

RESUMO

The contamination of surface waters in China with Per- and polyfluoroalkyl (PFASs) has been extensively studied in recent decades, however, almost all studies have been conducted in small areas and/or limited samples, which are not representative of the nationwide contamination of surface water environments with PFASs. In this study, attempt was made to provide a comprehensive report about PFASs pollution in Chinese surface water based on the PRISMA. By analyzing 111 papers published between 2006 and 2022, we provide a systematic review of the pollution of PFASs in surface water environments in China. The results show that 26 PFASs contaminants were detected at least once in China's surface water environment and were mainly concentrated in the eastern part of China. Most surface water environments in China had mean PFASs concentrations below 100 ng/L. The most polluted place was the Xiaoqing River, where sampling results in 2020 showed PFASs concentrations as high as 25,429 ng/L, followed by the Tangxun Lake, the Xi River, the Daling River, the Majia River, the Baiyangdian Lake, the Liuxi River, the Jiaolai River, the Tuo River and the Zhimai River. The Xiaoqing River also has the highest concentration of the novel pollutant, with concentrations of HFPO-TA and HFPO-DA as high as 1039 ng/L and 164 ng/L. Based on the source analysis, fluoropolymer manufacturing plants are the main source of PFASs pollutants in surface water. The results of the base risk analysis using risk quotients value (RQ) method show that the RQ values of the Xiaoqing River, the surface water near Bohai Bay, the Majia River and the Tuo River PFOA are 36.9, 7.7, 3.6 and 2.1 respectively, which are high risk areas and require enhanced control. This study provides information on surface waters contaminated by PFASs nationwide, and the results can be used as a reference for the development of pollution control and management strategies for PFASs in surface waters in China.

13.
Phytomedicine ; 113: 154721, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36870824

RESUMO

BACKGROUND: Liver fibrosis (LF) is a trauma repair process carried out by the liver in response to various acute and chronic liver injuries. Its primary pathological characteristics are excessive proliferation and improper dismissal of the extracellular matrix, and if left untreated, it will progress into cirrhosis, liver cancer, and other diseases. Hepatic stellate cells (HSCs) activation is intimately associated to the onset of LF, and it is anticipated that addressing HSCs proliferation can reverse LF. Plant-based small-molecule medications have anti-LF properties, and their mechanisms of action involve suppression of extracellular matrix abnormally accumulating as well as anti-inflammation and anti-oxidative stress. New targeting HSC agents will therefore be needed to provide a potential curative response. PURPOSE: The most recent HSC routes and small molecule natural plants that target HSC described domestically and internationally in recent years were examined in this review. METHODS: The data was looked up using resources including ScienceDirect, CNKI, Web of Science, and PubMed. Keyword searches for information on hepatic stellate cells included "liver fibrosis", "natural plant", "hepatic stellate cells", "adverse reaction", "toxicity", etc. RESULTS: We discovered that plant monomers can target and control various pathways to prevent the activation and proliferation of HSC and promote the apoptosis of HSC in order to achieve the anti-LF effect in this work by compiling the plant monomers that influence many common pathways of HSC in recent years. It demonstrates the wide-ranging potential of plant monomers targeting different routes to combat LF, with a view to supplying new concepts and new strategies for natural plant therapy of LF as well as research and development of novel pharmaceuticals. The investigation of kaempferol, physalin B, and other plant monomers additionally motivated researchers to focus on the structure-activity link between the main chemicals and LF. CONCLUSION: The creation of novel pharmaceuticals can benefit greatly from the use of natural components. They are often harmless for people, non-target creatures, and the environment because they are found in nature, and they can be employed as the starting chemicals for the creation of novel medications. Natural plants are valuable resources for creating new medications with fresh action targets because they feature original and distinctive action mechanisms.


Assuntos
Cirrose Hepática , Hepatopatias , Humanos , Cirrose Hepática/metabolismo , Fibrose , Preparações Farmacêuticas
14.
Toxics ; 11(3)2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36976982

RESUMO

Laboratory experiments were carried out to analyze 39 soil samples collected from four industrial areas in Xuzhou City using inductively coupled plasma mass spectrometry and atomic fluorescence spectrometry. The descriptive statistics of heavy metals (HMs) in the soil profiles showed that the HM content at three depths was highly variable, and most coefficients of variation (CVs) showed moderate variability. The enrichment of Cd at all depths exceeded the risk screening value, and Cd pollution occurred in four plants. The enrichment of the other HMs at three depths was mainly concentrated in the pharmaceutical plant A and chemical plant C. It was found that the different HMs had different vertical distribution characteristics. For the different industrial plants, the raw materials and products not only made the spatial distribution characteristics of the HMs different, but also caused the HM types and contents to differ. The average single pollution indices of Cd in plant A, iron-steel plant B, and plant C indicated a slight pollution level. The other seven HMs in A, B, and C and all HMs in chemical plant D belonged to the safe category. The mean values of the Nemerow pollution index in the four industrial plants belonged to the warning category. The analysis showed that none of the HMs posed potential noncarcinogenic health risks, and only the carcinogenic health risks of Cr in plants A and C were unacceptable. The carcinogenic effect of Cr through the inhalation intake of resuspended soil particulates and that of Cd, Ni, and As via direct oral ingestion were the main exposure pathways.

15.
Cell Biol Toxicol ; 39(4): 1341-1358, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36449143

RESUMO

Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. Herein, the current study was intended to ascertain the function of miR-488 and its modulatory mechanism in GC. Initially, human GC cells were assayed for their in vitro malignancy after miRNA gain- or loss-of-function and RNA interference or overexpression. Also, tumorigenesis and liver metastasis were evaluated in nude mouse models. Results demonstrated that miR-488 elevation suppressed GC (MKN-45 and OCUM-1) cell proliferation, migration, and invasiveness in vitro and reduced their tumorigenesis and liver metastasis in vivo. The luciferase assay identified that miR-488 bound to HULC and inhibited its expression. Furthermore, HULC could enhance EZH2-H3K27me3 enrichment at the p53 promoter region and epigenetically repress the p53 expression based on the data from RIP- and ChIP-qPCR assay. Additionally, HULC was validated to enhance GC growth and metastasis in vitro and in vivo. Overall, HULC re-expression elicited by miR-488 inhibition can enhance EZH2-H3K27me3 enrichment in the p53 promoter and repress the p53 expression, thus promoting the growth and metastasis of GC.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Humanos , Camundongos , Carcinogênese , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas , Neoplasias Hepáticas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Proteína Supressora de Tumor p53/genética
16.
Macromol Rapid Commun ; 44(3): e2200674, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36205697

RESUMO

Hydrogels are 3D network structures composed of physically or chemically crosslinked, hydrophilic molecules. Compared with conventional hydrogels with static and permanent network structures, injectable and responsive hydrogels generated from dynamic networks, have attracted increasing attention from various disciplines due to their wide-ranging applications in tissue engineering, drug delivery, soft robotics, etc. Herein, an injectable self-healing and multiple-responsive hyaluronic acid (HA)- histamine (His)/metal hydrogel is developed by modifying His onto HA and the subsequent, dynamic coordination between imidazole and metal ions. The pH-responsive and mechanical behaviors exhibited by the HA-His/metal hydrogels are tunable with the kinds and the concentrations of metal ions. The HA-His/Zr4+ hydrogels demonstrate a moldable capability at a neutral pH and a multi-stimulus-responsive capability when exposed to a weak alkaline environment and hyaluronidase, which inhibits bacterial growth and biofilm formation. Biocompatibilities and accelerated wound healing are demonstrated in vitro and in vivo and are thoroughly investigated and well characterized. The HA-His/Zr4+ hydrogel has great potential in various biomedical applications, such as pH- and hyaluronidase-responsive sustained release, antibacterial, and implantable materials for tissue engineering.


Assuntos
Ácido Hialurônico , Hidrogéis , Hidrogéis/química , Ácido Hialurônico/química , Histamina , Engenharia Tecidual , Hialuronoglucosaminidase , Antibacterianos/química
18.
Front Oncol ; 12: 898640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387114

RESUMO

Background: Endoscopic submucosal dissection (ESD) has been accepted as the standard treatment for the appropriate indication of early gastric cancer (EGC). Determining the risk of lymph node metastasis (LNM) is critical for the following treatment selection after ESD. This study aimed to develop a predictive model to quantify the probability of LNM in EGC to help minimize the invasive procedures. Methods: A total of 952 patients with EGC who underwent radical gastrectomy were retrospectively reviewed. LASSO regression was used to help screen the potential risk factors. Multivariate logistic regression was used to establish a predictive nomogram, which was subjected to discrimination and calibration evaluation, bootstrapping internal validation, and decision curve analysis. Results: Results of multivariate analyses revealed that gender, fecal occult blood test, CEA, CA19-9, histologic differentiation grade, lymphovascular invasion, depth of infiltration, and Ki67 labeling index were independent prognostic factors for LNM. The nomogram had good discriminatory performance, with a concordance index of 0.816 (95% CI 0.781-0.853). The validation dataset yielded a corrected concordance index of 0.805 (95% CI 0.770-0.842). High agreements between ideal curves and calibration curves were observed. Conclusions: The nomogram is clinically useful for predicting LNM after ESD in EGC, which is beneficial to identifying patients who are at low risk for LNM and would benefit from avoiding an unnecessary gastrectomy.

19.
Int J Nanomedicine ; 17: 2493-2502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669001

RESUMO

Introduction: Gastric cancer remains a major clinical issue and little progress has been made in the treatment of gastric cancer patients during recent decades. Nanoparticles provide a versatile platform for the diagnosis and treatment of gastric cancer. Methods: We prepared 7-ethyl-10-hydroxycamptothecin (SN-38) 125I-radiolabelled biodegradable nanoparticles with folate surface modification (125I-SN-38-FA-NPs) as a novel nanoplatform for targeted gastric carcinoma theranostics. We characterized this system in terms of particle size, morphology, radiostability, and release properties and examined the in vitro cytotoxicity and cellular uptake properties of 125I-SN-38-FA-NPs in MNK 7 and NCI-N7 cells. The pharmacokinetics and biodistribution of 125I-SN-38-FA-NPs were imaged by single photon emission computer tomography (SPECT). An MNK7 tumor-bearing model were established and the in vivo antitumor activity of 125I-SN-38-FA-NPs was evaluated. Results: SN-38 was readily radiolabeled with 125I and exhibited high radiostability. Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were formed by solvent exchange, and displayed spherical morphology of 100 nm in diameter as characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). A 2.5-fold greater uptake of 125I-radiolabelled SN-38-loaded folate-decorated PLGA nanoparticles (125I-SN-38-FA-NPs) than 125I-radiolabelled SN-38-loaded PLGA nanoparticles (125I-SN-38-NPs) were record in MKN7 tumor cells. NPs and folate-decorated PLGA nanoparticles (FA-NPs) also had good biocompatibility in methyl thiazolyl tetrazolium (MTT) assays. Pharmacokinetic, biodistribution and SPECT imaging studies showed that 125I-SN-38-FA-NPs had prolonged circulation, were distributed in the reticuloendothelial system, and had high uptake in tumors with a higher tumor accumulation of 125I-SN-38-FA-NPs than 125I-SN-38-NPs recorded at 24 h postinjection. In vivo SN-38-FA-NPs significantly inhibited tumor growth without causing obvious side effects. Conclusion: Folate receptor alpha (FOLR1) targeted drug-loaded nanoparticles enable SPECT imaging and chemotherapy, and provide a novel nanoplatform for gastric carcinoma active targeting theranostics.


Assuntos
Carcinoma , Nanopartículas , Neoplasias Gástricas , Linhagem Celular Tumoral , Portadores de Fármacos , Receptor 1 de Folato , Ácido Fólico/farmacologia , Humanos , Irinotecano , Tamanho da Partícula , Polietilenoglicóis , Medicina de Precisão , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Distribuição Tecidual
20.
J Gastrointest Surg ; 26(8): 1585-1595, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35585422

RESUMO

INTRODUCTION: The incidence of adenocarcinoma of esophageal-gastric junction (AEJ) has been increasing in recent years. Esophagogastrostomy after proximal gastrectomy (PG-EG) is the most commonly used surgical method for this disease which causes a constant spasm of the pyloric sphincter by cutting the vagus nerve around the esophagus, so H-M pyloroplasty (Heineke-Mikulicz pyloroplasty) is often operated after PG-EG to prevent delayed gastric emptying. However, H-M pyloroplasty destroys anti-reflux structure of pylorus and leads to serious bile reflux. The present study was designed to compare pyloromyotomy and H-M pyloroplasty in proximal subtotal gastrectomy through clinical studies and animal experiments. METHODS: We retrospectively evaluated the outcomes of 73 AEJ patients (39 underwent PG-EG with an H-M pyloroplasty and 34 underwent PG-EG with a pyloromyotomy) between January 2016 and August 2020, and perioperative variables were compared. In the animal experiment, 48 rats were randomly divided into four groups (n = 12): vagotomy group (V group), H-M pyloroplasty group (HM group), pyloromyotomy group (PM group), and control group (O group). Gastric emptying and bile reflux were evaluated in each group. RESULTS: In the retrospective clinic study, pyloromyotomy and H-M pyloroplasty could all prevent delayed gastric emptying effectively, and the incidence of bile reflux found by electronic gastroscopy in the PM group was significantly lower than that in the HM group (HM, 14/39; PM, 4/34; P = 0.028). In the animal experiment, there was no significant between-group difference of gastric emptying rate (%) in the HM group and PM group (HM, 70.6 ± 16; PM, 72.3 ± 12; P = 0.68) while the gastric emptying rate (%) was significantly lower in the V group than in the HM, PM, and control group (P values were 0.037, 0.021, and 0.001 respectively). The gastric mucosa bile acid concentration was significantly higher in the HM group than other group (P values were all less than 0.001). CONCLUSIONS: The pyloromyotomy could prevent delayed gastric emptying effectively after PG-EG for types II and III AEJ and reduce bile reflux compared to Heineke-Mikulicz pyloroplasty.


Assuntos
Adenocarcinoma , Refluxo Biliar , Gastroparesia , Piloromiotomia , Adenocarcinoma/cirurgia , Animais , Esôfago , Gastrectomia , Esvaziamento Gástrico , Gastroparesia/cirurgia , Piloro/cirurgia , Ratos , Estudos Retrospectivos
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