Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 378
Filter
1.
Article | IMSEAR | ID: sea-234164

ABSTRACT

Artificial sweeteners like Aspartame are popular due to their low caloric value. They are used as a substitute for sugar, especially for individuals with diabetes and obesity. However, its effects on the neurological system have been debated. Studies suggest aspartame metabolism can lead to altered neurotransmitter synthesis. This review aims to gather literature on the neurotoxic effects of aspartame in humans, aiming to curb this problem. The review was conducted using PubMed, Europe PMC, Cochrane, and Google Scholar. The quality and risk of bias of the extracted studies were assessed using the Critical Appraisal Skills Programme (CASP) checklist, specifically designed for Randomized Controlled Trials (RCTs). The systematic review of aspartame consumption was conducted using PRISMA guidelines and included 11 articles. The studies investigated the effects of aspartame consumption on behavior, cognition, and neurological function through RCTs of varying durations and across different age groups. Aspartame was the primary intervention in all studies, with some neuro biomarkers assessed mainly phenylalanine and tyrosine levels. While some studies reported negative impacts on the above-mentioned parameters others found no significant adverse effects. The review of studies on the effects of aspartame consumption on behavior, cognition, and neurological function reveals mixed results. Neurobiomarkers, specifically phenylalanine and tyrosine, were not consistently assessed across all investigations, making it difficult to establish a clear link between aspartame consumption and neurobiological changes. The studies reviewed provide valuable insights into aspartame effects but highlight complexity. Further research is needed to address limitations.

2.
Article in Chinese | WPRIM | ID: wpr-1017317

ABSTRACT

Objective:To discuss the differential effects of apolipoprotein E(APOE)gene polymorphism in the neurotoxicity-reactive astrocytes,and to provide the theoretical basis for the study of the pathogenesis of Alzheimer's disease(AD).Methods:The primary cortical astrocytes from the APOE-knockout mice(APOE-/-)were isolated and cultured in vitro,and the purity of the cells was identified by immunofluorescence staining.The human APOE3 and APOE4 recombinant over-expression plasmids were constructed and separately transfected into the primary APOE-/-astrocytes,and the APOE-/-primary cells were regarded as control.Western blotting method was used to detect the expression levels of APOE and glial fibrillary acidic protein(GFAP)proteins in the cells;enzyme-linked immunosorbent assay(ELISA)method was used to detect the APOE level in the cellular culture supernatant.The inflammatory models were prepared with the primary astrocytes transfected with APOE3 and APOE4 and co-stimulated with interleukin-1α(IL-1α),tumor necrosis factor(TNF),and complement C1q.The cells were divided into APOE3+PBS group,APOE4+PBS group,APOE3+IL-1α+TNF+ C1q group,and APOE4+IL-1α+TNF+C1q group.Cell immunofluorescence staining method was used to observe the morphology of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of glypican 4(Gpc4),glypican 6(Gpc6),thrombospondin 1(Thbs1),thrombospondin 2(Thbs2),SPARC-like protein 1(Sparcl1)and glial cell line derived neurotrophic factor(GDNF),C3,and S100 calcium binding protein B(S100B)mRNA in the cells in various groups;microsphere phagocytosis assay was used to detect the phagocytic capacities of the cells in various groups;Western blotting was used to detect the protein expression levels of B-cell lymphoma 2(Bcl-2),and cysteinyl aspartate specific protease-3(Caspase-3)proteins in the cells in various groups.Results:Compared with APOE-/-group,the expression levels of APOE and GFAP proteins in the cells and the APOE level in the cellular culture supernatant in transfected APOE3 and transfected APOE4 groups were increased(P<0.01).The fluorescence microscope observation results showed that compared with APOE3+PBS and APOE4+PBS groups,the astrocytic processes in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α+TNF+Cq1 group became shorter and the cell bodies became larger;compared with APOE3+IL-1α +TNF+Cq1 group,the astrocytic processes in APOE4+IL-1α +TNF+Cq1 group were even shorter.Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.05 or P<0.01).Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of GDNF mRNA in the cells in APOE3+IL-1α+TNF+Cq1 group and APOE4+ IL-1α +TNF+Cq1 group were decreased(P<0.01),and the expression levels of C3 and S100B mRNA were increased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression level of GDNF mRNA in the cells in APOE4+IL-1α+TNF+Cq1 group was decreased(P<0.05),and the expression levels of C3 and S100B mRNA were increased(P<0.05).Compared with APOE3+ PBS group and APOE4+PBS group,the numbers of hagocytosis of microspheres in the cells in APOE3+ IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased;compared with APOE3+IL-1α+TNF+Cq1 group,the number of hagocytosis of microspheres in the cells in APOE4+IL-1α+TNF+Cq1 group was significantly decreased.Compared with APOE3+PBS group and APOE4+PBS group,the expression levels of Bcl-2 protein in the cells in APOE3+IL-1α+TNF+ Cq1 group and APOE4+IL-1α +TNF+Cq1 group were decreased(P<0.05 or P<0.01)and the expression levels of Caspase-3 protein were significantly increased(P<0.01);compared with APOE3+ IL-1α+TNF+Cq1 group,the expression level of Bcl-2 protein in the cells in APOE4+IL-1α+TNF+ Cq1 group was decreased(P<0.01),and the expression level of Caspase-3 protein was increased(P<0.05).Conclusion:The APOE4 genotype has a stronger ability to induce the inflammatory factors compared with APOE3;it can lead to a neurotoxicity-reactive astrocyte phenotype,increase the neurotoxicity,affect the astrocyte apoptosis,and aggravate the neuron damage.

3.
Chongqing Medicine ; (36): 139-144, 2024.
Article in Chinese | WPRIM | ID: wpr-1017453

ABSTRACT

Methamphetamine use disorder is an ongoing global public health problem with complex mechanisms involving multiple neural circuits and neurotransmitters in the brain,and there are currently no effective drugs and methods to treat it.This article reviews the role of endoplasmic reticulum stress in meth-amphetamine use disorder and discusses the treatment strategies that can be used to mitigate the methamphet-amine-induced neurotoxic damage,which will contribute to the exploration of methamphetamine use disorder mechanisms and the development of new target drugs.

4.
China Pharmacy ; (12): 348-352, 2024.
Article in Chinese | WPRIM | ID: wpr-1006622

ABSTRACT

OBJECTIVE To provide reference for clinically safe drug use by mining oxaliplatin-related adverse drug events (ADE) of the nervous system. METHODS Oxaliplatin-related neurologic ADE data reported by the FDA adverse event reporting system (FAERS) between January 1st, 2004 and December 31st, 2022 were collected. The reporting odds ratio and proportional reporting ratio were used for data mining. The data were classified statistically by using systematic organ classification, high-level group term (HLGT) and preferred term (PT) in the MedDRA (version 26.0). RESULTS A total of 7 266 cases of oxaliplatin- related ADE, which were classified as various neurological, were retrieved, and 100 PT were identified. Of these, fifty-seven PT were unspecified adverse reaction signals in the manual. Among these reports, males (46.85%) were more than females (42.98%), the age of patients was 45-<75 years (65.22%), the number of reports was highest in Italy (16.32%), and the severe type was hospitalization or prolonged hospitalization (38.16%). The top 5 PT reports in the list of case number were peripheral neuropathy, paresthesia, neurotoxicity, loss of consciousness and dysarthria. The top 5 PT reports in the list of signal intensities were cold- induced paresthesia, neuromuscular rigidity, acute polyneuropathy, neuronal neuropathy, axonal and demyelinating polyneuropathy. A total of 13 HLGT were involved, with neurological diseases (not classified separately) having the highest number of signals (29). CONCLUSIONS When using oxaliplatin in clinical practice, it is not only necessary to monitor the high incidence of acute and chronic peripheral neuropathy, but also to pay attention to the patient’s consciousness state and neurological symptoms. We should pay attention to the rare types of adverse reactions, such as guillain-barre syndrome, Lhermitte sign, posterior reversible encephalopathy syndrome, and hyperammoniacal encephalopathy, so as to ensure the safety of medication.

5.
Article in Chinese | WPRIM | ID: wpr-1039156

ABSTRACT

Objective To observe the toxicity of low concentration Mn2+ compound combined with autophagy inhibitor chloroquine on nerve cell line PC12 cells for long-term and its mechanism. Methods PC12 cells at logarithmic growth stage were treated with 0 (control), 5, 10, 25, 50, 100, and 200 μM manganous chloride, and 5, 10, 25, 50, and 100 μM chloroquine for 24 h, respectively. The effect of manganous chloride and chloroquine on cell viability was detected by MTT assay. The combined effect of the two compounds on cell viability was determined at 24, 48 and 72 h, respectively. The mitochondrial respiratory function was further examined to explore the possible toxicity mechanism of manganous chloride and chloroquine. Results Compared with the control group, manganous chloride and chloroquine alone had inhibitory effect on cells survival in a concentration-dependent manner. Manganous chloride and chloroquine at concentrations of 40 μM and 2.5 μM, respectively, had no significant effect on cell survival. Compared with the control group, administration of 2.5 μM chloroquine alone for 24, 48 and 72 h did not significantly change cell survival and mitochondrial respiratory function. Treatment of cells with manganous chloride alone at the concentration of 40 μM for 72 h did affect mitochondrial respiratory function. However, the cell survival and mitochondrial respiratory function in the combined administration of manganous chloride and chloroquine for 72 h were significant decreased (P< 0.05). Conclusion The long-term combination of low-concentration manganous chloride and chloroquine produced an additive cytotoxicity on PC12 cells, and the toxicity mechanism may be related to the damage of mitochondrial function.

6.
Article in Chinese | WPRIM | ID: wpr-1039906

ABSTRACT

Background Nano-alumina (nano-Al2O3) is a widely utilized nanomaterial. Its impacts on the environment and biological systems have garnered significant attention. Zebrafish serves as a common model organism in scientific research due to its high homology with the human genome and is extensively used in toxicity studies. Objective To investigate the developmental toxicity and neurotoxicity of nano-Al2O3 exposure in zebrafish and the corresponding mechanisms of action. Method Zebrafish embryos at 6 h post-fertilization (hpf) were randomly assigned to a control group and five dose groups exposed to nano-Al2O3 at concentrations of 200, 400, 600, 800, and 1000 μg·mL−1, respectively. Thirty embryos were included in each group, and the culture medium was replaced every 24 h until 144 hpf. The hatching rates at 48 and 72 hpf and the cumulative malformation rates up to 144 hpf were calculated. At 144 hpf, a zebrafish behavior analyzer was used to record the movement trajectories of the zebrafish, and the total distance traveled and average speed were analyzed for each group. At 144 hpf, the development of dopaminergic neurons in transgenic zebrafish expressing vmat2: GFP, brain vessels in those expressing vegf: GFP, and central nervous system neurons in those expressing elavl3: EGFP were observed under a fluorescence microscope, and statistical analysis was conducted using Image Pro Plus. Real-time quantitative PCR was employed to detect the expression levels of neuron development-related genes (syn2α, gap43, dat), Lewy body formation-related gene (α-syn), and autophagy-related genes (pink1, parkin) at 144 hpf. Results Compared to the control group, the nano-Al2O3 exposed groups exhibited reduced hatching rates at 48 hpf and increased cumulative malformation rates (P<0.05), with phenomena such as delayed development, absence of the swim bladder, and body curvature. The autonomous behavioral tests revealed that the nano-Al2O3 exposed zebrafish showed a decrease in the total distance swum (P<0.001) and a significant reduction in average speed compared to the control group. The fluorescence observations indicated that the length of dopaminergic neurons in vmat2: GFP transgenic zebrafish was reduced in the nano-Al2O3 exposed groups (P<0.001). Additionally, vegf: GFP transgenic zebrafish exhibited a significant absence of brain vessels, while elavl3: EGFP transgenic zebrafish showed a weakened fluorescence intensity of central nervous system neurons (P<0.001) and a decreased length of these neurons (P<0.01). The real-time quantitative PCR analysis revealed that compared to the control group, the gene expression levels of α-syn, syn2α, dat, and gap43 were upregulated in the zebrafish exposed to nano-Al2O3 (except for the 400 μg·mL−1 exposure group) (P<0.01), while the expression levels of parkin were downregulated in the 600 and 800 μg·mL−1 nano-Al2O3 exposed groups, and the expression levels of pink1 were downregulated in all exposure groups except for the 200 μg·mL−1 group (P<0.05). Conclusion Exposure to nano-Al2O3 exhibits developmental toxicity in zebrafish larvae and induces Parkinsonism-like symptoms in zebrafish. The preliminary speculation of the mechanism suggests that it may be related to nano-Al2O3-induced mitochondrial autophagy impairment.

7.
Chinese Journal of Endemiology ; (12): 157-160, 2024.
Article in Chinese | WPRIM | ID: wpr-1024002

ABSTRACT

Arsenic, as a toxic substance that can affect human health, can cause various neurological disorders, including cognitive impairment, when excessive. Relevant epidemiological surveys and animal experimental studies have shown that exposure to arsenic can not only cause intellectual impairment and peripheral neuropathy in humans, but also lead to abnormal behavior in humans and animals. However, so far, the mechanism of arsenic induced damage to the nervous system is still unclear. Peroxisome proliferator activated receptor γ auxiliary activation factor 1α (PGC-1α), as a nuclear transcription coactivator, can interact with transcription factors or other coactivators and plays a role in biological processes such as mitochondrial biogenesis and energy metabolism. PGC-1α, by activating mitochondrial biogenesis, affecting energy metabolism, activating oxidative stress regulatory factors [catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), etc.], mitigates the damage to the central nervous system (CNS), peripheral nervous system (PNS), and blood-brain barrier (BBB) caused by arsenic. This article summarize the research progress of arsenic-induced neurological injury and the mechanism of PGC-1α's role in arsenic-induced neurological injury to provide a theoretical basis for further prevention and treatment of neurological diseases caused by arsenic.

8.
Article in Chinese | WPRIM | ID: wpr-1025121

ABSTRACT

Methamphetamine(METH)is highly addictive and neurotoxic,which causes cognitive and memory dysfunction in abusers.The harm of METH lies not only in its own toxicity,but also in the high physical and mental dependence of drug addicts,often causing mental disorders and violent behavior,bringing great safety risks to society.Non-coding RNA(ncRNA)does not encode proteins and is an important factor in regulating gene expression at the post-transcriptional level.Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity,but the specific mechanism is unclear.This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity to provide a reference for ncRNA as a forensic identification index and potential therapeutic target for METH abusers.

9.
Med. infant ; 30(3): 270-273, Septiembre 2023. ilus, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1515962

ABSTRACT

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)


Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)


Subject(s)
Humans , Child, Preschool , Child , Adolescent , Neurotoxicity Syndromes/diagnosis , Neurotoxicity Syndromes/etiology , Ifosfamide/adverse effects , Neoplasms/drug therapy , Seizures/chemically induced , Incidence , Cross-Sectional Studies , Retrospective Studies , Antineoplastic Agents, Alkylating/adverse effects
10.
Medicina (B.Aires) ; Medicina (B.Aires);83(3): 471-474, ago. 2023. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1506703

ABSTRACT

Resumen Los inhibidores del punto de control inmunitario han demostrado mejorar el pronóstico de múltiples enfer medades oncológicas. Recientemente se han reportado eventos adversos relacionados a la inmunoterapia. La to xicidad neurológica es poco frecuente. Se presenta el caso de un paciente con encefalitis relacionada con inhibido res del punto de control inmunitario.


Abstract Immune checkpoint inhibitors have been shown to improve the prognosis of multiple oncological diseases. Recently, adverse events related to immunotherapy have been reported. Neurologic toxicity is infrequent. We pre sent the case of a patient with encephalitis associated to immune checkpoint inhibitors.

11.
Article | IMSEAR | ID: sea-218915

ABSTRACT

Lead is a dangerous element that exists naturally in the Earth's crust. Any kind of lead causes a detrimental response in the human body. It is discharged into the environment during the manufacturing of batteries, foundries, ammunition, lead paint, water pipes, and other manufactured goods. It can enter the body through a variety of pathways, including those in the air, water, soil, food, and dust. Concern is raised since there is no amount of lead that is safe for the human body. The problem persists despite several prevention measures that the state and the federal governments have put in place. This review assesses the effects of lead exposure on children as well as suggested solutions to the issue.

12.
Medwave ; 23(4): e2664, 31-05-2023.
Article in English | LILACS-Express | LILACS | ID: biblio-1436192

ABSTRACT

Early T-cell precursor Acute Lymphoblastic Leukemia (ALL) has a dismal prognosis. Nelarabine is a purine nucleoside analog that increases the apoptosis rate in T-cell lymphoblasts. We present a 30-year-old patient diagnosed with T-cell ALL. He was a high-risk patient because of an early precursor phenotype and a complex karyotype that had been refractory to three previous lines of treatment. He started a course of nelarabine (1500 mg/m for three days), pegylated-asparaginase, doxorubicin, vincristine, and prednisone (Nelarabine Peg-Asp AdmVP). He reached complete remission and received an allogeneic sibling hematopoietic stem cell transplant with fludarabine, total body irradiation, and cyclophosphamide as the conditioning regimen. He developed a pulmonary mycosis, which resolved, and grade-2 neurotoxicity in his upper and lower limbs. He was discharged after 40 days and to date remains with 23 months of complete remission. The Nelarabine Peg-Asp AdmVP regimen seems to be effective and safe. Further research is needed to establish it as an induction treatment in refractory early T-cell precursor acute lymphoblastic leucemia.

13.
Arch. argent. pediatr ; 121(2): e202202649, abr. 2023. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1424954

ABSTRACT

El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.


Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.


Subject(s)
Humans , Male , Child , Adolescent , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/pathology , Neurotoxicity Syndromes/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Lymphoma , Magnetic Resonance Imaging , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/adverse effects
14.
China Pharmacy ; (12): 251-256, 2023.
Article in Chinese | WPRIM | ID: wpr-959758

ABSTRACT

In recent years, neurotoxicity caused by traditional Chinese medicine (TCM) has frequently occurred and has become one of the important factors restricting the development and application of TCM. TCM contains active components and its dosage-effect relationship is the key to determine its pharmacological activity and toxic effects. Among them, the endogenous toxic components include alkaloids, glycosides, diterpenoids, animal and plant toxic proteins and heavy metals, and so on; exogenous toxic components mainly refer to some harmful elements and pesticide residues during the cultivation, processing, transportation and storage of medicinal materials that are not synthesized by themselves. Effect on the processes such as oxidative stress, inflammation, ion exchange, and energy metabolism may be important mechanisms of TCM-induced neurotoxicity. Neural cells, myelin cells, axons and neurotransmitter systems are common targets of TCM-induced neurotoxicity. In the future, we can use modern research methods and big data mining means to establish a safety evaluation mode of “toxic symptoms-poisoning dose-toxic original agent-detoxification scheme” with the basic component group of toxic substances as the core, so as to provide support for development and clinical intervention of neurotoxic traditional Chinese medicine.

15.
Article in Chinese | WPRIM | ID: wpr-979204

ABSTRACT

Aluminum is a light metal which is rich in the earth's crust and widely used. Recently, the adverse health effects of environmental and occupational aluminum exposure on human have attracted more and more attention. Aluminum exposure has toxic effects on the central nervous system and is believed to be closely related to the development and progression of Alzheimer's disease. The neurotoxic mechanism of aluminum is complex, especially the role of regulated cell death (RCD) in aluminum-induced neuronal death remains to be further studied. RCD refers to all modes of cell death regulated by multiple intracellular signal transduction pathways under physiological and pathological conditions, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. This review summarized the morphological characteristics and mechanisms of each RCD mode in the process of aluminum-induced neuronal death, and discussed the relationship and transformation between different RCD modes, providing a new scientific basis for future studies on the treatment and intervention of neurotoxicity induced by aluminum exposure.

16.
Journal of Pharmaceutical Analysis ; (6): 1510-1525, 2023.
Article in Chinese | WPRIM | ID: wpr-1023132

ABSTRACT

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme(CYP),which plays a crucial role in the metabolism of neurosteroids.The antiepileptic drug phenytoin(PHT)has been observed to induce neuronal side effects in patients,which could be attributed to its induction of CYP expression and testosterone(TES)metabolism in the hip-pocampus.While pregnane X receptor(PXR)is widely known for its regulatory function of CYPs in the liver,we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile(PCN),a PXR agonist,has differential effects on CYP expression in the liver and hippocampus.Specifically,the PCN treatment resulted in the induction of cytochrome P450,family 3,subfamily a,polypeptide 11(CYP3A11),and CYP2B10 expression in the liver,while suppressing their expression in the hippocampus.Func-tionally,the PCN treatment protected mice from PHT-induced hippocampal nerve injury,which was accompanied by the inhibition of TES metabolism in the hippocampus.Mechanistically,we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent,rather than PXR independent,as demonstrated by genetic and pharmacological models.In conclusion,our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR.Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

17.
Article in Chinese | WPRIM | ID: wpr-1031965

ABSTRACT

@#Alzheimer's disease (AD) is a progressive neurodegenerative disease with memory impairment as the main manifestation. With the development of an aging society,the incidence of AD is on the rise,bringing a huge social and economic burden. In recent years,the classical amyloid cascade hypothesis in the pathogenesis of AD has been challenged,and the toxic effects of Aβ oligomers (AβOs) have been consistently recognized,which may be a trigger for the pathogenesis of AD. The specific source,structure,and pathogenic mechanism of Aβ oligomers are not fully understood. It is possible that different types of oligomers are not consistent in pathogenicity and toxicity,and their mechanisms of action are different. This article reviews the recent understanding of Aβ oligomers,as well as their structural characteristics and pathogenic effects,to better understand the relationship between Aβ oligomers and AD,and provide possible directions for future research.

18.
Chinese Journal of Neuromedicine ; (12): 973-983, 2023.
Article in Chinese | WPRIM | ID: wpr-1035907

ABSTRACT

Objective:To investigate the influence of long non-coding RNA (lncRNA) DIO3OS in ketamine-induced neurotoxicity and its mechanism in mouse hippocampal neurons.Methods:(1) Primary mouse hippocampal neurons were isolated and cultured; CCK-8 assay was used to detect the viability of cells treated with different concentrations of ketamine (0, 25, 50, 100, 200 μmol/L), and qPCR was used to detect DIO3OS mRNA expression. (2) Hippocampal neurons were divided into 4 groups: control group, ketamine group (cultured with 50 μmol/L ketamine for 24 h), ketamine+pc group (transfected with pcDNA3.1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), and ketamine+DIO3OS group (transfected with pcDNA3.1-DIO3OS plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); cell viability was detected by CCK-8 assay; lactic dehydrogenase (LDH) release was determined by LDH cytotoxicity assay kit; cell apoptosis was detected by flow cytometry; mRNA expressions of DIO3OS and brain-derived neurotrophic factor ( BDNF) were examined by qPCR; protein expressions of polypyrimidine tract-binding protein 1 (PTBP1) and BDNF were detected by Western blotting. (3) Total proteins of routinely cultured neurons were extracted, and RNA Pull-Down assay was used to detect whether DIO3OS mRNA and BDNF mRNA could directly bind to PTBP1 protein. (4) Hippocampal neurons were divided into ketamine+DIO3OS+si-NC group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-NC plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h) and ketamine+DIO3OS+si-PTBP1 group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-PTBP1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); qPCR was used to examine the mRNA expressions of DIO3OS and BDNF; Western blotting was used to detect the protein levels of PTBP1 and BDNF. (5) Hippocampal neurons were divided into ketamine group (cultured with 50 μmol/L ketamine for 24 h), ketamine+si-DIO3OS group (transfected with si-DIO3OS plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), ketamine+si-PTBP1 group (transfected with si-PTBP1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), and ketamine+si-DIO3OS+si-PTBP1 group (co-transfected with si-DIO3OS plasmid and si-PTBP1 plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); qPCR was used to examine the mRNA expressions of DIO3OS and BDNF; Western blotting was used to detect the BDNF protein expression. (6) Hippocampal neurons were divided into ketamine+DIO3OS+si-NC group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-NC plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h), ketamine+DIO3OS+si-BDNF group (co-transfected with pcDNA3.1-DIO3OS plasmid and si-BDNF plasmid for 48 h, and then cultured with 50 μmol/L ketamine for 24 h); cell viability was detected by CCK-8 assay; LDH release was determined by LDH cytotoxicity assay kit; cell apoptosis was detected by flow cytometry. Results:(1) Compared with 0 μmol/L ketamine, 25, 50, 100 and 200 μmol/L ketamine could significantly inhibit the cell viability and DIO3OS mRNA expression ( P<0.05). (2) Compared with control group, ketamine group had significantly decreased DIO3OS mRNA expression and cell viability, significantly increased LDH release and apoptotic rate, and statistically inhibited BDNF mRNA and protein expressions and PTBP1 protein expression ( P<0.05); compared with ketamine+pc group, ketamine+DIO3OS group had significantly increased DIO3OS mRNA expression and cell viability, significantly decreased LDH release and apoptotic rate, significantly elevated BDNF mRNA and protein expressions ( P<0.05). (3) RNA Pull-Down assay showed that Bio-labeled DIO3OS (Bio-DIO3OS) and Bio-labeled BDNF (Bio-BDNF) could adsorb PTBP1 protein, while Bio-labeled antisense strands of DIO3OS or BDNF (Bio-DIO3OS-AS and Bio-BDNF-AS) could not adsorb PTBP1 protein. (4) Compared with ketamine+DIO3OS+si-NC group, ketamine+DIO3OS+si-PTBP1 group had significantly inhibited BDNF mRNA and protein expressions and PTBP1 protein expression ( P<0.05); no significant difference was noted in DIO3OS mRNA expression ( P>0.05). (5) Compared with ketamine group, ketamine+si-DIO3OS and ketamine+si-DIO3OS+si-PTBP1 groups had significantly decreased DIO3OS mRNA expression ( P<0.05); compared with ketamine group, ketamine+si-DIO3OS and ketamine+si-PTBP1 groups had significantly decreased BDNF mRNA and protein expressions ( P<0.05); compared with ketamine+si-DIO3OS and ketamine+si-PTBP1 groups, ketamine+si-DIO3OS+si-PTBP1 group had significantly elevated BDNF mRNA and protein expressions ( P<0.05). (6) Compared with ketamine+DIO3OS+si-NC group, ketamine+DIO3OS+si-BDNF group had significantly reduced cell viability, and significantly increased LDH release and apoptotic rate ( P<0.05). Conclusion:LncRNA DIO3OS expression is decreased in ketamine-induced primary mouse hippocampal neurons; DIO3OS overexpression can alleviate ketamine-induced neurotoxicity in mouse hippocampal neurons by regulating BDNF expression via binding to PTBP1.

19.
Article in Chinese | WPRIM | ID: wpr-976206

ABSTRACT

@#Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC). CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified. However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines. Remarkable increase of cytokine level is a major characteristics of CRS. However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction. CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients. Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients. This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.

20.
Zhongguo Zhong Yao Za Zhi ; (24): 4610-4619, 2023.
Article in Chinese | WPRIM | ID: wpr-1008628

ABSTRACT

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.


Subject(s)
Humans , Medicine, Chinese Traditional , Oxaliplatin/adverse effects , Artificial Intelligence , Quality of Life , Drugs, Chinese Herbal/therapeutic use , Antineoplastic Agents/adverse effects , Cognition
SELECTION OF CITATIONS
SEARCH DETAIL