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1.
Neuromolecular Med ; 26(1): 22, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824254

RESUMO

Stroke is a significant public health issue, and research has consistently focused on studying the mechanisms of injury and identifying new targets. As a CDK5 activator, p39 plays a crucial role in various diseases. In this article, we will explore the role and mechanism of p39 in cerebral ischemic injury. We measured the level of p39 using western blot and QPCR at various time points following cerebral ischemia-reperfusion (I/R) injury. The results indicated a significant reduction in the level of p39. TTC staining and behavioral results indicate that the knockout of p39 (p39KO) provides neuroprotection in the short-term. Interestingly, the behavioral dysfunction in p39KO mice was exacerbated after the repair phase of I/R. Further study revealed that this deterioration may be due to demyelination induced by elevated p35 levels. In summary, our study offers profound insights into the significance of p39 in both the acute and repair stages of ischemic injury recovery and a theoretical foundation for future therapeutic drug exploration.


Assuntos
Camundongos Endogâmicos C57BL , Camundongos Knockout , Bainha de Mielina , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/genética , Infarto da Artéria Cerebral Média/patologia , Fosfotransferases , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
2.
Medicine (Baltimore) ; 103(18): e38086, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701247

RESUMO

BACKGROUND: Dementia is a major public health challenge for aging societies worldwide. Neuroinflammation is thought to be a key factor in dementia development. The aim of this study was to comprehensively assess translocator protein (TSPO) expression by positron emission tomography (PET) imaging to reveal the characteristics of neuroinflammation in dementia. METHODS: We used a meta-analysis to retrieve literature on TSPO expression in dementia using PET imaging technology, including but not limited to the quality of the study design, sample size, and the type of TSPO ligand used in the study. For the included studies, we extracted key data, including TSPO expression levels, clinical characteristics of the study participants, and specific information on brain regions. Meta-analysis was performed using R software to assess the relationship between TSPO expression and dementia. RESULTS: After screening, 12 studies that met the criteria were included. The results of the meta-analysis showed that the expression level of TSPO was significantly elevated in patients with dementia, especially in the hippocampal region. The OR in the hippocampus was 1.50 with a 95% CI of 1.09 to 1.25, indicating a significant increase in the expression of TSPO in this region compared to controls. Elevated levels of inflammation in the prefrontal lobe and cingulate gyrus are associated with cognitive impairment in patients. This was despite an OR of 1.00 in the anterior cingulate gyrus, indicating that TSPO expression in this region did not correlate significantly with the findings. The overall heterogeneity test showed I² = 51%, indicating moderate heterogeneity. CONCLUSION: This study summarizes the existing literature on TSPO expression in specific regions of the brain in patients with dementia, and also provides some preliminary evidence on the possible association between neuroinflammation and dementia. However, the heterogeneity of results and limitations of the study suggest that we need to interpret these findings with caution. Future studies need to adopt a more rigorous and consistent methodological design to more accurately assess the role of neuroinflammation in dementia, thereby providing a more reliable evidence base for understanding pathological mechanisms and developing potential therapeutic strategies.


Assuntos
Demência , Doenças Neuroinflamatórias , Tomografia por Emissão de Pósitrons , Receptores de GABA , Humanos , Tomografia por Emissão de Pósitrons/métodos , Demência/diagnóstico por imagem , Demência/metabolismo , Receptores de GABA/metabolismo , Doenças Neuroinflamatórias/diagnóstico por imagem , Doenças Neuroinflamatórias/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo
3.
Oncol Lett ; 27(2): 54, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38192653

RESUMO

Interleukin (IL)-32 is induced by pro-inflammatory cytokines and promotes the release of inflammatory cytokines. Therefore, it can promote inflammatory responses. The present review article summarized the role of the receptors required for IL-32 action, the biological function of IL-32 and its mechanism of action in tumors. Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.

5.
Front Neurosci ; 16: 986860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203809

RESUMO

Objective: In this study, clinical data from vestibular migraine (VM) patients and healthy control populations were collected to analyze the clinical data of VM patients, especially the history of motion sickness, and to understand their clinical characteristics. Methods: According to VM diagnostic criteria, 140 patients diagnosed with confirmed VM (cVM) and probable VM (pVM) who attended the outpatient and inpatient ward of Jiaxing First Hospital between August 2017 and June 2021, as well as 287 healthy check-ups in the health management center, were analyzed and compared in terms of age, gender, and previous history of motion sickness. Results: A comparison of clinical data related to VM patients and the control population showed that there were more women in the VM group (P < 0.01) and that patients in the VM group were older (P < 0.05) and had a higher prevalence of history of motion sickness history (P < 0.01). Analysis after matching gender and age revealed that patients in the cVM group were older than those in the pVM group (P < 0.05), but the proportion of motion sickness was lower than in the pVM group (P < 0.05). The age of the patients in the cVM group was mainly distributed around 50 years of age, following a normal distribution, whereas the age distribution of the patients in the pVM group did not have a significant trend of age concentration and was distributed at all ages. Conclusion: The history of motion sickness is significant in patients with VM and may be a potential suggestive factor for the diagnosis of VM.

6.
Mol Pain ; 17: 17448069211042117, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34505815

RESUMO

BACKGROUND: Pain is an unpleasant sensory experience that usually plays a protective role. Inflammatory pain is often severe and stubborn, which has a great impact on the quality of life of patients. However, there has been no breakthrough in the treatment strategy and mechanism of inflammatory pain. METHODS: This study investigated the analgesic effect of tetrahydropalmatine (THP) in rats injected with complete Freund's adjuvant (CFA)-induced inflammatory pain. Allodynia and gait analysis of rats were used to evaluate the analgesic effect at different time points before and after operation. THP (2.5, 5, and 10 mg/kg) was administered intraperitoneally once daily for 7 days post Day 3. The expression levels of TNF-α and IL-1ß in the spinal cord were measured by enzyme-linked immunosorbent assay. The activation of astrocytes and microglial cells in the spinal cord was tested by western blot before and after THP treatment. The apoptosis of glial cells was tested by flow cytometry after treatment with THP in the primary cultured glial cell model. RESULTS: CFA treatment induced significant allodynia and caused abnormal gait in rats. Administration of THP at 10 mg/kg significantly alleviated CFA-induced inflammatory pain behaviors. Moreover, CFA-induced activation of glial cells and the increased levels of TNF-α and IL-1ß were inhibited by THP administration. In addition, THP promotes apoptosis in primary cultured glial cells. This study suggests the possible clinical utility of THP in the treatment of inflammatory pain. CONCLUSION: THP plays an analgesic role by inhibiting the activation of glial cells and promoting apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Alcaloides de Berberina/farmacologia , Inflamação/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Dor/tratamento farmacológico , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Adjuvante de Freund/efeitos adversos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Microglia/efeitos dos fármacos , Neuroglia/metabolismo , Dor/metabolismo , Ratos Sprague-Dawley , Medula Espinal/metabolismo
7.
Front Immunol ; 12: 688643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177942

RESUMO

C-type lectin-like receptor 2 (CLEC-2, also known as CLEC-1b) is expressed on platelets, Kupffer cells and other immune cells, and binds to various ligands including the mucin-like protein podoplanin (PDPN). The role of CLEC-2 in infection and immunity has become increasingly evident in recent years. CLEC-2 is involved in platelet activation, tumor cell metastasis, separation of blood/lymphatic vessels, and cerebrovascular patterning during embryonic development. In this review, we have discussed the role of CLEC-2 in thromboinflammation, and focused on the recent research.


Assuntos
Coagulação Sanguínea , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Lectinas Tipo C/metabolismo , Trombose/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Lectinas Tipo C/antagonistas & inibidores , Ligantes , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/imunologia
8.
Neurotox Res ; 39(2): 477-488, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33165736

RESUMO

C-type lectin-like receptor 2 (CLEC-2) is a platelet surface-activating receptor with the prominent involvement in platelet activation, which was found to be associated with the progression and prognosis of acute ischemic stroke patients. Although podoplanin is the only known endogenous ligand for CLEC-2, the role of podoplanin/CLEC-2 in cerebral ischemia injury was unclear. In this study, we examined their role by using a mouse middle cerebral artery occlusion (MCAO) model. The expression of CLEC-2 and podoplanin increased after ischemia/reperfusion (I/R) injury, peaked at 24 h, and then decreased gradually. Podoplanin and CLEC-2 co-localized mainly in the ischemia/reperfusion cortex and expressed on neurons and microglia. Anti-podoplanin antibody pretreatment reduced cerebral infarct volume from 52.67 ± 4.67 to 34.08 ± 6.04% (P < 0.05) and attenuated the neurological deficits during acute stage and recovery stage. Moreover, a significant decrease of IL-18 and IL-1ß was observed in the mice pretreated with the anti-podoplanin antibody. Our results demonstrate that the podoplanin-CLEC-2 axis might play an important role in cerebral ischemia/reperfusion injury in mice by promoting inflammatory reactions.


Assuntos
Encefalite/metabolismo , AVC Isquêmico/metabolismo , Lectinas Tipo C/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos ICR , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Traumatismo por Reperfusão/metabolismo
10.
Neuroscience ; 430: 1-11, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32014436

RESUMO

Depression is a serious global affective disorder and one of the most common neurological diseases. Tanshinone IIA (TSA) is the mainly active constituent of Salvia miltiorrhiza and has diverse biological effects, including anti-inflammatory and antioxidant effects and significant neuroprotective effects against cerebral ischemia and Alzheimer's disease. However, whether TSA has an antidepressant effect remains unknown. The present study attempted to explore the antidepressant effects and the mechanism of TSA by examining the brain-derived neurotrophic factor (BDNF) expression in the hippocampus of depressive mice. The tail suspension test (TST) and forced swim test (FST) showed that TSA can significantly reduce the immobility time of depressed mice. Chronic administration of TSA increased p-ERK and p-CREB, BDNF proteins in mice hippocampus. We further explored the potential mechanism of TSA' antidepressant effect. TSA significantly increased the expression of p-ERK, p-CREB and BDNF proteins in dexamethasone-treated PC12 cells, and this enhancement was suppressed by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor SL327. Moreover, we observed that SL327 treatment markedly suppressed the increased levels of p-ERK, p-CREB and BDNF in mice hippocampus induced by TSA, preventing the antidepressant effects of TSA. Taken together, our results suggest that the antidepressant-like effects of TSA were mediated by ERK-CREB-BDNF pathway in mice hippocampus.


Assuntos
Abietanos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Depressão/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular , Transdução de Sinais , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo/metabolismo , Camundongos , Ratos
11.
R Soc Open Sci ; 5(2): 171216, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29515840

RESUMO

In this study, enzymatic hydrolysis and cationization with epoxypropyldodecyldimethylammonium chloride of wheat protein, an economic protein complex containing great amount of disulfide bonds, were conducted to improve properties such as solubility and disassociation behaviour for recovery of damaged hair when used in shampoo. The optimal conditions for enzymatic hydrolysis were pH 8.2, 55°C with Alcalase for 60 min. After the selected hydrolysis, the degree of hydrolysis, nitrogen solubility index, foaming capacity index, foam stability index, emulsifying activity index and emulsion stability index of hydrolysate with 58.71% of short-chain peptides (less than 1000 Da) were 8.81%, 39.07%, 225%, 56.67%, 9.62 m2 g-1 and 49.08, respectively. The cationization was followed to raise the isoelectric point of wheat protein hydrolysate from 7.0 to 10.0, which could facilitate the quaternized protein hydrolysate to adhere to the surface of hair at the range of pH 5-6 of hair care products to form more disulfide bonds. The results show that a shampoo with quaternized wheat proteins hydrolysate possesses excellent properties in recovering damaged hair, making the surface of hair smooth and compact.

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