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1.
BMC Infect Dis ; 23(1): 742, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904093

RESUMO

BACKGROUND: Hydrocephalus is a frequent complication of tuberculous meningitis (TBM), and ventriculoperitoneal shunt (VPS) has been shown to improve short-term prognosis for patients with TBM-associated hydrocephalus. However, questions remain about long-term prognosis and shunt-related complications. This study aims to provide a comprehensive assessment of both long-term prognosis and shunt-related complications in patients with TBM-induced hydrocephalus who have undergone VPS treatment. METHODS: This retrospective study analyzed the clinical data of TBM patients with hydrocephalus treated with VPS at Peking Union Medical College Hospital between December 1999 and February 2023. Both short-term outcomes at discharge and long-term outcomes during follow-up were examined. Prognosis and shunt-related complications were assessed using the modified Rankin Scale (mRS) and the Activity of Daily Living (ADL) score to evaluate neurological function and autonomic living ability, respectively. RESULTS: A total of 14 patients with TBM-associated hydrocephalus were included in this study. Of these, 92.9% (13/14) exhibited favorable short-term outcomes, while 57.1% (8/14) showed positive long-term outcomes. Initial results indicated 6 complete recoveries (CR), 7 partial recoveries (PR), and 1 treatment failure. No catheter-related complications were observed initially. Long-term results included 4 CRs, 4 PRs, and 6 treatment failures. A variety of shunt surgery-related complications were noted, including three instances of catheter obstruction, one of incision infection, one of catheter-related infection, one of acute cerebral infarction, and one of transient peritoneal irritation accompanied by diarrhea. CONCLUSIONS: VPS appears to be an effective and well-tolerated treatment for TBM-associated hydrocephalus, efficiently alleviating acute intracranial hypertension. Nonetheless, continuous long-term monitoring and proactive management are essential to mitigate the risk of catheter-related complications.


Assuntos
Hidrocefalia , Tuberculose Meníngea , Humanos , Derivação Ventriculoperitoneal/efeitos adversos , Estudos Retrospectivos , Tuberculose Meníngea/complicações , Tuberculose Meníngea/cirurgia , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Prognóstico , Resultado do Tratamento
2.
J Nanobiotechnology ; 21(1): 396, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904204

RESUMO

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1ß, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software. RESULTS: A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1ß: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9). CONCLUSIONS: This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS. PROSPERO REGISTRATION NUMBER: CRD42022368744.


Assuntos
Vesículas Extracelulares , AVC Isquêmico , Animais , AVC Isquêmico/terapia , Interleucina-6 , Fator de Necrose Tumoral alfa , Infarto
3.
Neurooncol Adv ; 5(1): vdad117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841695

RESUMO

Background: The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments. Methods: To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide. Results: By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model. Conclusions: Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.

4.
Aging Dis ; 14(5): 1533-1554, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196120

RESUMO

Subarachnoid hemorrhage (SAH), classified as a medical emergency, is a devastating and severe subtype of stroke. SAH induces an immune response, which further triggers brain injury; however, the underlying mechanisms need to be further elucidated. The current research is predominantly focused on the production of specific subtypes of immune cells, especially innate immune cells, post-SAH onset. Increasing evidence suggests the critical role of immune responses in SAH pathophysiology; however, studies on the role and clinical significance of adaptive immunity post-SAH are limited. In this present study, we briefly review the mechanistic dissection of innate and adaptive immune responses post-SAH. Additionally, we summarized the experimental studies and clinical trials of immunotherapies for SAH treatment, which may form the basis for the development of improved therapeutic approaches for the clinical management of SAH in the future.

5.
Front Pharmacol ; 14: 1113182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033651

RESUMO

Introduction: Glioma is the most common primary brain tumor and primary malignant tumor of the brain in clinical practice. Conventional treatment has not significantly altered the prognosis of patients with glioma. As research into immunotherapy continues, glioma immunotherapy has shown great potential. Methods: The clinical data were acquired from the Chinese Glioma Genome Atlas (CGGA) database and validated by the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) dataset, Clinical Proteomic Tumor Analysis Consortium (CPTAP) database, and Western blot (WB) analysis. By Cox regression analyses, we examined the association between different variables and overall survival (OS) and its potential as an independent prognostic factor. By constructing a nomogram that incorporates both clinicopathological variables and the expression of URB2, we provide a model for the prediction of prognosis. Moreover, we explored the relationship between immunity and URB2 and elucidated its underlying mechanism of action. Results: Our study shows that URB2 likely plays an oncogenic role in glioma and confirms that URB2 is a prognostic independent risk factor for glioma. Furthermore, we revealed a close relationship between immunity and URB2, which suggests a new approach for the immunotherapy of glioma. Conclusion: URB2 can be used for prognosis prediction and immunotherapy of glioma.

6.
Front Immunol ; 13: 980378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531992

RESUMO

Background: Glioma is a fatal tumor originating from the brain, which accounts for most intracranial malignancies. Currently, Immunotherapy has turned into a novel and promising treatment in glioma patients. however, there are still few effective biomarkers to mirror the reaction to immunotherapy in patients with glioma. Therefore, we intended to elucidate the evaluable efficacy of SLC11A1 in glioma patients. Methods: In this study, samples from Shanghai General Hospital and data from TCGA, GEO, CGGA datasets were used to investigate and validate the relationship between SLC11A1 and the progression of glioma. We evaluated the predictive value of SLC11A1 on the prognosis of glioma with cox regression analysis. Then the relationship between immune infiltration and SLC11A1 was also analyzed. Ultimately, we performed the prediction on the immunotherapeutic response and therapeutic drugs according to the expression of SLC11A1. Results: Expression of SLC11A1 increased with progression and predicted unfavorable prognosis for glioma patients. The hazard ratio for SLC11A1 expression was 2.33 with 95% CI (1.92-2.58) (P < 0.001) in cox analysis. And based on expression, we found SLC11A1 stratified glioma patients into subgroups with different immune activation statuses. Moreover, we observed that patients with higher SLC11A1 levels companied with better immunotherapeutic response, while those with lower SLC11A1 levels may respond better to temozolomide. Conclusion: This study provided evidence that SLC11A1 was a novel prognostic marker and immunotherapy response indicator for gliomas. In some cases, SLC11A1 could be an effective marker for identifying patients who might benefit from immunotherapy or chemotherapy.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , China , Imunoterapia , Glioma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Temozolomida/uso terapêutico
7.
Front Surg ; 9: 971066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425889

RESUMO

Chronic internal carotid artery occlusion (CICAO) has high prevalence and incidence rates, and patients with CICAO can be completely asymptomatic, experience a devastating stroke or die. It is important to note that CICAO causes cerebrovascular accidents. Currently, the external carotid-internal carotid (EC-IC) bypass technique is used to treat CICAO. However, many clinical studies showed that EC-IC bypass was not beneficial for many patients with CICAO. Meanwhile, endovascular intervention treatment options for CICAO are evolving, and an increasing number of patients are undergoing endovascular intervention therapy. Accordingly, a review comparing both techniques is warranted. For this review, we searched PubMed and collected relevant case study reports comparing endovascular interventional therapy and internal and external cervical bypass surgeries to provide strategies for clinical treatment.

8.
Front Oncol ; 12: 989896, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249003

RESUMO

Ferroptosis is a regulatory form of iron-dependent cell death caused by the accumulation of lipid-based reactive oxygen species (ROS) and differs from apoptosis, pyroptosis, and necrosis. Especially in neoplastic diseases, the susceptibility of tumor cells to ferroptosis affects prognosis and is associated with complex effects. Gliomas are the most common primary intracranial tumors, accounting for disease in 81% of patients with malignant brain tumors. An increasing number of studies have revealed the particular characteristics of iron metabolism in glioma cells. Therefore, agents that target a wide range of molecules involved in ferroptosis may regulate this process and enhance glioma treatment. Here, we review the underlying mechanisms of ferroptosis and summarize the potential therapeutic options for targeting ferroptosis in glioma.

9.
Oxid Med Cell Longev ; 2022: 1949718, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105479

RESUMO

Stroke is a fatal cerebral vascular disease with a high mortality rate and substantial economic and social costs. ROS production and neuroinflammation have been implicated in both hemorrhagic and ischemic stroke and have the most critical effects on subsequent brain injury. SIRT1, a member of the sirtuin family, plays a crucial role in modulating a wide range of physiological processes, including apoptosis, DNA repair, inflammatory response, and oxidative stress. Targeting SIRT1 to reduce ROS and neuroinflammation might represent an emerging therapeutic target for stroke. Therefore, we conducted the present review to summarize the mechanisms of SIRT1-mediated oxidative stress and neuroinflammation in stroke. In addition, we provide a comprehensive introduction to the effect of compounds and natural drugs on SIRT1 signaling related to oxidative stress and neuroinflammation in stroke. We believe that our work will be helpful to further understand the critical role of the SIRT1 signaling pathway and will provide novel therapeutic potential for stroke treatment.


Assuntos
Sirtuína 1 , Acidente Vascular Cerebral , Humanos , Doenças Neuroinflamatórias , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico
10.
Front Oncol ; 12: 976557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046036

RESUMO

Glioma is the most common malignant intracranial tumor and exhibits diffuse metastasis and a high recurrence rate. The invasive property of glioma results from cell detachment. Anoikis is a special form of apoptosis that is activated upon cell detachment. Resistance to anoikis has proven to be a protumor factor. Therefore, it is suggested that anoikis resistance commonly occurs in glioma and promotes diffuse invasion. Several factors, such as integrin, E-cadherin, EGFR, IGFR, Trk, TGF-ß, the Hippo pathway, NF-κB, eEF-2 kinase, MOB2, hypoxia, acidosis, ROS, Hsp and protective autophagy, have been shown to induce anoikis resistance in glioma. In our present review, we aim to summarize the underlying mechanism of resistance and the therapeutic potential of these molecules.

11.
Stroke Vasc Neurol ; 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35882433

RESUMO

BACKGROUND AND PURPOSE: C-C motif chemokine ligand 17 (CCL17) presents an important role in immune regulation, which is critical in the pathophysiology of brain injury after subarachnoid haemorrhage (SAH). There is rare evidence to illustrate the function of CCL17 towards SAH. In this study, we try to reveal the therapeutic effects of CCL17 and its underlying mechanism in rat SAH model. METHODS: SAH rat models were assigned to receive recombinant CCL17 (rCCL17) or phosphate buffer saline (PBS). AZD2098 and JR-AB2-011 were applied to investigate the C-C motif chemokine receptor 4 (CCR4)/mammalian target of rapamycin complex 2 (mTORC2) axis in CCL17-mediated neuroprotection. To elucidate the underlying mechanism, the in vitro kinase assay was performed in primary microglia. Microglial-specific Rictor knockdown was administered via intracerebroventricular injection of adenovirus-associated virus. Brain water content, short-term neurobehavioural evaluation, western blot analysis, quantitative RT-PCR and histological staining were performed. RESULTS: The expression of CCL17 was increased and secreted from neurons after oxyhaemoglobin stimulation. Exogenous rCCL17 significantly alleviated neuronal apoptosis, and alleviated short-term neurofunction after SAH in rats. In addition, rCCL17 increased M2-like polarisation of microglia in rats post-SAH and in primary microglia culture. The neuroprotection of rCCL17 was abolished via inhibition of either CCR4 or mTORC2. CONCLUSION: CCL17 activated the CCR4/mTORC2 axis in microglia, which can alleviate SAH-induced neurological deficits by promoting M2-like polarisation of microglia.

12.
Brief Bioinform ; 23(4)2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35788820

RESUMO

Complex biomedical data generated during clinical, omics and mechanism-based experiments have increasingly been exploited through cloud- and visualization-based data mining techniques. However, the scientific community still lacks an easy-to-use web service for the comprehensive visualization of biomedical data, particularly high-quality and publication-ready graphics that allow easy scaling and updatability according to user demands. Therefore, we propose a community-driven modern web service, Hiplot (https://hiplot.org), with concise and top-quality data visualization applications for the life sciences and biomedical fields. This web service permits users to conveniently and interactively complete a few specialized visualization tasks that previously could only be conducted by senior bioinformatics or biostatistics researchers. It covers most of the daily demands of biomedical researchers with its equipped 240+ biomedical data visualization functions, involving basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modelling, etc. Moreover, to improve the efficiency in use and development of plugins, we introduced some core advantages on the client-/server-side of the website, such as spreadsheet-based data importing, cross-platform command-line controller (Hctl), multi-user plumber workers, JavaScript Object Notation-based plugin system, easy data/parameters, results and errors reproduction and real-time updates mode. Meanwhile, using demo/real data sets and benchmark tests, we explored statistical parameters, cancer genomic landscapes, disease risk factors and the performance of website based on selected native plugins. The statistics of visits and user numbers could further reflect the potential impact of this web service on relevant fields. Thus, researchers devoted to life and data sciences would benefit from this emerging and free web service.


Assuntos
Software , Interface Usuário-Computador , Biologia Computacional/métodos , Visualização de Dados , Genômica , Humanos
13.
Nat Commun ; 13(1): 3301, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676256

RESUMO

Exercise benefits M2 macrophage polarization, energy homeostasis and protects against obesity partially through exercise-induced circulating factors. Here, by unbiased quantitative proteomics on serum samples from sedentary and exercised mice, we identify parvalbumin as a circulating factor suppressed by exercise. Parvalbumin functions as a non-competitive CSF1R antagonist to inhibit M2 macrophage activation and energy expenditure in adipose tissue. More importantly, serum concentrations of parvalbumin positively correlate with obesity in mouse and human, while treating mice with a recombinant parvalbumin blocker prevents its interaction with CSF1R and promotes M2 macrophage polarization and ameliorates diet-induced obesity. Thus, although further studies are required to assess the significance of parvalbumin in mediating the effects of exercise, our results implicate parvalbumin as a potential therapeutic strategy against obesity in mice.


Assuntos
Ativação de Macrófagos , Parvalbuminas , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica , Metabolismo Energético , Inflamação/metabolismo , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Parvalbuminas/metabolismo
14.
Front Pharmacol ; 13: 918531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712727

RESUMO

Post-stroke depression (PSD) is the most frequent and important neuropsychiatric consequence of stroke. It is strongly associated with exacerbated deterioration of functional recovery, physical and cognitive recoveries, and quality of life. However, its mechanism is remarkably complicated, including the neurotransmitters hypothesis (which consists of a monoaminergic hypothesis and glutamate-mediated excitotoxicity hypothesis), inflammation hypothesis, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophic hypothesis and neuroplasticity. So far, the underlying pathogenesis of PSD has not been clearly defined yet. At present, selective serotonin reuptake inhibitors (SSRIs) have been used as the first-line drugs to treat patients with PSD. Additionally, more than SSRIs, a majority of the current antidepressants complied with multiple side effects, which limits their clinical application. Currently, a wide variety of studies revealed the therapeutic potential of natural products in the management of several diseases, especially PSD, with minor side effects. Accordingly, in our present review, we aim to summarize the therapeutic targets of these compounds and their potential role in-clinic therapy for patients with PSD.

15.
Brain Sci ; 12(5)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35625048

RESUMO

(1) Background: glioma is the most prevalent primary tumor of the human central nervous system and accompanies extremely poor prognosis in patients. The transient receptor potential (TRP) channels family consists of six different families, which are closely associated with cancer cell proliferation, differentiation, migration, and invasion. TRP family genes play an essential role in the development of tumors. Nevertheless, the function of these genes in gliomas is not fully understood. (2) Methods: we analyze the gene expression data of 28 TRP family genes in glioma patients through bioinformatic analysis. (3) Results: the study showed the aberrations of TRP family genes were correlated to prognosis in glioma. Then, we set enrichment analysis and selected 10 hub genes that may play an important role in glioma. Meanwhile, the expression of 10 hub genes was further established according to different grades, survival time, IDH mutation status, and 1p/19q codeletion status. We found that TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, MCOLN1, MCOLN2, and MCOLN3 were significantly correlated to the prognosis in glioma patients. Furthermore, we illustrated that the expression of hub genes was associated with immune activation and immunoregulators (immunoinhibitors, immunostimulators, and MHC molecules) in glioma. (4) Conclusions: we proved that TRP family genes are promising immunotherapeutic targets and potential clinical biomarkers in patients with glioma.

16.
CNS Neurosci Ther ; 28(6): 942-952, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35290717

RESUMO

BACKGROUND: Despite having an overall benign course, non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH) is still accompanied by a risk of clinical complications and poor outcomes. Risk factors and mechanisms of complications and poor outcomes after naSAH remain unknown. Our aim was to explore the effect of stress-induced hyperglycemia (SIH) on complication rates and functional outcomes in naSAH patients. METHODS: We retrospectively reviewed patients with naSAH admitted to our institution between 2013 and 2018. SIH was identified according to previous criterion. Symptomatic vasospasm, delayed cerebral infarction, and hydrocephalus were identified as main complications. Outcomes were reviewed using a modified Rankin Scale (mRS) at discharge, 3 months, and 12 months. A statistical analysis was conducted to reveal the associations of SIH with complications and outcomes. RESULTS: A total of 244 naSAH patients were included in the cohort with 74 (30.3%) SIH. After adjusting for age, gender, hypertension, Hunt and Hess (HH) grade, modified Fisher Scale (mFS), intraventricular hemorrhage (IVH), and subarachnoid blood distribution, SIH was significantly associated with symptomatic vasospasm (p < 0.001, 12.176 [4.904-30.231]), delayed cerebral infarction (p < 0.001, 12.434 [3.850-40.161]), hydrocephalus (p = 0.008, 5.771 [1.570-21.222]), and poor outcome at 12 months (p = 0.006, 5.506 [1.632-18.581]), whereas the correlation between SIH and poor outcome at discharge (p = 0.064, 2.409 [0.951-6.100]) or 3 months (p = 0.110, 2.029 [0.852-4.833]) was not significant. Incorporation of SIH increased the area under curve (AUC) of ROC in the combined model for predicting symptomatic vasospasm (p = 0.002), delayed cerebral infarction (p = 0.024), hydrocephalus (p = 0.037), and 12-month poor outcome (p = 0.087). CONCLUSIONS: SIH is a significant and independent risk factor for symptomatic vasospasm, delayed cerebral infarction, hydrocephalus, and long-term poor outcome in naSAH patients. Identifying SIH early after naSAH is important for decision-making and treatment planning.


Assuntos
Hidrocefalia , Hiperglicemia , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Infarto Cerebral , Humanos , Hidrocefalia/etiologia , Hiperglicemia/complicações , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/terapia
17.
Cancer Immunol Immunother ; 71(3): 645-660, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34313821

RESUMO

PURPOSE: Glioma is the most common primary tumor in the brain, accounting for 81% of intracranial malignancies. Nowadays, cancer immunotherapy has become a novel and revolutionary treatment for patients with advanced, highly aggressive tumors. However, to date, there are no effective biomarkers to reflect the response of glioma patients to immunotherapy. In this study, we aimed to assess the clinical predictive value of ITGB2 in patients with glioma. METHODS: The correlation between ITGB2 expression levels and glioma progression was explored and validated using data from CGGA, TCGA, GEO datasets, and patient samples from our hospital. Univariate and multivariate cox regression models were developed to determine the predictive role of ITGB2 on the prognosis of patients with glioma. The relationship between ITGB2 and immune activation was then analyzed. Finally, we predicted the immunotherapy response in both high and low ITGB2 expression subgroups. RESULTS: ITGB2 was significantly elevated in gliomas with higher malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio for ITGB2 expression (low versus high) was 0.71 with 95% CI (0.59-0.85) (P < 0.001). Furthermore, we found that ITGB2 stratified glioma patients into high and low ITGB2 expression subgroups, exhibiting different clinical outcomes and immune activation status. At last, we demonstrated that glioma patients with high ITGB2 expression levels had better immunotherapy response. CONCLUSIONS: This study demonstrated ITGB2 as a novel predictor for clinical prognosis and response to immunotherapy in gliomas. Assessing expression levels of ITGB2 is a promising method to discover patients that may benefit from immunotherapy.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Glioma/diagnóstico , Glioma/metabolismo , Integrina beta1/metabolismo , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/terapia , Biologia Computacional/métodos , Bases de Dados Genéticas , Progressão da Doença , Perfilação da Expressão Gênica , Glioma/mortalidade , Glioma/terapia , Humanos , Integrina beta1/genética , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
18.
Curr Neuropharmacol ; 20(6): 1194-1211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34766893

RESUMO

The caspase family is commonly involved in the pathophysiology of acute brain injury (ABI) through complex apoptotic, pyroptotic, and inflammatory pathways. Current translational strategies for caspase modulation in ABI primarily focus on caspase inhibitors. Because there are no caspase-inhibiting drugs approved for clinical use on the market, the development of caspase inhibitors remains an attractive challenge for researchers and clinicians. Therefore, we conducted the present review with the aim of providing a comprehensive introduction of caspases in ABI. In this review, we summarized the available evidence and potential mechanisms regarding the biological function of caspases. We also reviewed the therapeutic effects of caspase inhibitors on ABI and its subsequent complications. However, various important issues remain unclear, prompting further verification of the efficacy and safety regarding clinical application of caspase inhibitors. We believe that our work will be helpful to further understand the critical role of the caspase family and will provide novel therapeutic potential for ABI treatment.


Assuntos
Lesões Encefálicas , Caspases , Apoptose/fisiologia , Lesões Encefálicas/tratamento farmacológico , Inibidores de Caspase/farmacologia , Inibidores de Caspase/uso terapêutico , Caspases/metabolismo , Caspases/farmacologia , Humanos
19.
CNS Neurosci Ther ; 27(10): 1238-1250, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34268874

RESUMO

AIM: To demonstrate the clinical value of epithelial membrane protein 3 (EMP3) with bioinformatic analysis and clinical data, and then to establish a practical nomogram predictive model with bicenter validation. METHODS: The data from CGGA and TCGA database were used to analyze the expression of EMP3 and its correlation with clinical prognosis. Then, we analyzed EMP3 expression in samples from 179 glioma patients from 2013 to 2017. Univariate and multivariate cox regression were used to predict the prognosis with multiple factors. Finally, a nomogram to predict poor outcomes was formulated. The accuracy and discrimination of nomograms were determined with ROC curve and calibration curve in training and validation cohorts. RESULTS: EMP3 was significantly higher in higher-grade glioma and predicted poor prognosis. In multivariate analysis, high expression of EMP3 (HR = 2.842, 95% CI 1.984-4.071), WHO grade (HR = 1.991, 95% CI 1.235-3.212), and IDH1 mutant (HR = 0.503, 95% CI 0.344-0.737) were included. The nomogram was constructed based on the above features, which represented great predictive value in clinical outcomes. CONCLUSION: This study demonstrated EMP3 as a novel predictor for clinical progression and clinical outcomes in glioma. Moreover, the nomogram with EMP3 expression represented a practical approach to provide individualized risk assessment for glioma patients.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioma/genética , Glioma/terapia , Glicoproteínas de Membrana/genética , Nomogramas , Adulto , Idoso , Algoritmos , Biomarcadores Tumorais , Bases de Dados Genéticas , Feminino , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
20.
iScience ; 24(6): 102668, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34142068

RESUMO

[This retracts the article DOI: 10.1016/j.isci.2020.101845.].

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