Research Progress in the Field of Tumor Model Construction Using Bioprinting: A Review.

The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.

SP1-Driven FOXM1 Upregulation Induces Dopaminergic Neuron Injury in Parkinson's Disease.

The aberrant expression of Forkhead box M1 (FOXM1) has been associated with the pathological processes of Parkinson's disease (PD), but the upstream and downstream regulators remain poorly understood. This study sought to examine the underlying mechanism of FOXM1 in dopaminergic neuron injury in PD. Bioinformatics analysis was conducted to pinpoint the differential expression of FOXM1, which was verified in the nigral tissues of rotenone-lesioned mice and dopaminergic neuron MN9D cells. Interactions among SP1, FOXM1, SNAI2, and CXCL12 were analyzed. To evaluate their effects on dopaminergic neuron injury, the lentiviral vector-mediated manipulation of FOXM1, SP1, and CXCL12 was introduced in rotenone-lesioned mice and MN9D cells. SP1, FOXM1, SNAI2, and CXCL12 abundant expression occurred in rotenone-lesioned mice and MN9D cells. Silencing of FOXM1 delayed the rotenone-induced dopaminergic neuron injury in vitro. Mechanistically, SP1 was an upstream transcription factor of FOXM1 and upregulated FOXM1 expression, leading to increased SNAI2 and CXCL12 expression. In vivo, data confirmed that SP1 promoted dopaminergic neuron injury by activating the FOXM1/SNAI2/CXCL12 axis. Our data indicate that SP1 silencing has neuroprotective effects on dopaminergic neurons, which is dependent upon the inactivated FOXM1/SNAI2/CXCL12 axis.

Association between High-Sensitivity C-Reactive Protein and Blood Pressure Variability in Subacute Stage of Ischemic Stroke.

The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations.

JMJD3 and SNAI2 synergistically protect against Parkinson's disease by mediating the YAP/HIF1α signaling pathway in a mouse model.

This study aimed to characterize the functional relevance and mechanistic basis of the histone demethylase Jumonji domain-containing protein-3 (JMJD3) in preserving dopaminergic neuron survival in Parkinson's disease (PD). Mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced lesions and MN9D dopaminergic neuronal cell lines exposed to 6-OHDA, respectively, were used to simulate in vivo and in vitro PD-like environments. PD-related genes with differential expressions were identified using RNA sequencing of hippocampal tissues collected from MPTP-lesioned mice. A specific lentiviral shRNA vector was used to investigate the effects of JMJD3 on neuron activities in vitro and PD-like phenotypes in vivo. JMJD3 was found to up-regulate the expression of Snail family transcriptional repressor 2 (SNAI2) through the inhibition of H3 on lysine 27 (H3K27me3) enrichment in the SNAI2 promoter region. As a result, the viability of 6-OHDA-exposed MN9D cells was stimulated, and cell apoptosis was diminished. Knockdown of SNAI2 decreased the expression of yes-associated protein (YAP) and HIF1α while also reducing the viability of 6-OHDA-exposed MN9D cells and increasing cell apoptosis. The in vivo experiments demonstrated that JMJD3 activated the SNAI2/YAP/HIF1α signaling pathway, inhibiting PD-like phenotypes in MPTP-lesioned mice. Thus, the findings provide evidence that JMJD3 inhibits the enrichment of H3K27me3 at the SNAI2 promoter, leading to the upregulation of SNAI2 expression and activation of the YAP/HIF1α signaling pathway, ultimately exerting a protective effect on PD mice. This finding suggests that targeting the JMJD3-SNAI2 pathway could be a promising therapeutic strategy for PD. Further in-depth studies are needed to elucidate the underlying mechanisms and identify potential downstream targets of this pathway.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

Smart nanogels for cancer treatment from the perspective of functional groups.

Introduction: Cancer remains a significant health challenge, with chemotherapy being a critical treatment modality. However, traditional chemotherapy faces limitations due to non-specificity and toxicity. Nanogels, as advanced drug carriers, offer potential for targeted and controlled drug release, improving therapeutic efficacy and reducing side effects. Methods: This review summarizes the latest developments in nanogel-based chemotherapy drug delivery systems, focusing on the role of functional groups in drug loading and the design of smart hydrogels with controlled release mechanisms. We discuss the preparation methods of various nanogels based on different functional groups and their application in cancer treatment. Results: Nanogels composed of natural and synthetic polymers, such as chitosan, alginate, and polyacrylic acid, have been developed for chemotherapy drug delivery. Functional groups like carboxyl, disulfide, and hydroxyl groups play crucial roles in drug encapsulation and release. Smart hydrogels have been engineered to respond to tumor microenvironmental cues, such as pH, redox potential, temperature, and external stimuli like light and ultrasound, enabling targeted drug release. Discussion: The use of functional groups in nanogel preparation allows for the creation of multifunctional nanogels with high drug loading capacity, controllable release, and good targeting. These nanogels have shown promising results in preclinical studies, with enhanced antitumor effects and reduced systemic toxicity compared to traditional chemotherapy. Conclusion: The development of smart nanogels with functional group-mediated drug delivery and controlled release strategies represents a promising direction in cancer therapy. These systems offer the potential for improved patient outcomes by enhancing drug targeting and minimizing adverse effects. Further research is needed to optimize nanogel design, evaluate their safety and efficacy in clinical trials, and explore their potential for personalized medicine.

Long Non-coding RNA HOTAIR in Central Nervous System Disorders: New Insights in Pathogenesis, Diagnosis, and Therapeutic Potential.

Central nervous system (CNS) disorders, such as ischemic stroke, neurodegenerative diseases, multiple sclerosis, traumatic brain injury, and corresponding neuropathological changes, often lead to death or long-term disability. Long non-coding RNA (lncRNA) is a class of non-coding RNA with a transcription length over 200 nt and transcriptional regulation. lncRNA is extensively involved in physiological and pathological processes through epigenetic, transcription, and post-transcriptional regulation. Further, dysregulated lncRNA is closely related to the occurrence and development of human diseases, including CNS disorders. HOX Transcript antisense RNA (HOTAIR) is the first discovered lncRNA with trans-transcriptional regulation. Recent studies have shown that HOTAIR may participate in the regulation of the occurrence and development of CNS disorders. In addition, HOTAIR has the potential to become a new biomarker for the diagnosis and prognosis assessment of CNS disorders and even provide a new therapeutic target for CNS disorders. Here, we reviewed the research results of HOTAIR in CNS disorders to provide new insights into the pathogenesis, diagnostic value, and therapeutic target potential of HOTAIR in human CNS disorders.

Lipid-lowering treatment in a rabbit model of atherosclerosis: a vessel wall magnetic resonance imaging study.

Background: Vessel wall magnetic resonance imaging (VWMRI) is currently one of the best imaging techniques for the non-invasive evaluation of intracranial atherosclerotic lesions. However, it is still impossible to obtain pathological specimens of intracranial atherosclerotic plaques in vivo. The establishment of experimental animal models of atherosclerotic lesions similar to those of humans could solve this deficiency. Methods: A model of abdominal aortic atherosclerosis in New Zealand white rabbits was established using abdominal aortic balloon dilatation combined with high-fat fodder. The pathological results were used as the reference standard for the successful establishment of the animal model. The rabbits with abdominal aortic atherosclerosis were randomly divided into the lipid-lowering treatment and the normal-fodder control groups. VWMRI and blood biochemical examinations were performed at 4, 12, and 24 weeks, and the radiologic-pathologic correlations were established. Results: A rabbit abdominal aortic atherosclerosis model was established using balloon dilatation followed by high-fat fodder for 8 weeks. The lipid-lowering treatment reduced the plaque lipid core volume and decreased the plaque burden. However, it did not change plaque distribution, shape, or reverse vascular remodeling. Our pathological findings suggest that the lipid-lowering treatment reduced intraplaque macrophages but did not alter microvascular density. Conclusions: VWMRI accurately assessed the morphological changes of the plaques before and after the lipid-lowering treatment, and the results support the pathology results. VWMRI could be useful in experimental studies on the pathogenesis, diagnosis, and treatment of atherosclerotic lesions.

Crosstalk between peripheral and the brain-resident immune components in epilepsy.

Epilepsy is one of the most common neurology diseases. It is characterized by recurrent, spontaneous seizures and accompanied by various comorbidities which can significantly affect a person's life. Accumulating evidence indicates an essential pathophysiological role for neuroinflammation in epilepsy, which involves activation of microglia and astrocytes, recruitment of peripheral leukocytes into the central nervous system, and release of some inflammatory mediators, including pro-inflammatory factors and anti-inflammatory cytokines. There is complex crosstalk between the central nervous system and peripheral immune responses associated with the progression of epilepsy. This review provides an update of current knowledge about the contribution of this crosstalk associated with epilepsy. Additionally, how gut microbiota is involved in epilepsy and its possible influence on crosstalk is also discussed. Such recent advances in understanding suggest innovative methods for targeting the molecules correlated with the crosstalk and may provide a better prognosis for patients diagnosed with epilepsy.

lncRNA NEAT1 prompts autophagy and apoptosis in MPTP-induced Parkinson's disease by impairing miR-374c-5p.

Long non-coding RNAs (lncRNAs) play biological roles in brain disorder and neurodegenerative diseases. As the functions of lncRNA NEAT1 in Parkinson's disease (PD) remain unknown, in the present study, we aimed to explore the roles and underlying molecular mechanisms of NEAT1 in PD. A PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and a cell model of SH-SY5Y induced by N-methyl-4-phenylpyridinium (MPP+) were established. The ratio of tyrosine hydroxylase (TH+) cells was determined by immunofluorescence assay, and the behavioral changes in mice were observed using pole tests and rotarod tests. The cellular viability and apoptosis of SH-SY5Y were detected by MTT assay and flow cytometric analysis, respectively, and the number of autophagosomes was subsequently measured by transmission electron microscopy. High-performance liquid chromatography was performed to detect the content of dopamine, and a dual-luciferase reporter assay was used to clarify the target of NEAT1 simultaneously. The results demonstrated that the level of NEAT1 was upregulated in the MPTP-induced PD mice, dopamine neurons, and the SH-SY5Y cells treated with MPP+, whereas the level of miR-374c-5p was downregulated. NEAT1 level was positively correlated with MPP+ in a concentration-dependent manner. NEAT1 inhibition efficiently facilitated cell proliferation but inhibited apoptosis and autophagy in the MPP+-treated SH-SY5Y cells. Additionally, silencing of NEAT1 increased the TH+ rate of neurons and suppressed autophagy greatly in PD mice. As a possible target of NEAT1, miR-374c-5p could impact on the apoptosis and autophagy of the SH-SY5Y cells. NEAT1 inhibition upregulated the expression of miR-374c-5p, enhanced SH-SY5Y cell viability, and repressed autophagy and apoptosis in MPTP-induced PD mice. These findings indicated a potential therapeutic role of NEAT1 in treating PD.

Red-light is an environmental effector for mutualism between begomovirus and its vector whitefly.

Environments such as light condition influence the spread of infectious diseases by affecting insect vector behavior. However, whether and how light affects the host defense which further affects insect preference and performance, remains unclear, nor has been demonstrated how pathogens co-adapt light condition to facilitate vector transmission. We previously showed that begomoviral ßC1 inhibits MYC2-mediated jasmonate signaling to establish plant-dependent mutualism with its insect vector. Here we show red-light as an environmental catalyzer to promote mutualism of whitefly-begomovirus by stabilizing ßC1, which interacts with PHYTOCHROME-INTERACTING FACTORS (PIFs) transcription factors. PIFs positively control plant defenses against whitefly by directly binding to the promoter of terpene synthase genes and promoting their transcription. Moreover, PIFs interact with MYC2 to integrate light and jasmonate signaling and regulate the transcription of terpene synthase genes. However, begomovirus encoded ßC1 inhibits PIFs' and MYC2' transcriptional activity via disturbing their dimerization, thereby impairing plant defenses against whitefly-transmitted begomoviruses. Our results thus describe how a viral pathogen hijacks host external and internal signaling to enhance the mutualistic relationship with its insect vector.

Balloon-mounted stenting for ICAS in a multicenter registry study in China: a comparison with the WEAVE/WOVEN trial.

BACKGROUND: The outcome of deploying balloon-mounted stents for symptomatic intracranial atherosclerotic stenosis (ICAS) has not been fully investigated. In this study we evaluate the safety and long-term outcome of using balloon-mounted stents to treat symptomatic ICAS in comparison with the WEAVE/WOVEN study. METHODS: In a multicenter registry study of stenting for symptomatic intracranial artery stenosis in China, 159 patients treated with an intracranial balloon-mounted stent approved by the China Food and Drug Administration were evaluated. The morphological features of the lesions were categorized by Mori classification. The endpoints, including periprocedural and long-term clinical and radiological outcomes, were the same as those in the WEAVE/WOVEN study. RESULTS: In the present study the mean percent stenosis before and after stenting was 84.0% and 6.1%, respectively. The proportions of Mori A, Mori B, and Mori C lesions were 33.3%, 52.2%, and 14.5%, respectively. The 72-hour rates of stroke and mortality after the procedure were 0%. The 1-year rates of any stroke, ischemic stroke, hemorrhagic stroke, and death were 6.3% (10/159), 5.7% (9/159), 0.6% (1/159), and 0.6% (1/159), respectively. The 1-year rate of in-stent restenosis (ISR) was 23.4% (15/64). The rate of ISR in Mori C lesions (53.8%, 7/13) was significantly higher than that in Mori A (15.8%, 3/19) or Mori B lesions (15.6%, 5/32) (p=0.024). CONCLUSIONS: The short-term and long-term outcomes of using a balloon-mounted stent for symptomatic ICAS with focal and non-angular lesions (Mori A and B type) and smooth arterial access were comparable to the results of the WEAVE/WOVEN trial.

Safety and Efficacy of Tirofiban in Acute Ischemic Stroke Patients Receiving Endovascular Treatment: A Meta-Analysis.

OBJECTIVES: Tirofiban is widely used in clinical practice for acute ischemic stroke (AIS). However, whether tirofiban increases the bleeding risk or improves the outcome of AIS patients with endovascular treatment (ET) is unknown. The aim of this meta-analysis is to evaluate the safety and efficacy of tirofiban compared with those without tirofiban in AIS patients receiving ET. METHODS: Systematic literature search was done in PubMed and EMBASE databases without language or time limitation. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes were recanalization rate and favorable functional outcome. Review Manager 5.3 and Stata Software Package 15.0 were used to perform the meta-analysis. RESULTS: Eleven studies with a total of 2,028 patients were included. A total of 704 (34.7%) patients were administrated tirofiban combined with ET. Meta-analysis suggested that tirofiban did not increase the risk of sICH (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81-1.46; p = 0.59) but significantly decreased mortality (OR 0.68; 95% CI 0.52-0.89; p = 0.005). There was no association between tirofiban and recanalization rate (OR 1.26; 95% CI 0.86-1.82; p = 0.23) or favorable functional outcome (OR 1.21; 95% CI 0.88-1.68; p = 0.24). Subgroup analyses indicated that preoperative tirofiban significantly increase recanalization rate (OR 3.89; 95% CI 1.70-8.93; p = 0.001) and improve favorable functional outcome (OR 2.30; 95% CI 1.15-4.60; p = 0.02). CONCLUSIONS: Tirofiban is safe in AIS patients with ET and can significantly reduce mortality; preoperative tirofiban may be effective, but further studies are needed to confirm the efficacy.

Stenting for symptomatic intracranial arterial stenosis in China: 1-year outcome of a multicentre registry study.

Background and purpose: A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis (ICAS) combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable. However, it remained uncertain whether the low event rate could be of a long term. We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals. Methods: Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid, middle cerebral, intracranial vertebral or basilar arteries combined with poor collaterals were enrolled. Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators. The primary outcome was the rate of 30-day stroke, transient ischaemic attack and death, and 12-month ischaemic stroke within the same vascular territory, haemorrhagic stroke and vascular death after stenting. Results: From September 2013 to January 2015, 300 patients (ages 58.3±9.78 years) were recruited. Among them, 159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent. During the 1-year follow-up, 25 patients had a primary end point event. The probability of primary outcome at 1 year was 8.1% (95% CI 5.3% to 11.7%). In 76 patients with digital subtraction angiography follow-up, 27.6% (21/76) had re-stenosis ≥50% and 18.4% (14/76) had re-stenosis ≥70%. No baseline characteristic was associated with the primary outcome. Conclusion: The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals. Further randomised trial of comparing individually tailored stenting with best medical therapy is needed. Trial registration number: NCT01968122; Results.

Thirty-Day Outcome of a Multicenter Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China.

BACKGROUND AND PURPOSE: Although recent trials have suggested that stenting is worse than medical therapy for patients with severe symptomatic intracranial atherosclerotic stenosis, it is not clear whether this conclusion applies to a subset of patients with hypoperfusion symptoms. To justify for a new trial in China, we performed a multicenter prospective registry study to evaluate the safety and efficacy of endovascular stenting within 30 days for patients with severe symptomatic intracranial atherosclerotic stenosis. METHODS: Patients with symptomatic intracranial atherosclerotic stenosis caused by 70% to 99% stenosis combined with poor collaterals were enrolled. The patients were treated either with balloon-mounted stent or with balloon predilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome within 30 days is stroke, transient ischemic attack, and death after stenting. The secondary outcome is successful revascularization. The baseline characteristics and outcomes of the 2 treatment groups were compared. RESULTS: From September 2013 to January 2015, among 354 consecutive patients, 300 patients (aged 58.3±9.78 years) were recruited, including 159 patients treated with balloon-mounted stent and 141 patients with balloon plus self-expanding stent. The 30-day rate of stroke, transient ischemic attack, and death was 4.3%. Successful revascularization was 97.3%. Patients treated with balloon-mounted stent were older, less likely to have middle cerebral artery lesions, more likely to have vertebral artery lesions, more likely to have Mori A lesions, less likely to have Mori C lesions, and likely to have lower degree of residual stenosis than patients treated with balloon plus self-expanding stent. CONCLUSIONS: The short-term safety and efficacy of endovascular stenting for patients with severe symptomatic intracranial atherosclerotic stenosis in China is acceptable. Balloon-mounted stent may have lower degree of residual stenosis than self-expanding stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.

Association between 5-HTTLPR polymorphism and Parkinson's disease: a meta analysis.

To investigate the genetic association of 5-HTTLPR polymorphism and Parkinson's disease (PD) or depression in PD by using meta analysis. Published association studies on genotype or allele frequencies of the 5-HTTLPR in patients with or without PD or in PD patients with or without depression in all ethnic groups were included. A biallelic meta-analysis, including biallelic frequency model, biallelic dominant model (BDM) and biallelic recessive model, was performed using the Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio and its corresponding 95 % CI with a random-effect model. Six studies met the criteria for the meta-analysis of association of 5-HTTLPR and three studies were included for the association of 5-HTTLPR and depression in PD. The meta-analysis results did not show significant association between 5-HTTLPR and PD or depression in PD, except for a moderate negative association between 5-HTTLPR and PD in Asian subgroup (2 studies) using the BDM approach. Our meta-analysis result does not support a direct primary effect of 5-HTTLPR on PD or depression in PD. Further association studies with larger sample sizes preferably taking into consideration factors such as additional allelic variants in the 5-HTTLPR, ethnic variation of the 5-HTTLPR distribution and gene-gene interaction are necessary to reach a more definite conclusion.

Correlations of MCP-1 -2518A>G polymorphism and serum levels with cerebral infarction risk: a meta-analysis.

This meta-analysis was performed to evaluate the relationships between the monocyte chemoattractant protein-1 (MCP-1) -2518A>G (rs1024611 A>G) polymorphism and its serum levels, and the risk of cerebral infarction. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1st, 2013 without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) or standardized mean difference (SMD) with their 95% confidence intervals (95% CIs) were calculated. Twelve case-control studies that met all the inclusion criteria were included in this meta-analysis. A total of 1272 patients with cerebral infarction and 1210 healthy control subjects were involved in this meta-analysis. Our meta-analysis results reveal that the MCP-1 -2518A>G polymorphism might increase the risk of cerebral infarction (A allele vs. G allele: OR=1.37, 95% CI: 1.18-1.60, p<0.001; GA+AA vs. GG: OR=1.33, 95% CI: 1.09-1.62, p=0.005; respectively). Furthermore, cerebral infarction patients had higher levels of serum MCP-1 than did healthy control subjects (SMD=2.96, 95% CI: 2.00-3.92, p<0.001). Statistical analysis revealed no evidence of publication bias in this meta-analysis (all p>0.05). Our findings indicate that the MCP-1 -2518A>G polymorphism and serum MCP-1 levels may contribute to the development of cerebral infarction. Thus, the MCP-1 -2518A>G polymorphism and serum MCP-1 levels could be potential biomarkers for the early detection of cerebral infarction.

Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is affecting 5 million people worldwide, but the response mechanisms of the striatum are still unclear. Therefore, identification of gene expression alterations in the striatum will greatly assist the development of novel therapy strategies. METHODS: We performed a comprehensive gene expression analysis in 15 PD patients and 15 normal controls to identify differentially expressed genes (DEGs) using the expression profile GSE20291 from Gene Expression Omnibus (GEO). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were used to define functions and pathways altered in PD. Protein-protein interaction network was constructed to find out the modules with close interactions. RESULTS: Total715 DEGs including 268 up-regulated and 447 down-regulated genes were obtained. GO functional enrichment analysis indicated that the genes related with neurons function and cell morphogenesis might be changed upon PD. KEGG pathway enrichment analysis showed that most of the genes were enriched in the nodes of Gap junction, calcium signaling pathway, phosphatidylinositol signaling system, long-term potentiation, Alzheimer's disease and GnRH signaling pathway. Protein-protein interaction network and module analysis suggested that some apoptosis related genes, such as PRKCA, CDC42 and BCL2 may play critical roles in striatal neurons growth. CONCLUSION: Intrinsic striatal tyrosine hydroxylase interneurons growth may be promoted by changes in several genes expression and thus reduce the functional excitatory synapses.