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Brain and Behavior Feb 2023Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment... (Review)
Review
BACKGROUND
Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment is relatively scarce. Hyperalgesia mediated by pro-inflammatory factors and chemokines plays an important role in the occurrence and maintenance of NP.
DATA TREATMENT
Therefore, we conducted a systematic literature review of experimental NP (PubMed Medline), in order to find the mechanism of inducing central sensitization and explore the intervention methods of hyperalgesia caused by real or simulated injury.
RESULT
In this review, we sorted out the activation pathways of microglia, astrocytes and neurons, and the process of crosstalk among them. It was found that in NP, the microglia P2X4 receptor is the key target, which can activate the mitogen-activated protein kinase pathway inward and then activate astrocytes and outwardly activate neuronal tropomyosin receptor kinase B receptor to activate neurons. At the same time, activated neurons continue to maintain the activation of astrocytes and microglia through chemokines on CXCL13/CXCR5 and CX3CL1/CX3CR1. This crosstalk process is the key to maintaining NP.
CONCLUSION
We summarize the further research on crosstalk among neurons, microglia, and astrocytes in the central nervous system, elaborate the ways and connections of relevant crosstalk, and find potential crosstalk targets, which provides a reference for drug development and preclinical research.
Topics: Humans; Hyperalgesia; Neuroglia; Neuralgia; Neurons; Spinal Cord; Microglia; Astrocytes
PubMed: 36602945
DOI: 10.1002/brb3.2868 -
Cancer Metastasis Reviews Mar 2022Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine... (Review)
Review
BACKGROUND
Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.
METHODS
Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.
RESULTS
Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.
CONCLUSIONS
Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.
Topics: Carcinogenesis; Cell Line, Tumor; Child; Humans; Neuroblastoma; Receptor Protein-Tyrosine Kinases; Signal Transduction
PubMed: 34716856
DOI: 10.1007/s10555-021-10001-7 -
BMC Cancer Oct 2023N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.
METHODS
The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.
RESULTS
A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13-1.05, I: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32-(-0.20), I: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).
CONCLUSION
The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.
Topics: Female; Humans; Axilla; Breast Neoplasms; Cell Cycle Proteins; Intracellular Signaling Peptides and Proteins; Lymph Nodes; Receptor, ErbB-2; Receptors, Progesterone
PubMed: 37858101
DOI: 10.1186/s12885-023-11517-7 -
Archives of Gerontology and Geriatrics Nov 2023Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Debates persist regarding the performance of existing glomerular filtration rate (GFR) estimating equations in older individuals. We performed this meta-analysis to assess the accuracy and bias of six commonly used equations, including the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI) and its combination with cystatin C (CKD-EPI), with the corresponding pair of the Berlin Initiative Study equations (BIS1 and BIS2) and the Full Age Spectrum equations (FAS and FAS).
METHODS
PubMed and the Cochrane Library were searched for studies comparing estimated GFR (eGFR) with measured GFR (mGFR). We analyzed the difference in P30 and bias among the six equations and investigated subgroups based on the area (Asian and non-Asian), mean age (60-74 years and ≥75 years), and levels of mean mGFR (<45 mL/min/1.73m and ≥45 mL/min/1.73m).
RESULTS
27 studies with 18,112 participants were included, all reporting P30 and bias. BIS1 and FAS exhibited significantly higher P30 than CKD-EPI. While no significant differences were observed between FAS and BIS1, or among the three combined equations in terms of either P30 or bias. Subgroup analyses revealed FAS and FAS achieved better results in most situations. However, in the subgroup of mGFR<45 mL/min/1.73m, CKD-EPI had relatively higher P30 and significantly smaller bias.
CONCLUSIONS
Overall, BIS and FAS provided relatively more accurate estimates of GFR than CKD-EPI in older adults. FAS and FAS may be better suited for various conditions, while CKD-EPI would be a better option for older individuals with impaired renal function.
Topics: Aged; Humans; Asian; Creatinine; ErbB Receptors; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Middle Aged; Reproducibility of Results; Models, Biological
PubMed: 37379796
DOI: 10.1016/j.archger.2023.105107 -
Translational Neurodegeneration Apr 2022A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson's disease (PD) to the development of sleep disturbance in PD and... (Meta-Analysis)
Meta-Analysis Review
A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson's disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, including 17 studies on glucocerebrosidase (GBA), 25 studies on Leucine-rich repeat kinase 2 (LRRK2) and 7 on parkin (PRKN) genes, and 3 studies on alpha-synuclein gene (SNCA) were used for qualitative analysis. Patients with PD carrying GBA variants had a significantly higher risk for rapid-eye-movement behavior disorders (RBD) (OR, 1.82) and higher RBD Screening Questionnaire scores (SMD, 0.33). Asymptomatic carriers of GBA variants had higher severity of RBD during follow-up. Patients with PD carrying the LRRK2 G2019S variant had lower risk and severity of RBD compared with those without LRRK2 G2019S. Variants of GBA, LRRK2 and PRKN did not increase or decrease the risk and severity of excessive daytime sleepiness and restless legs syndrome in PD. Our findings suggest that the genetic heterogeneity plays a role in the development of sleep disorders, mainly RBD, in PD and the prodromal stage of PD.
Topics: Genetic Heterogeneity; Glucosylceramidase; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mutation; Parkinson Disease; Prodromal Symptoms; Sleep Wake Disorders; alpha-Synuclein
PubMed: 35395825
DOI: 10.1186/s40035-022-00294-1 -
The Journal of Maternal-fetal &... Jun 2020Multiple factors and pathways have been reported as critical machineries for cell differentiation and survival during pregnancy; a number of them involve glycogen...
Multiple factors and pathways have been reported as critical machineries for cell differentiation and survival during pregnancy; a number of them involve glycogen synthase kinase (GSK) 3a/β. Several reports on GSK3's functional role exist; however, the specific role of GSK3 in reproductive tissues and its contribution to normal or abnormal parturition are still unclear. To fill this knowledge gap, a systematic review of literature was conducted to better understand the functional role of GSK3 in various intrauterine tissues during implantation, pregnancy, and parturition. We conducted a systematic review of literature on GSK3's expression and function reported between 1980 and 2017 in reproductive tissues during pregnancy using three electronic databases (Web of Science, Medline, and ClinicalTrials.gov). Study selection, data extraction, quality assessment and analyses were performed in duplicate by two independent reviewers. A total of 738 citations were identified; 80 were selected for full text evaluation and 25 were included for final review. GSK3's regulation and function were mostly studied in tissues and cells from placentas (12), fetuses (8), uteruses (6), and ovaries (2). GSK3 is primarily reported as a downstream responder of protein kinase B (AKT)-, Wnt-, and reactive oxygen species (ROS)-related pathways where it plays a critical role in cell survival and growth in reproductive tissues. Though GSK3 has been functionally linked to a number of biological processes in reproductive tissues, it has primarily been studied as a secondary signaler of various conserved cell signaling pathways. Lack of scientific rigor in studying GSK3's role in reproductive tissues makes this molecule's function still obscure. No studies have reported GSK3 in the cervix, and very few reports exist in myometrium and decidua. This systematic review suggests more functional and mechanistic studies focusing on GSK3 need to be conducted in reproductive biology.
Topics: Biomarkers; Female; Glycogen Synthase Kinase 3; Humans; Parturition; Pregnancy
PubMed: 30278798
DOI: 10.1080/14767058.2018.1531843 -
International Journal of Molecular... Jul 2023The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal... (Meta-Analysis)
Meta-Analysis
Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression ( < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; ErbB Receptors; Head and Neck Neoplasms; Biomarkers, Tumor
PubMed: 37569265
DOI: 10.3390/ijms241511888 -
European Journal of Clinical Nutrition Aug 2023It is unknown whether dietary protein consumption can attenuate resistance exercise-induced muscle damage (EIMD). Managing EIMD may accelerate muscle recovery and allow... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is unknown whether dietary protein consumption can attenuate resistance exercise-induced muscle damage (EIMD). Managing EIMD may accelerate muscle recovery and allow frequent, high-quality exercise to promote muscle adaptations. This systematic review and meta-analysis examined the impact of peri-exercise protein supplementation on resistance EIMD.
METHODS
A literature search was conducted on PubMed, SPORTDiscus, and Web of Science up to March 2021 for relevant articles. PEDro criteria were used to assess bias within included studies. A Hedges' g effect size (ES) was calculated for indirect markers of EIMD at h post-exercise. Weighted ESs were included in a random effects model to determine overall ESs over time.
RESULTS
Twenty-nine studies were included in the systematic review and 40 trials were included in ≥1 meta-analyses (16 total). There were significant overall effects of protein for preserving isometric maximal voluntary contraction (MVC) at 96 h (0.563 [0.232, 0.894]) and isokinetic MVC at 24 h (0.639 [0.116, 1.162]), 48 h (0.447 [0.104, 0.790]), and 72 h (0.569 [0.136, 1.002]). Overall ESs were large in favour of protein for attenuating creatine kinase concentration at 48 h (0.836 [-0.001, 1.673]) and 72 h (1.335 [0.294, 2.376]). Protein supplementation had no effect on muscle soreness compared with the control.
CONCLUSION
Peri-exercise protein consumption could help maintain maximal strength and lower creatine kinase concentration following resistance exercise but not reduce muscle soreness. Conflicting data may be due to methodological divergencies between studies. Standardised methods and data reporting for EIMD research are needed.
Topics: Humans; Myalgia; Muscle, Skeletal; Resistance Training; Dietary Proteins; Dietary Supplements; Creatine Kinase
PubMed: 36513777
DOI: 10.1038/s41430-022-01250-y -
Scientific Reports Jun 2023Many studies report Liver kinase B1 (LKB1) plays a critical role in gastric cancer (GC). However, the relationship between LKB1 and the clinicopathological parameters of... (Meta-Analysis)
Meta-Analysis
Many studies report Liver kinase B1 (LKB1) plays a critical role in gastric cancer (GC). However, the relationship between LKB1 and the clinicopathological parameters of GC patients remains controversial. This meta-analysis aimed to investigate the above question and re-evaluate the prognostic significance of LKB1 in GC patients. We searched PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, and Wan Fang to identify relevant studies published before April 20, 2023. After careful screening, 11 studies involving 1767 patients were included. We found that LKB1 expression was significantly related to tumor size (OR 0.515; 95% CI 0.316-0.839; P < 0.01), differentiation (OR 0.643; 95% CI 0.521-0.794; P < 0.001), depth of invasion (OR 0.397; 95% CI 0.319-0.494; P < 0.001), lymph node metastasis (OR 0.487; 95% CI 0.397-0.598; P = 0.01), and TNM stage (OR 0.362; 95% CI 0.293-0.447; P = 0.006). However, LKB1 was unrelated to gender and age (P > 0.05). Moreover, low LKB1 expression was significant correlate with overall survival (OS) (HR = 1.59; 95% CI 1.29-1.96; P < 0.001). In conclusion, LKB1 expression is related to tumor size, differentiation, depth of invasion, lymph node metastasis, and TNM stage, and low LKB1 expression can predict a poor prognosis. LKB1 is a potentially valuable prognosis signature and therapeutic target in GC patients.
Topics: Humans; Biomarkers, Tumor; Lymphatic Metastasis; Prognosis; Protein Serine-Threonine Kinases; Stomach Neoplasms
PubMed: 37264076
DOI: 10.1038/s41598-023-36239-5 -
ESMO Open Jun 2022Brain metastases (BMs) are frequent events in patients with HER2-positive metastatic breast cancer (MBC) and are associated with poor prognosis. Small-molecule anti-HER2... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Brain metastases (BMs) are frequent events in patients with HER2-positive metastatic breast cancer (MBC) and are associated with poor prognosis. Small-molecule anti-HER2 tyrosine kinase inhibitors (TKIs) are promising agents for the treatment of BM. In this study, we assess the clinical outcomes of patients with HER2-positive MBC and BM treated with TKI-containing regimens compared with those treated with non-TKI-containing regimens.
MATERIALS AND METHODS
PubMed, Embase, Cochrane Library, and conference proceedings (ASCO, SABCS, ESMO, and ESMO Breast) were searched up to June 2021. The primary endpoint was progression-free survival (PFS) in patients with BM. Secondary endpoints included PFS in patients without BM and overall survival (OS). The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models.
RESULTS
This systematic review and meta-analysis included data from 2437 patients (490 with and 1947 without BM at baseline) enrolled in five trials assessing tucatinib-, lapatinib-, pyrotinib-, or afatinib-based combinations. A nonstatistically significant PFS benefit favoring TKI-containing regimens was observed in both patients with BM [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.41-1.12; P = 0.13] and without BM (HR 0.55, 95% CI 0.24-1.26; P = 0.16). Sensitivity analysis, excluding each study singly, demonstrated a significant PFS benefit favoring TKI-containing regimens in patients with BM after the exclusion of afatinib from the analysis (HR 0.56, 95% CI 0.35-0.90; P = 0.016). No statistically significant differences in OS were observed between the comparison groups.
CONCLUSIONS
A trend in PFS favoring TKI-containing regimens was observed in patients with BM. Sensitivity analysis including only trials that evaluated regimens containing tucatinib, lapatinib, or pyrotinib demonstrated a significant PFS benefit favoring TKI-containing regimens in patients with BM.
Topics: Afatinib; Brain Neoplasms; Breast Neoplasms; Female; Humans; Lapatinib; Protein Kinase Inhibitors
PubMed: 35653982
DOI: 10.1016/j.esmoop.2022.100501