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CNS Neuroscience & Therapeutics Apr 2024Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.
AIMS
Several studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.
METHODS
A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.
RESULTS
Overexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).
DISCUSSION
The correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).
CONCLUSION
The overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.
Topics: Humans; Alzheimer Disease; CCAAT-Enhancer-Binding Protein-beta; Disease Progression; Animals; Amyloid beta-Peptides
PubMed: 38644578
DOI: 10.1111/cns.14721 -
Cancer Medicine Apr 2024Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC.
METHODS
We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs.
RESULTS
This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS).
CONCLUSIONS
In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.
Topics: Humans; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Recurrence, Local; Prognosis; RNA, Long Noncoding; RNA, Small Nucleolar
PubMed: 38634194
DOI: 10.1002/cam4.7200 -
Asian Pacific Journal of Cancer... Mar 2024This review investigated the association of COX-2, TNF-α, TLR4, and IKKα with the survival of patients with oral squamous cell carcinoma (SCC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review investigated the association of COX-2, TNF-α, TLR4, and IKKα with the survival of patients with oral squamous cell carcinoma (SCC).
METHODS
A systematic search was conducted in the databases PUBMED, Web of Science, LILACS, EMBASE, Scopus, and Cochrane Library. The studies should assess the expression of those proteins in the tumor and survival outcomes.
RESULTS
Twenty-one articles were included. The meta-analysis results leaned towards an association of COX-2 overexpression with a lower overall survival. The estimated hazard ratio was 1.51 (95% CI 0.97, 2.33), but not statistically significant (p=0.07). A low heterogeneity was observed (I2=0%). Regarding TNF-α, TLR4, and IKKα, statistically significant results for the association with survival were presented, but there was not enough data to a meta-analysis.
CONCLUSION
COX-2 overexpression may be associated with a poorer prognosis in oral SCC. The insufficiency of studies about TNF-α, TLR4, and IKKα restrained their validation as predictors of prognosis.
Topics: Humans; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Tumor Necrosis Factor-alpha; I-kappa B Kinase; Cyclooxygenase 2; Toll-Like Receptor 4; Mouth Neoplasms; Prognosis; Head and Neck Neoplasms
PubMed: 38546058
DOI: 10.31557/APJCP.2024.25.3.757 -
International Journal of Molecular... Mar 2024Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review,... (Review)
Review
Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review, following PRISMA-ScR guidelines, systematically identified and evaluated clinical studies on the impact of CD44 expression on chemotherapy treatment outcomes across various cancer types. The search encompassed PubMed (1985-2023) and SCOPUS (1936-2023) databases, yielding a total of 12,659 articles, of which 40 met the inclusion criteria and were included in the qualitative synthesis using a predefined data extraction table. Data collected included the cancer type, sample size, interventions, control, treatment outcome, study type, expression of CD44 variants and isoforms, and effect of CD44 on chemotherapy outcome. Most of the studies demonstrated an association between increased CD44 expression and negative chemotherapeutic outcomes such as shorter overall survival, increased tumor recurrence, and resistance to chemotherapy, indicating a potential role of CD44 upregulation in chemoresistance in cancer patients. However, a subset of studies also reported non-significant relationships or conflicting results. In summary, this scoping review highlighted the breadth of the available literature investigating the clinical association between CD44 and chemotherapeutic outcomes. Further research is required to elucidate this relationship to aid clinicians in managing CD44-positive cancer patients.
Topics: Humans; Drug Resistance, Neoplasm; Hyaluronan Receptors; Treatment Outcome
PubMed: 38542115
DOI: 10.3390/ijms25063141 -
Reproductive Biology Jun 2024Conflicting findings have emerged regarding the levels of high mobility group box 1 (HMGB1) in individuals experiencing adverse pregnancy outcomes. Here we conducted a... (Meta-Analysis)
Meta-Analysis Review
Conflicting findings have emerged regarding the levels of high mobility group box 1 (HMGB1) in individuals experiencing adverse pregnancy outcomes. Here we conducted a meta-analysis to assess the association between maternal blood HMGB1 levels and adverse pregnancy outcomes. Utilizing databases such as PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Embase and China National Knowledge Infrastructure (CNKI), a systematic literature search was conducted in January 2024. Eligible literature was screened according to inclusion and exclusion criteria. Quality assessment was evaluated using the Newcastle-Ottawa Scale (NOS). The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. 21 observational studies with a total of 2471 participants were included in this meta-analysis. Significantly higher peripheral blood levels of HMGB1 were associated with preeclampsia (PE) (SMD=1.34; 95% CI: 0.72-1.95; P < 0.0001) and gestational diabetes mellitus (GDM) (SMD=1.20; 95% CI: 0.31-2.09; P = 0.009). Additionally, HMGB1 levels in peripheral blood were significantly elevated in patients with unexplained recurrent spontaneous abortion (URSA) than those in pregnancy controls (SMD=4.22; 95% CI: 1.64-6.80; P = 0.001) or non-pregnancy controls (SMD=3.87; 95% CI: 1.81-5.92; P = 0.0002). Interestingly, higher blood HMGB1 levels were observed in women with preterm birth (PTB), however, the results did not reach a statistical difference (SMD=0.54; 95% CI: -0.36-1.44; P = 0.24). In conclusion, overexpressed maternal blood HMGB1 levels were associated with adverse pregnancy outcomes, including PE, GDM and URSA. Further studies should be conducted to validate the efficacy of HMGB1 as a biomarker for assessing the risk of adverse pregnancy outcomes.
Topics: Pregnancy; Female; Humans; HMGB1 Protein; Pregnancy Outcome; Diabetes, Gestational; Pre-Eclampsia; Biomarkers; Pregnancy Complications; Premature Birth
PubMed: 38492434
DOI: 10.1016/j.repbio.2024.100859 -
Iranian Journal of Medical Sciences Feb 2024Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic... (Review)
Review
BACKGROUND
Some studies have evaluated the manipulation of the sonic hedgehog (Shh) signaling pathway to generate more efficient insulin-producing cells (IPCs). In a systematic review, we evaluated and studies on the effect of inhibition or activation of the Shh pathway on the production, differentiation, maintenance, and endocrine activity of IPCs.
METHODS
A systematic review was conducted using all available experimental studies published between January 2000 and November 2022. The review aimed at determining the effect of Shh manipulation on the differentiation of stem cells (SCs) into IPCs. Keywords and phrases using medical subject headings were extracted, and a complete search was performed in Web of Science, Embase, ProQuest, PubMed, Scopus, and Cochrane Library databases. The inclusion criteria were manipulation of Shh in SCs, SCs differentiation into IPCs, and endocrine activity of mature IPCs. Articles with incomplete data and duplications were excluded.
RESULTS
A total of 208 articles were initially identified, out of which 11 articles were included in the study. The effect of Shh inhibition in the definitive endoderm stage to produce functional IPCs were confirmed. Some studies showed the importance of Shh re-activation at late-stage differentiation for the generation of efficient IPCs. It is proposed that baseline concentrations of Shh in mature pancreatic β-cells affect insulin secretion and endocrine activities of the cells. However, Shh overexpression in pancreatic β-cells ultimately leads to improper endocrine function and inadequate glucose-sensing insulin secretion.
CONCLUSION
Accurate manipulation of the Shh signaling pathway can be an effective approach in the production and maintenance of functional IPCs.
Topics: Hedgehog Proteins; Insulin; Cell Differentiation; Signal Transduction; Insulin-Secreting Cells
PubMed: 38356490
DOI: 10.30476/ijms.2023.95425.2678 -
Cell Journal Jan 2024Leucine-rich G protein-coupled receptor 5 () is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on...
Clinical Implications and Prognostic Value of Leucine-Rich G Protein-Coupled Receptor 5 Expression as A Cancer Stem Cell Marker in Malignancies: A Systematic Review and Meta-Analysis.
Leucine-rich G protein-coupled receptor 5 () is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on correlation between LGR5 expression and poor prognosis/ clinicopathological parameters in cancer patients. Therefore, our purpose in conducting this study was to investigate correlation between expression and outcomes of cancer patients under study through a systematic review and meta-analysis. Relevant articles were searched and collected using EMBASE, PubMed, Science Direct, and Scopus databases until December 21, 2022. This study was conducted to examine correlation between expression and different clinical outcomes, such as recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of the included cancer patients. To achieve this, hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were used as statistical measures. A meta-analysis was conducted using STATA 12.0 software. Finally, 53 studies including 9523 patients met the inclusion criteria. Significantly, high-level expression of was related to poor prognosis in terms of OS, higher tumor stage, presence of distant metastasis, and presence of lymph node metastasis. It was discovered through subgroup analysis that several factors, including the study area, evaluation method, and type of cancer, can influence the correlation between expression and negative prognosis in cancer patients. According to the results of our study, overexpression was related to poor OS in cancer patients. In addition, clinicopathological data indicated an unfavorable prognosis in cancer patients with high expression. In conclusion, may serve as a potential prognostic marker for predicting survival in certain cancer types.
PubMed: 38351725
DOI: 10.22074/cellj.2023.2010157.1396 -
Seminars in Nuclear Medicine Mar 2024The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a... (Review)
Review
The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a theranostic framework. Various radioligands targeting GRPR have undergone investigation in preclinical and clinical studies related to breast cancer. This systematic scoping review aimed to assess the current evidence on GRPR-targeted radioligands for diagnostic and therapeutic applications in breast cancer. The methodology followed the PRISMA-ScR protocol. The literature search was conducted in September 2023 and encompassed MEDLINE, Embase, Cochrane, and Scopus databases. We included original peer-reviewed studies focused on breast cancer patients or in vivo breast cancer models. Two reviewers performed the study selection process independently. Data were extracted, synthesized, and categorized into preclinical and clinical studies, further subdivided based on radioligand properties. A total of 35 original studies were included in the review, with three of them evaluating therapeutic outcomes. The results indicated that GRPR-radioantagonists are superior to GRPR-agonists, exhibiting preferable in vivo stability, rapid, specific tumor targeting, and enhanced retention. Both preclinical and clinical evaluations demonstrated renal excretion and high uptake in normal GRPR-expressing tissue, primarily the pancreas. A significant positive correlation was observed between GRPR and estrogen-receptor expression. In the clinical setting, GRPR-radioligands effectively detected primary tumors and, to a lesser extent, lymph node metastases. Moreover, GRPR-targeted radioantagonists successfully identified distant metastases originating from various sites in advanced metastatic disease, strongly correlated with positive estrogen receptor expression. Preclinical therapeutic evaluation of GRPR-radioligands labeled with lutetium-177 showed promising tumor responses, and none of the studies reported any observed or measured side effects, indicating a safe profile. In conclusion, the evidence presented in this review indicates a preference for GRPR-targeted antagonists over agonists, owing to their superior kinetics and promising diagnostic potential. Clinical assessments suggested diagnostic value for GRPR-targeted theranostics in breast cancer patients, particularly those with high estrogen receptor expression. Nevertheless, in the therapeutic clinical context, paying attention to the radiation dose administered to the pancreas and kidneys is crucial.
Topics: Humans; Female; Receptors, Bombesin; Breast Neoplasms; Precision Medicine; Receptors, Estrogen
PubMed: 38342656
DOI: 10.1053/j.semnuclmed.2024.01.004 -
Biology of Sex Differences Jan 2024The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.
METHODS
A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.
RESULTS
Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.
CONCLUSIONS
Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.
Topics: Humans; Male; Female; Alzheimer Disease; MicroRNAs; Brain
PubMed: 38297404
DOI: 10.1186/s13293-024-00588-1 -
Current Cancer Drug Targets Jan 2024Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast...
BACKGROUND
Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast cancer cells. However, there is a need to summarize the evidence to provide conclusive advice on the benefit of PI3K inhibitors in breast cancer patients. Therefore, this review assessed the effectiveness and safety of the PI3K inhibitors amongst breast cancer patients.
METHODS
Searches were made in PubMed Central, EMBASE, MEDLINE, SCOPUS, CENTRAL, WHO trial registry and Clinicaltrials.gov up to December 2022. Meta-analysis was executed using the random-effects model. Pooled hazard ratio (HR)/risk ratio (RR) was reported with 95% confidence intervals (CIs).
RESULTS
In total, 13 studies were included in the analysis. Most were multi-country studies and had a higher risk of bias. Regarding the efficacy parameters, pooled HR for progression-free survival was 0.79 (95%CI: 0.67-0.92), pooled RR for complete response was 1.54 [95%CI: 1.14 to 2.09], partial response was 1.18 [95%CI: 0.87-1.61], overall response was 1.20 [95%CI: 0.93-1.56], stable disease was 1.09 [95%CI: 0.78-1.53], progressive disease was 0.80 [95%CI: 0.74 to 0.87], and clinical benefit was 1.08 [95%CI: 0.80-1.49]. For safety parameters, pooled RR for hyperglycemia was 4.57 [95%CI: 3.15-6.62], and gastrointestinal toxicity was 1.82 [95%CI: 1.56 to 2.14].
CONCLUSION
PI3K inhibitors had better efficacy than the present standard of concern for patients with breast cancer, especially among patients with PIK3CA mutations. Hence, clinicians and oncologists can provide this drug for the target population with extra caution for diabetes patients.
PubMed: 38275057
DOI: 10.2174/0115680096266181231207110048