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Biochemistry. Biokhimiia Jan 2024Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the... (Review)
Review
Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.
Topics: Animals; Humans; Amyotrophic Lateral Sclerosis; RNA-Binding Protein FUS; Motor Neurons; Cytoplasm; Mutation; Disease Models, Animal
PubMed: 38621743
DOI: 10.1134/S0006297924140037 -
Journal of Cancer Research and Clinical... Dec 2023During eukaryotic gene expression, alternative splicing of messenger RNA precursors is critical in increasing protein diversity and regulatory complexity. Multiple... (Review)
Review
During eukaryotic gene expression, alternative splicing of messenger RNA precursors is critical in increasing protein diversity and regulatory complexity. Multiple transcript isoforms could be produced by alternative splicing from a single gene; they could eventually be translated into protein isoforms with deleted, added, or altered domains or produce transcripts containing premature termination codons that could be targeted by nonsense-mediated mRNA decay. Alternative splicing can generate proteins with similar, different, or even opposite functions. Increasingly strong evidence indicates that abnormal RNA splicing is a prevalent and crucial occurrence in cellular differentiation, tissue advancement, and the development and progression of cancer. Aberrant alternative splicing could affect cancer cell activities such as growth, apoptosis, invasiveness, drug resistance, angiogenesis, and metabolism. This systematic review provides a comprehensive overview of the impact of abnormal RNA alternative splicing on the development and progression of hepatocellular carcinoma.
Topics: Humans; Alternative Splicing; RNA; Carcinoma, Hepatocellular; RNA, Messenger; Liver Neoplasms; Protein Isoforms; RNA Splicing
PubMed: 37898981
DOI: 10.1007/s00432-023-05474-8 -
BMC Cancer Feb 2024The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.
BACKGROUND
The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated.
METHODS
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs).
RESULTS
Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34).
CONCLUSIONS
In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.
Topics: Humans; Randomized Controlled Trials as Topic; Stomach Neoplasms; Antibodies, Monoclonal; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Esophagogastric Junction; Claudins; Esophageal Neoplasms
PubMed: 38383390
DOI: 10.1186/s12885-024-11980-w -
p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell Communication and Signaling : CCS Nov 2023Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling.... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling. Although the abnormalities are primarily prompted by chronic exposure to inhaled irritants, maladjusted and self-reinforcing immune responses are significant contributors to the development and progression of the disease. The p38 isoforms are regarded as pivotal hub proteins that regulate immune and inflammatory responses in both healthy and disease states. As a result, their inhibition has been the subject of numerous recent studies exploring their therapeutic potential in COPD.
MAIN BODY
We performed a systematic search based on the PRISMA guidelines to find relevant studies about P38 signaling in COPD patients. We searched the PubMed and Google Scholar databases and used "P38" AND "COPD" Mesh Terms. We applied the following inclusion criteria: (1) human, animal, ex vivo and in vitro studies; (2) original research articles; (3) published in English; and (4) focused on P38 signaling in COPD pathogenesis, progression, or treatment. We screened the titles and abstracts of the retrieved studies and assessed the full texts of the eligible studies for quality and relevance. We extracted the following data from each study: authors, year, country, sample size, study design, cell type, intervention, outcome, and main findings. We classified the studies according to the role of different cells and treatments in P38 signaling in COPD.
CONCLUSION
While targeting p38 MAPK has demonstrated some therapeutic potential in COPD, its efficacy is limited. Nevertheless, combining p38 MAPK inhibitors with other anti-inflammatory steroids appears to be a promising treatment choice. Clinical trials testing various p38 MAPK inhibitors have produced mixed results, with some showing improvement in lung function and reduction in exacerbations in COPD patients. Despite these mixed results, research on p38 MAPK inhibitors is still a major area of study to develop new and more effective therapies for COPD. As our understanding of COPD evolves, we may gain a better understanding of how to utilize p38 MAPK inhibitors to treat this disease. Video Abstract.
Topics: Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 37919729
DOI: 10.1186/s12964-023-01337-4 -
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 -
Pediatric Neurology Apr 2024To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD).
METHODS
A comprehensive literature search was conducted up to October 31, 2022, in PubMed, Embase, Cochrane Library, Web of Science, and Scopus Database. To evaluate the diagnostic value, the sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and Q∗ index were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was used to verify the robustness of the findings.
RESULTS
A total seven studies with 248,853 newborns was included in our meta-analysis. The pooled SEN and SPE were 1.00 (95% confidence interval [CI]: 0.89∼1.00) and 1.00 (95% CI: 1.00 to 1.00), respectively; the PLR and NLR were 1004.59 (95% CI: 251.37∼4014.91) and 0.13 (95% CI: 0.05∼0.34), respectively; the DOR was 877.96 (95% CI: 983.24∼78,366.32); the AUC and Q index were 0.8683 and 0.9326, respectively. Sensitivity analysis showed that two studies had an impact on the pooled results and mainly contributed to the heterogeneity.
CONCLUSIONS
CK-MM test demonstrated high accuracy in newborn screening for DMD and may be a valuable alternative in the early diagnosis of the disease followed by confirmatory genetic testing.
Topics: Humans; Infant, Newborn; Muscular Dystrophy, Duchenne; Neonatal Screening; Isoenzymes; Sensitivity and Specificity; Creatine Kinase
PubMed: 38350306
DOI: 10.1016/j.pediatrneurol.2024.01.010