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Brain Research Jun 2024Apelin has been extensively studied, and emerging experimental evidence suggests that Apelin may have effects on stroke by reducing infarct volume and neurological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Apelin has been extensively studied, and emerging experimental evidence suggests that Apelin may have effects on stroke by reducing infarct volume and neurological deficits, inhibiting the apoptosis process and reducing brain water content. However, the credibility of the evidence is uncertain. Thus, we aimed to perform a systematic review and meta-analysis to evaluate preclinical studies that used Apelin for the treatment of transient focal cerebral ischemia.
METHODS
Electronic bibliographic databases including PubMed, EMBASE, Scopus, and Google Scholar were searched for finding relevant studies from January 2000 to July 2023. The methodological quality and risk of bias scores for animal studies were calculated based on the CAMARADES and the SYRCLE's RoB tools, respectively. The effect sizes were assessed using Comprehensive Meta-Analysis (CMA) software.
RESULTS
A total of twelve eligible studies were used for the systematic review and meta-analysis. The median scores of study quality and risk of bias were 7.5 out of 10, and 5 out of 10, respectively. Apelin treatment effectively decreased infarct volume (primary outcome) [Hedges' g = 2.72, 95 % CI (1.93, 3.51), p < 0.001], neurological deficit [Hedges' g = 1.76, 95 % CI (0.96, 2.55), p < 0.001], cleaved caspase 3 [Hedges' g = 2.16, 95 % CI (0.87, 3.44), p = 0.001], and apoptotic cell number [Hedges' g = 4.07, 95 % CI (1.25,6.89), p = 0.005] compared with the control group. According to subgroup analysis, more notable neuroprotective effects were observed with intravenous administration than with intracerebroventricular (ICV) administration. Moreover, we determined that effect size of infarct volume was markedly related to the species. The combined measurement of two studies demonstrated that Apelin could reduce BCL2 and TNF-α levels as well as brain water content compared with the control group. However, pooled measurement of two studies showed that no relevancy was discovered between CHOP and altering infarct volume.
CONCLUSION
The present meta-analysis was conducted to assess preclinical studies related to Apelin treatment in rodent ischemic stroke. Apelin can exert promising neuroprotective effects by reducing infarct volume, neurological deficit, caspase 3, apoptotic cell number, TNF- α and brain water content and increasing BCL2. The current evidence supports the anti-apoptotic and anti-inflammatory properties of Apelin, but its effectiveness in decreasing CHOP level in animal models of ischemic stroke needs further elucidation. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42023460926.
Topics: Animals; Apelin; Apoptosis; Disease Models, Animal; Ischemic Attack, Transient; Neuroprotective Agents; Reperfusion Injury
PubMed: 38552935
DOI: 10.1016/j.brainres.2024.148887 -
Frontiers in Reproductive Health 2024MicroRNAs are small noncoding genes with gene expression regulatory function. Their emergence as potential diagnostic biomarker for many diseases has gained a specific...
INTRODUCTION
MicroRNAs are small noncoding genes with gene expression regulatory function. Their emergence as potential diagnostic biomarker for many diseases has gained a specific interest among researchers. Observations of changes in miRNA levels correlating with aneuploidy in early embryos raise the prospective of employing miRNA as biomarkers to assess the embryo quality.
METHOD
To identify and gather the miRNAs with potential link to chromosomal abnormalities in embryos from previous research, we conducted a systematic search using four databases, including Embase, Medline, Web of Science, and Cochrane databases in accordance with PRISMA guidelines.
RESULTS
Out of 200 identified records, only seven met the inclusion criteria. Seven miRNAs: miR-19b, miR-517c, miR-518e, miR-522, miR-92a, and miR-106a exhibited persistent downregulation in aneuploid blastocysts in the included studies. These miRNAs are members of important miRNA clusters, associated with abnormal expression in studies on reproductive failure. Pathway analysis revealed their involvement in regulating gene transcription, as well as cell cycle progression and apoptosis.
DISCUSSION
The changes detected in the miRNA expression in aneuploid embryos across different studies support the aneuploidy and miRNA relationship and prospect miRNA as a valuable tool for the assessment of embryo quality. Collectively, these observations highlight the role of miRNAs in embryonic development, and their involvement in genetic abnormalities that occur in embryos, such as aneuploidy, indicating their potential implementation to improve the embryo selection and reproductive outcomes.
PubMed: 38550247
DOI: 10.3389/frph.2024.1370341 -
Frontiers in Pharmacology 2024The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action. The...
The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action. The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5). A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = -1.84, 95% CI -2.14 to -1.55, < 0.00001). It also reduced the percentage of cerebral infarction (SMD = -2.97, 95% CI -3.58 to -2.36, < 0.00001) and brain water content (SMD = -2.37, 95% CI -3.63 to -1.12, = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = -7.53, 95% CI -11.34 to -3.72, = 0.0001), IL-1β (SMD = -2.65, 95% CI -3.87 to -1.44, < 0.0001), and IL-6 (SMD = -5.55, 95% CI -9.32 to -1.78, = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, = 0.0003), NOS (SMD = -1.52, 95% CI -2.98 to -0.06, = 0.04), MDA (SMD = -5.31, 95% CI -8.48 to -2.14, = 0.001), and NO (SMD = -5.33, 95% CI -8.82 to -1.84, = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = -5.21, 95% CI -7.47 to -2.94, < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, < 0.0001). Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.
PubMed: 38545549
DOI: 10.3389/fphar.2024.1373663 -
International Journal of Molecular... Mar 2024Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22...
Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.
Topics: Humans; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Signal Transduction
PubMed: 38542279
DOI: 10.3390/ijms25063307 -
International Journal of Molecular... Mar 2024Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast...
Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.
Topics: Animals; Female; Humans; Apoptosis; Cell Line, Tumor; Cell Proliferation; Reproducibility of Results; Triple Negative Breast Neoplasms
PubMed: 38542225
DOI: 10.3390/ijms25063254 -
Journal of Personalized Medicine Feb 2024Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit... (Review)
Review
BACKGROUND
Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance.
METHODS
A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects.
RESULTS
Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%).
CONCLUSIONS
The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.
PubMed: 38541003
DOI: 10.3390/jpm14030261 -
Antioxidants (Basel, Switzerland) Mar 2024Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities.... (Review)
Review
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities. Although pharmacological interventions have revealed promising prospects in the management of SCA3, adverse effects may become unbearable. The use of herbal remedies in traditional Chinese medicine (TCM) may serve as potential alternative medicines to delay the progression of the disease. This systematic review is intended to identify, appraise, and summarize the findings of studies pertaining to the therapeutic roles of herbal remedies in TCM targeting oxidative stress in the management of SCA3. A literature search for relevant articles published from 1 January 2013 to 30 June 2023 in three databases, namely PubMed, Web of Science, and Scopus, was carried out according to the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of ten preclinical studies met the inclusion criteria of the systematic review. We recognized the therapeutic potential of , , sp., , , , , , sp., , , , , and . We identified the types of preclinical models expressing polyglutamine (polyQ) expanded mutant protein (mATXN3), inducers of oxidative stress that mimic the SCA3 pathogenesis, and effective doses of the herbal remedies. The modes of action contributing to the attenuation of oxidative stress are activation of antioxidant pathways, ubiquitin-proteasome system and autophagy, regulation of apoptosis, proinflammatory signaling pathway and chaperones, regulation of mitochondrial function and biogenesis, and restoration of neurotransmission and synaptic plasticity. In conclusion, herbal remedies in TCM may possibly delay the progression of SCA3, therefore providing justification for clinical trials.
PubMed: 38539908
DOI: 10.3390/antiox13030375 -
Antioxidants (Basel, Switzerland) Mar 2024Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis,... (Review)
Review
Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis, necroptosis, and autophagy. It is characterized by the accumulation of intracellular iron, overproduction of reactive oxygen species, depletion of glutathione, and extensive lipid peroxidation of lipids in the cell membrane. It was discovered that ferroptosis is interconnected with many diseases, such as neurodegenerative diseases, ischemia/reperfusion injury, cancer, and chronic kidney disease. Polyphenols, plant secondary metabolites known for many bioactivities, are being extensively researched in the context of their influence on ferroptosis which resulted in a great number of publications showing the need for a systematic review. In this review, an extensive literature search was performed. Databases (Scopus, Web of Science, PubMed, ScienceDirect, Springer) were searched in the time span from 2017 to November 2023, using the keyword "ferroptosis" alone and in combination with "flavonoid", "phenolic acid", "stilbene", "coumarin", "anthraquinone", and "chalcone"; after the selection of studies, we had 311 papers and 143 phenolic compounds. In total, 53 compounds showed the ability to induce ferroptosis, and 110 compounds were able to inhibit ferroptosis, and out of those compounds, 20 showed both abilities depending on the model system. The most researched compounds are shikonin, curcumin, quercetin, resveratrol, and baicalin. The most common modes of action are in the modulation of the Nrf2/GPX4 and Nrf2/HO-1 axis and the modulation of iron metabolism.
PubMed: 38539867
DOI: 10.3390/antiox13030334 -
Marine Drugs Feb 2024Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the... (Review)
Review
Non-small-cell lung cancer (NSCLC), the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, has been extensively investigated in the last decade in terms of developing new therapeutic options that increase patient survival. In this context, marine animals are a source of new, interesting bioactive molecules that have been applied to the treatment of different types of cancer. Many efforts have been made to search for new therapeutic strategies to improve the prognosis of lung cancer patients, including new bioactive compounds and cytotoxic drugs from marine sponges. Their antitumoral effect can be explained by several cellular and molecular mechanisms, such as modulation of the cell cycle or induction of apoptosis. Thus, this systematic review aims to summarize the bioactive compounds derived from marine sponges and the mechanisms by which they show antitumor effects against lung cancer, exploring their limitations and the challenges associated with their discovery. The search process was performed in three databases (PubMed, SCOPUS, and Web of Science), yielding a total of 105 articles identified in the last 10 years, and after a screening process, 33 articles were included in this systematic review. The results showed that these natural sponge-derived compounds are a valuable source of inspiration for the development of new drugs. However, more research in this field is needed for the translation of these novel compounds to the clinic.
Topics: Animals; Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Biological Products; Apoptosis; Porifera
PubMed: 38535442
DOI: 10.3390/md22030101 -
Frontiers in Oncology 2024Osteosarcoma (OS) is the most common bone malignant tumor in children and adolescents. Recent research indicates that non-coding RNAs (ncRNAs) have been associated with...
BACKGROUND
Osteosarcoma (OS) is the most common bone malignant tumor in children and adolescents. Recent research indicates that non-coding RNAs (ncRNAs) have been associated with OS occurrence and development, with significant progress made in this field. However, there is no intelligent structure prediction and literature visualization analysis in this research field. From the perspective of intelligent knowledge structure construction and bibliometrics, this study will comprehensively review the role of countries, institutions, journals, authors, literature citation relationships and subject keywords in the field of ncRNAs in OS. Based on this analysis, we will systematically analyze the characteristics of the knowledge structure of ncRNAs in OS disease research and identify the current research hotspots and trends.
METHODS
The Web of Science Core Collection (WoSCC) database was searched for articles on ncRNAs in OS between 2001 and 2023. This bibliometric analysis was performed using VOSviewers, CiteSpace, and Pajek.
RESULTS
This study involved 15,631 authors from 2,631 institutions across 57 countries/regions, with a total of 3,642 papers published in 553 academic journals. China has the highest number of published papers in this research field. The main research institutions include (n = 129, 3.54%), (n = 128, 3.51%), (n = 110, 3.02%), and (n = 109, 2.99%). (n =139, 3.82%), (120, 3.31%), and (n = 95, 2.61%) are the most popular journals in this field, with being the most co-cited journal (Co-Citation = 4,268). , and published the most papers, with being the most co-cited author. and are the main focuses of ncRNAs in OS studies. Key themes include and . Since 2020, hotspots and trends in ncRNA research in OS include and
CONCLUSION
This study represents the first comprehensive bibliometric analysis of the knowledge structure and development of ncRNAs in OS. These findings highlight current research hotspots and frontier directions, offering valuable insights for future studies on the role of ncRNAs in OS.
PubMed: 38532928
DOI: 10.3389/fonc.2024.1255061