Vol 27, No 1 (2024)
- Year: 2024
- Articles: 15
- URL: https://vietnamjournal.ru/1386-2073/issue/view/9927
Chemistry
Generative Grammar vs. Elucidating Epiphany
1-1
Psidium guajava: An Insight into Ethnomedicinal Uses, Phytochemistry, and Pharmacology
Abstract
Background:Psidium guajava (guava) is widely distributed in tropical and subtropical regions and adapted to various environmental conditions. Guava is an important economic fruit widely used as food and folk medicine. It contains flavonoids, alkaloids, tannins, triterpenoids, reducing sugars, essential oils, carotenoids, polyphenols, etc. The presence of triterpenoid acids such as guavacoumaric, ursolic, jacoumaric, guajavanoic, guavenoic, and Asiatic acids helps to develop novel drugs against various diseases. It is used traditionally for medicinal purposes, mainly for antioxidant, antimicrobial, antispasmodic, antidiabetic, anticancer, antiallergy, anti-inflammatory, and hepato-protective properties.
Objective:The systematic literature study aims to summarize its botanical description, phytochemicals, pharmacological activities, and clinical trials. This review focuses on the plants chemical composition and scientific approaches to human welfare.
Methods:A systematic literature search was done on Psidium guajava through previous literature and online databases such as Google Scholar, Pubmed, Science Direct, etc., to explain its ethnomedicinal uses, phytochemistry, and pharmacological applications.
Results:Previous literature studies of Psidium guajava suggest it can serve as antioxidant, antimicrobial, antispasmodic, antidiabetic, anticancer, anti-allergy, anti-inflammatory, and hepatoprotective effects. Successful clinical trials performed on the plant extracts against infantile rotaviral enteritis and infectious gastroenteritis showed future directions to work with the plant for clinical applications.
Conclusion:In this review, an attempt is made to show all literature studied, especially in phytochemistry, pharmacology, clinical trials and uses as traditional folk medicine around the world. The leaves have been used by folklore over the years to treat various ailments such as skin ulcers, diarrhoea, vaginal irritation, cough, conjunctivitis, etc. Further studies are required to explore more therapeutic remedies and to develop new medicines for future perspectives.
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Safety Analysis of Bapineuzumab in the Treatment of Mild to Moderate Alzheimers Disease: A Systematic Review and Meta-Analysis
Abstract
Background:Alzheimers disease affects millions of people worldwide, and very few drugs are available for its treatment. Monoclonal antibodies have shown promising effects in the treatment of various types of diseases. Bapineuzumab is one of the humanized monoclonal antibodies, which have shown promising effects in AD patients. Bapineuzumab has shown efficacy in the treatment of mild to moderate Alzheimers disease. However, its safety is still unclear.
Objective:Thus, the main objective of the current study is to find out the exact safety profile of bapineuzumab in the treatment of mild to moderate Alzheimers disease.
Methods:We performed a web-based literature search of PubMed and clinical trial websites using the relevant keywords. Data were extracted from eligible records, and the risk ratio (RR) was calculated with a 95% confidence interval (CI). All the analyses were performed using Review Manager software (version 5.3 for windows). Heterogeneity was measured by Chi-square and I-square tests.
Results:Non-significant association of bapineuzumab with serious treatment-emergent adverse events [RR: 1.11 (0.92, 1.35)], headache [RR: 1.03 (0.81, 1.32)], delirium [RR: 2.21 (0.36, 13.53)], vomiting [RR: 0.92 (0.55, 1.55)], hypertension [RR: 0.49 (0.12, 2.12)], convulsions [RR:2.23 (0.42, 11.71)], falls [RR: 0.98 (0.80, 1.21)], fatal AEs [RR: 1.18 (0.59, 2.39)], and neoplasms [RR:1.81 (0.07, 49.52)] was reported; however, a significant association was found with vasogenic edema [RR: 22.58 (3.48, 146.44)].
Conclusion:Based on available evidence, bapineuzumab is found to be safe in the treatment of AD patients. However, vasogenic edema should be considered.
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The Value of Epicardial Adipose Tissue for Patients Treated with Percutaneous Coronary Intervention: A Systemic Review and Meta-analysis
Abstract
Background:Recently, some clinical researches have shown epicardial adipose tissue to play a pivotal role in prognosis for patients treated with percutaneous coronary intervention (PCI), but the results are still controversial. A systematic review and meta-analysis was conducted to investigate the value of epicardial adipose tissue for the prognosis of patients treated with PCI.
Method:A systematic search was performed using PubMed, Web of Science, and the Cochrane Library for studies evaluating the association of EAT and patients treated with PCI published up to January 2023. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies. Meta-analysis was performed using Review Manager V.5.3.
Result:Thirteen studies enrolling 3683 patients were eventually included in our study. The thickness or volume of EAT measured were significantly higher in the ISR group compared to those in the non-ISR group (the standard mean difference of 0.34, 95% CI, 0.18-0.49, p(<0.0001; I2=36%). The incidence of no-reflow was significantly higher in the thicker EAT group compared to the thin EAT group (pooled relative ratio 1.52, 95% CI 1.29-1,80, p(<0.0001; I2 =0%). Thicker EAT was significantly associated with MACEs (pooled relative ratio 1.50, 95% 1.18-1.90, p=0.008). A lower EAT volume was associated with larger infarct size in STEMI patients treated with primary PCI (standard mean difference -5.45, 95% CI -8.10, -2.80; p(<0.0001; I2=0%).
Conclusion:In summary, our systemic review and meta-analysis suggests that high EAT is related to a significantly increased risk of non-reflow, MACEs, and decreased infarct size in patients with CAD treated with PCI. This paradox phenomenon demonstrates that the quality of EAT may play a more important role than the sole thickness or volume of EAT.
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Exploring the Mechanism of Si-miao-yong-an Decoction in the Treatment of Coronary Heart Disease based on Network Pharmacology and Experimental Verification
Abstract
Background:To investigate the active ingredients and the mechanisms of Si-miaoyong- an Decoction (SMYA) in the treatment of coronary heart disease (CHD) by using network pharmacology, molecular docking technology, and in vitro validation.
Methods:Through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Uniprot database, GeneCards database, and DAVID database, we explored the core compounds, core targets and signal pathways of the effective compounds of SMYA in the treatment of CHD. Molecular docking technology was applied to evaluate the interactions between active compounds and key targets. The hypoxia-reoxygenation H9C2 cell model was applied to carry out in vitro verification experiments. A total of 109 active ingredients and 242 potential targets were screened from SMYA. A total of 1491 CHD-related targets were retrieved through the Gene- Cards database and 155 overlapping CHD-related SMYA targets were obtained. PPI network topology analysis indicated that the core targets of SMYA in the treatment of CHD include interleukin- 6 (IL-6), tumor suppressor gene (TP53), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), phosphorylated protein kinase (AKT1) and mitogen-activated protein kinase (MAPK). KEGG enrichment analysis demonstrated that SMYA could regulate Pathways in cancer, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxiainducible factor-1(HIF-1) signaling pathway, VEGF signaling pathway, etc.
Results:Molecular docking showed that quercetin had a significant binding activity with VEGFA and AKT1. In vitro studies verified that quercetin, the major effective component of SMYA, has a protective effect on the cell injury model of cardiomyocytes, partially by up-regulating expressions of phosphorylated AKT1 and VEGFA.
Conclusion:SMYA has multiple components and treats CHD by acting on multiple targets. Quercetin is one of its key ingredients and may protect against CHD by regulating AKT/VEGFA pathway.
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Kechuanning Gel Plaster Exerts Anti-inflammatory and Immunomodulatory Effects on Ovalbumin-induced Asthma Model Rats via ERK Pathway
Abstract
Background:We aimed to evaluate the therapeutic effects of Kechuanning gel plaster on ovalbumin (OVA)-induced rat model of asthma.
Methods:Rats were injected with OVA to induce asthma, and Kechuanning gel plaster was administered after the OVA challenge. The immune cell counts in the bronchial alveolar lavage fluid (BALF) were calculated after Kechuanning gel plaster administration. The levels of immune factors in BALF and serum OVA-specific IgE levels were analyzed. Western blot analysis and immunohistochemistry were carried out to analyze the following proteins: C-FOS, C-JUN, RAS p21 protein activator 1 (RASA1), matrix metalloproteinase 9 (MMP9), RAF1, p-MEK1, tissue inhibitor of metalloproteinase-1 (TIMP1), and p-extracellular signal-regulated kinase 1 (ERK1).
Results:Administration of Kechuanning gel plaster led to decreased immune cell counts, inflammatory cytokines (interleukin (IL)-1β, IL13, and IL17), and OVA-specific IgE expression. Compared to the normal group, the C-FOS, C-JUN, RASA1, MMP9, RAF1, MEK1, TIMP1, and p- ERK1 expressions in the model group were significantly increased, whereas Kechuanning gel plaster administration decreased C-JUN, MMP9, TIMP1, RAF1, MEK1, p-ERK1, C-FOS, and RASA1 protein levels.
Conclusion:Kechuanning gel plaster exerted its therapeutic effects on OVA-induced asthma model rats through the ERK signaling pathway. Kechuanning gel plaster could be considered as a potential alternative therapeutic agent for the management of asthma.
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CENPF Upregulation is Associated with Immunosuppressive Status and Poor Clinical Outcomes in Lung Adenocarcinoma Validated by qRT-PCR
Abstract
Objective:CENPF-differentially expressed in various types of cancersis a marker of poor prognosis. However, studies on the impact of CENPF on patient prognosis in lung adenocarcinoma regarding immune infiltration are lacking.
Methods:CENPF expression profiles were analyzed in the GEO and TCGA databases. qRT-PCR was used to verify CENPF mRNA expression in lung adenocarcinoma cell lines. The prognostic value of CENPF was evaluated by combining data from clinical samples in the GEPIA2 and TCGA databases. Metascape and WebGestalt were used for enrichment analysis of gene sets most positively associated with CENPF. Immune cell infiltration score data were retrieved from TCGA and the correlation between CENPF expression and immune cell infiltration was analyzed.
Results:CENPF expression was elevated in 29 types of cancer. CENPF was highly expressed and increased with tumor grade in lung adenocarcinoma. Immunohistochemical and qRT-PCR analyses revealed that CENPF expression was upregulated in lung adenocarcinoma tissues and cells. High expression of CENPF significantly worsened prognoses in patients with multiple malignancies, including lung adenocarcinoma. Results from gene set enrichment analysis indicated significant enrichment of the progesterone-mediated oocyte maturation pathway. Immune infiltration analysis revealed that CD4+ Th2 cell infiltration was significantly higher in the high CENPF expression group.
Conclusion:Upregulation of CENPF expression was related to poor progression-free survival, disease- free survival, and overall survival in patients with lung adenocarcinoma. High expression of CENPF was markedly related to genes associated with the immune checkpoint. Lung adenocarcinoma samples with high CENPF expression had increased CD4+ Th2 cell infiltration. Our findings indicate that CENPF promotes CD4+ Th2 cell infiltration through oncogenic activity and may be used as a biomarker for predicting patient outcomes in lung adenocarcinoma.
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Study on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology Approaches
Abstract
Introduction:Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently.
Methods:Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry.
Results:Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment.
Conclusions:Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.
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Network Toxicology Prediction and Molecular Docking-based Strategy to Explore the Potential Toxicity Mechanism of Metformin Chlorination Byproducts in Drinking Water
Abstract
Background:Metformin (MET), a worldwide used drug for treating type 2 diabetes but not metabolized by humans, has been found with the largest amount in the aquatic environment. Two MET chlorination byproducts, including Y and C, were transformed into drinking water during chlorination. However, the potential toxicity of the byproducts in hepatotoxicity and reproduction toxicity remains unclear.
Methods:The TOPKAT database predicted the toxicological properties of metformin disinfection by-products. The targets of metformin disinfection by-products were mainly obtained from the PharmMapper database, and then the targets of hepatotoxicity and reproductive toxicity were screened from GeneCards. The overlapping targets of toxic component targets and the hepatotoxicity or reproduction toxicity targets were regarded as the key targets. Then, the STRING database analyzed the key target to construct a protein-protein interaction network (PPI) and GO, and KEGG analysis was performed by the DAVID platform. Meanwhile, the PPI network and compound- target network were constructed by Cytoscape 3.9.1. Finally, Discovery Studio 2019 software was used for molecular docking verification of the two toxic compounds and the core genes.
Results:Y and C exhibited hepatotoxicity, carcinogenicity, and mutagenicity evaluated by TOPKAT. There were 22 potential targets relating to compound Y and hepatotoxicity and reproduction toxicity and 14 potential targets relating to compound C and hepatotoxicity and reproduction toxicity. PPI network analysis showed that SRC, MAPK14, F2, PTPN1, IL2, MMP3, HRAS, and RARA might be the key targets; the KEGG analysis indicated that compounds Y and C caused hepatotoxicity through Hepatitis B, Pathways in cancer, Chemical carcinogenesis-reactive oxygen species, Epstein-Barr virus infection; compound Y and C caused reproduction toxicity through GnRH signaling pathway, Endocrine resistance, Prostate cancer, Progesterone-mediated oocyte maturation. Molecular docking results showed that 2 compounds could fit in the binding pocket of the 7 hub genes.
Conclusion:This study preliminarily revealed the potential toxicity and possible toxicity mechanism of metformin disinfection by-products and provided a new idea for follow-up research.
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miR-141-3p Enhanced Radiosensitivity of CRC Cells
Abstract
Background:Colorectal cancer (CRC) is recognized as one of the frequently diagnosed malignancies, and numerous microRNAs (miRs) are identified to be active in CRC.
Objective:This work aimed to clarify the effect of miR-141-3p on the radiosensitivity of CRC cells.
Methods:Firstly, CRC cell lines were cultured and applied to construct radiation-resistant CRC cells via X-ray treatment. The expression levels of miR-141-3p and long non-coding RNA DLX6 antisense RNA 1 (lncRNA DLX6-AS1) in CRC cells were measured using real-time quantitative polymerase chain reaction. After transfection with miR-141-3p mimics and 24 h treatment with 6- MV X-ray (0, 2, 4, 6 Gy), the survival fraction (SF) and the colony formation ability of CRC cells were determined using the cell counting kit-8 and colony formation methods. The interactions between miR-141-3p and DLX6-AS1 were analyzed using the dual-luciferase assay. The impact of miR-141-3p on DLX6-AS1 stability was detected after adding actinomycin-D. The role of DLX6- AS1 in the radiosensitivity of CRC cells was explored by transfecting oe-DLX6-AS1 into radiation- resistant CRC cells overexpressing miR-141-3p.
Results:The relative expression levels of miR-141-3p were downregulated in CRC cells and further declined in radiation-resistant cells. Upregulation of miR-141-3p relative expression reduced SF and the colony formation ability while amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p directly bound to DLX6-AS1 to reduce DLX6-AS1 stability, and therefore downregulated DLX6-AS1 expression. DLX6-AS1 overexpression counteracted the role of miR- 141-3p overexpression in amplifying the radiosensitivity of radiation-resistant CRC cells.
Conclusion:miR-141-3p binding to DLX6-AS1 significantly decreased DLX6-AS1 stability and expression, promoting the radiosensitivity of CRC cells.
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Over-expression of microRNA-145 Elevating Autophagy Activities via Downregulating FRS2 Expression
Abstract
Objectives:Osteoarthritis (OA) is one of the most common chronic and progressive joint diseases characterized by cartilage degeneration and chondrocyte death. In this study, we aimed to identify the modulation effect of miR-145 on chondrocytes' autophagy during the development of OA.
Background:Osteoarthritis (OA) is one of the most prevalent types of chronic and progressive joint disorder with the symptoms of joint pain and stiffness, and it leads to disability at the end stage. In recent years, microRNA-145 (miR-145) has been found to activate autophagy in various cell types, including mesenchymal stem cells, cardiomyocytes, and osteosarcoma cells. However, it is unknown whether miR-145 regulates the progression of OA by influencing chondrocyte autophagy.
Methods:Before investigating the regulatory effect of miR-145 on the autophagic activity of chondrocytes, the expression of miR-145 in human joint samples was analyzed. The targeting relationship between miR-145 and FRS2 was detected by dual luciferase assay. The effect of FRS2 and miR-145 on the autophagic activity of chondrocytes was observed by bidirectional expression of FRS2 and miR-145.
Results:The miR-145 expression and LC3-II/LC3-I ratio were significantly decreased and the SQSTM1 expression was increased in OA patients. The miR-145 overexpression in C20A4 cells increased LC3-II/LC3-I ratio, decreased SQSTM1 expression, and was positively correlated with autophagic activity. Under oxidative stress, miR-145 overexpression significantly improved chondrocyte viability through autophagy stimulation. FRS2 is a potential target of miR-145 via a binding sequence within its 3 UTR. FRS2 acts as the downstream mediator of miR-145 to suppress autophagy through activating PI3K/Akt/mTOR pathways.
Conclusion:The miR-145 acts as a protective factor against chondrocytes by regulating miRFRS2- autophagy axis. The decrease of miR-145 in articular synovial fluid may turn out to be an important marker for early diagnosis of OA, and modulation of miR-145 may represent a promising therapeutic strategy for OA.
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The Potential of Lipid Droplet-associated Genes as Diagnostic and Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma
Abstract
Objective:The role of lipid droplets (LDs) and lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients.
Methods:The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance.
Results:LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P(<0.05). Fifty-three differentially expressed genes, including 34 upregulated and 19 downregulated, were found in HNSCC based on the TCGA platform (P(<0.05). Then, 53 genes were proved to be functionally enriched in lipid metabolism and LDs. Among them, with an AUC value > 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P(<0.05). The significant prognostic factors AUP1, CAV1, CAV2, and SQLE were further identified using the univariate and multivariate cox proportional hazard models (P(<0.05). The protein expression of CAV2 and SQLE was significantly increased in the HNSCC tissue compared to normal tissues (P(<0.05). Finally, the knockdown of the four LD-AGs decreased LDs accumulation, respectively.
Conclusions:Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC.
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Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia
Abstract
Aim:In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models.
Background:VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear.
Objective:The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD.
Methods:The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Students t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05.
Results:AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway.
Conclusion:This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.
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Exploring the Mechanism of Brucea Javanica against Ovarian Cancer based on Network Pharmacology and the Influence of Luteolin on the PI3K/AKT Pathway
Abstract
Background:Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea javanica is effective in treating OC, and the corresponding mechanism is also unknown.
Objective:This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments.
Methods:The essential active components of Brucea javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting.
Results:Luteolin, β-sitosterol and their corresponding targets were selected as the essential active components of Brucea javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway.
Conclusion:It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.
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B2M is a Biomarker Associated With Immune Infiltration In High Altitude Pulmonary Edema
Abstract
Background:High altitude pulmonary edema (HAPE) is a serious mountain sickness with certain mortality. Its early diagnosis is very important. However, the mechanism of its onset and progression is still controversial.
Aim:This study aimed to analyze the HAPE occurrence and development mechanism and search for prospective biomarkers in peripheral blood.
Methods:The difference genes (DEGs) of the Control group and the HAPE group were enriched by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and then GSEA analysis was performed. After identifying the immune-related hub genes, QPCR was used to verify and analyze the hub gene function and diagnostic value with single-gene GSEA and ROC curves, and the drugs that acted on the hub gene was found in the CTD database. Immune infiltration and its association with the hub genes were analyzed using CIBERSORT. Finally, WGCNA was employed to investigate immune invasion cells' significantly related gene modules, following enrichment analysis of their GO and KEGG.
Results:The dataset enrichment analysis, immune invasion analysis and WGCNA analysis showed that the occurrence and early progression of HAPE were unrelated to inflammation. The hub genes associated with immunity obtained with MCODE algorithm of Cytoscape were JAK2 and B2M. RT-qPCR and ROC curves confirmed that the hub gene B2M was a specific biomarker of HAPE and had diagnostic value, and single-gene GSEA analysis confirmed that it participated in MHC I molecule-mediated antigen presentation ability decreased, resulting in reduced immunity.
Conclusion:Occurrence and early progression of high altitude pulmonary edema may not be related to inflammation. B2M may be a new clinical potential biomarker for HAPE for early diagnosis and therapeutic evaluation as well as therapeutic targets, and its decrease may be related to reduced immunity due to reduced ability of MCH I to participate in antigen submission.
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