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Stability analysis of the SEIRS epidemic model with infectious dynamics during latent and infectious periods
Get PDFCoronary pneumonia caused by the SARS-CoV-2 virus was one of the most significant public health threats in recent years. In this paper, we develop and investigate an SEIRS epidemic model that incorporates infectivity during both the latent and infectious stages to characterize the transmission dynamics of COVID-19. By calculating the basic reproduction number (R0) and applying monotonic dynamical system theory along with geometric methods, we validate the threshold theorem. Our analysis demonstrates that the disease-free equilibrium is globally stable when R0 < 1, while the endemic equilibrium becomes globally stable when R0 > 1
Event-triggered reinforcement learning-based internet data bandwidth allocation technique as a metric for balanced QoS and QoE
Get PDFThis research work studies the performance and management of the internet services of institutions of higher learning in Nigeria. Data were collated from a federal, state, and private university designated as FEDERAL1, STATE1, and PRIVATE1, respectively, in this research study. The reinforcement learning-based internet data bandwidth allocation model was developed for bandwidth allocation and prediction to enhance balanced quality of service (QoS) and quality of experience (QoE) of the users. The linear Lagrange’s method of interpolation, the LILARINT model, was developed and implemented to predict and allocate effective internet data bandwidth for the significantly increasing number of internet users in each of the institutions. The problem of inability to predict and allocate acceptable internet data bandwidth with the corresponding number of internet users was solved by the LILARINT model. The Allen’s PRESS regression, R2 of the LILARINT models, was very close to unity, which is an indication that the models developed stood at the very best fit. In this research work, it is clear that PRESS regressions, R2 for the selected institutions, were better than the regression, R2 obtained from Nielsen’s institution. Using the measured and simulated results, we found out that PRESS regression, R2 has significantly performed best in the LILARINT model developed. In the overall comparative analysis, the FEDERAL1 LILARINT model emerged as the most reliable model developed and implemented. The model has a regression, R2 of 0.9999, mean squared error (MSE) of 1.455, mean absolute deviation (MAD) of 122.6920, Standard Deviation (σ) of 8.2975, and mean absolute percentage error (MAPE) of 0.6274%
The Clinical Significance of Procalcitonin Level Changes in Persistent Atrial Fibrillation with Heart Failure
No full textBackground: This study aimed to explore the relevant factors and clinical significance of procalcitonin (PCT) levels in patients diagnosed with persistent atrial fibrillation (AF) and heart failure (HF). However, AF is the most common cardiac arrhythmia, while HF is a clinical syndrome characterized by the hearts inability to pump sufficient blood to meet the bodys metabolic demands. While PCT has been widely used for the clinical diagnosis of infectious diseases, its role in non-infectious diseases, particularly cardiovascular diseases, remains unclear. Methods: We conducted a cross-sectional observational study involving 286 hospitalized patients diagnosed with persistent AF and HF. Peripheral venous blood samples were collected, and PCT levels were assessed using the chemiluminescence immunoassay method. Moreover, clinical data, including HF severity, ventricular rate, age, and other variables of the study cohort were recorded. Furthermore, nonparametric tests were used to compare PCT levels among different groups, and multiple logistic regression analysis was employed to explore potential factors influencing PCT levels. Results: We observed that PCT levels were significantly associated with HF severity, ventricular rate, and age, even after adjusting for other clinical variables. The odds of having a positive PCT level (defined as >0.05 ng/mL) increased by 2.74 times for each increase in HF grade, by 3.21 times for a ventricular rate of ≥110 bpm compared to <110 bpm, and by 1.05 times for each year of age. These findings suggest that PCT could serve as a potential biomarker for the diagnosis and assessment of HF in patients with AF, as well as an indicator of the cardiovascular stress or damage associated with AF. Conclusion: This study provides new insights into the potential of PCT in AF and HF, highlighting the need for additional investigations on the causal relationship and underlying biological pathways between PCT and these factors, as well as the diagnostic and prognostic significance of PCT in this population
Establishment of PBMC-Derived Humanized Breast Cancer Mouse Model for Exploring the Effectiveness of PD-1 Targeted Immunotherapy
No full textBackground: Among the limited therapeutic strategies for late-stage or triple-negative breast cancer (TNBC), immunotherapy has become an available method to prolong lifespan. Therefore, we aimed to explore immunotherapy response markers in humanized mice models to identify sub-populations that respond positively to immunotherapy. Method: A mixture of peripheral blood mononuclear cells (PBMCs) and human breast cancer cells MDA-MB-231 was injected into mice to develop a PBMC cell line-derived xenograft (CDX) mouse model. The mice were treated with pembrolizumab, a programmed cell death protein-1 (PD-1) specific antibody. The tumor growth was monitored and recorded, and tumor volume was calculated using caliper measurements. The immunophenotyping was carried out using flow cytometry. The screening of differentially expressed genes and functional enrichment analysis were done through RNAseq and bioinformatics. Results: A gradual decrease in tumor size was observed on day 7, day 10, and day 14 within the PD-1 treated group compared to the control group, although no statistical significance was observed (p > 0.05). Compared to the control group, RNAseq analysis on day 14 of the PD-1 treated group revealed nine genes with significant changes, including one upregulated gene and eight downregulated genes. Using the GSE124821 dataset, it was found that Nucleoporin 210 kDa (NUP210) was downregulated in both studies (p < 0.05) and proved to be responsive to immunotherapy in the validation dataset (GSE169246). Additionally, pathway analysis revealed that NUP210 is crucial in an immune response process. Conclusions: Our study demonstrated that pembrolizumab could control tumors driven by the MDA-MB-231 cell line. Additionally, we identified NUP210 as a potential responsive marker for immunotherapy of pembrolizumab in breast cancer. These findings may provide significant insights into the future of breast cancer treatment
Osteopontin as a Biomarker for Early Diagnosis of Renal Damage during Experimental Metabolic Syndrome
No full textBackground: Excess consumption of fructose is a significant factor in the development of metabolic syndrome (MetS). It may also play a role in the progress of chronic kidney disease (CKD). Osteopontin (OPN) is a pleiotropic, multi-phosphorylated glycoprotein which plays important roles in diseases as well as in a wide range of biological activities. Based on these findings, the aim of this study was to evaluate OPN as a biomarker for the early detection of renal injury during an experimental model of fructose associated MetS in mice. Methods: Male CD1 mice aged 8–10 weeks were used. Fructose mice were given 30% fructose solution in drinking water, while control mice were given normal drinking water for 56 days. At sacrifice, kidneys, blood and urine of mice were collected. Biochemical, histological (hematoxylin and eosin and Massons trichrome), immunohistochemical and molecular analyses (western blot, real-time quantitative polymerase chain reaction (RT-qPCR)) were performed. Results: Compared to controls, Fructose mice showed increased levels of glucose, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), as well as creatinine and blood urea nitrogen (BUN). In addition, significant histological kidney injury and fibrosis were observed in Fructose mice. These alterations were associated with increased levels of plasma and renal tissue OPN. Conclusions: Thus, new biomarkers such as OPN can be clinically useful to help predict kidney damage in MetS
Berberine Combined with Cisplatin Promotes Apoptosis of NSCLC Cells
No full textBackground: Growing evidence supports the pivotal role of berberine in non-small-cell lung cancer (NSCLC) and its ability to confer cisplatin resistance in NSCLC. This study aimed to investigate the impact of berberine on NSCLC cells. Methods: A549 and H1299 cells were selected as the subjects of this study, and cisplatin-resistant cell lines were established. Cell counting kit 8 (CCK-8) was utilized to assess cell vitality, while cell apoptosis was quantified through the TUNEL (TdT-mediated dUTP nick-end labeling) test. The influence of berberine on cell proliferation was examined using a colony formation test and EdU (5-ethynyl-2′-deoxyuridine). Western blotting was employed to identify the effects of cisplatin and berberine on the expression levels of the phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway. Results: The results indicate that 40 μm berberine significantly decreased the activity of NSCLC cells, without significantly affecting the activity of normal cells (Human Normal Lung Epithelial Cells, BEAS-2B). Berberine reduced the growth of A549 and H1299 cells and accelerated cell apoptosis. Furthermore, experimental data revealed that berberine could attenuate the resistance of NSCLC cells to cisplatin. Cisplatin-resistant cell lines of A549 and H1299 were established, showing that 15 μm cisplatin had no noticeable impact on the proliferation and apoptosis rates of drug-resistant cell lines. However, co-treatment with berberine and 15 μm cisplatin significantly reduced the proliferation of the drug-resistant cell lines and increased apoptosis rates. Western blot results indicated that drug-resistant cells treated with cisplatin had lower phosphorylation levels of PI3K and AKT than the control group. However, a substantial decrease in PI3K and AKT phosphorylation levels was observed when drug-resistant cells were co-treated with berberine. Conclusion: Berberine effectively suppressed the proliferation of NSCLC cells and, when combined with cisplatin, induced apoptosis in these cells
Erastin Enhances Bortezomib Efficacy Through ROS-Mediated DNA Damage Repair and Ferroptosis in Multiple Myeloma
No full textBackground: Multiple myeloma (MM) is characterized by destructive osteolytic lesions, hypercalcemia, renal insufficiency, and anemia. However, bortezomib (Btz) has been recognized as a cornerstone treatment for various types of MM. Therefore, this study explored the effect of erastin on the efficacy of Btz and evaluated the synergistic effects of erastin in combination with Btz on MM cells. Methods: Glutathione (GSH) level was evaluated in MM cell lines to determine its effects on redox balance and cell growth. Furthermore, Solute Carrier Family 7 Member 11 (SLC7A11) was inhibited in MM cells using small-interfering RNA (siRNA) and erastin to determine its effect of redox balance on cell proliferation. Moreover, western blot analysis, flow cytometry, and ferroptosis-related verification experiments were employed to assess the changes that occur after treatment in the cell cycle, the expression of DNA damage repair marker protein, and ferroptosis. Additionally, the synergistic zero interaction potency (ZIP) scores and combination indexes (CIs) of these two drugs were calculated using different concentrations of Btz and erastin, and MM cell proliferation was compared when treated with single and combined drugs. Results: It was observed that increased GSH levels (p < 0.05) disrupted the redox equilibrium and promoted MM cell proliferation. Moreover, activation of siSLC7A11 induced the Ataxia Telangiectasia and Rad3-related Checkpoint Kinase 1 (ATR-CHK1) DNA repair pathway, resulting in a decrease in GSH levels (p < 0.05), a rise in intracellular reactive oxygen species (ROS) levels, alterations in intracellular redox equilibrium, and the induction of ferroptosis. Additionally, the ATR-CHK1 DNA repair pathway resulted in cell cycle S-phase arrest and effectively reduced MM cell growth. However, inhibiting SLC7A11 (p < 0.05) led to higher MM cell response to Btz. Moreover, the combination of erastin and Btz significantly increased cytotoxicity in MM cells (p < 0.05). Conclusion: Erastin increases the level of reactive oxygen species (ROS) in MM cells by inhibiting SLC7A11, which activates the ATR-CHK1 DNA damage repair pathway and causes MM cells to ferroptosis. Furthermore, erastin synergistically increases the cytotoxicity of Btz in multiple myeloma
Upregulated AGMAT is Associated with Prognosis in Colorectal Cancer
No full textBackground: Agmatinase (AGMAT) has been specifically reported to be highly expressed in several malignancies. Therefore, this study aims to investigate the role of AGMAT in colorectal cancer (CRC) and assess its potential as a prognostic biomarker. Methods: We used The Cancer Genome Atlas (TCGA) database to identify differentially expressed genes in CRC compared to the healthy controls. Subsequently, we performed enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases to gain insights into the biological processes and cellular signaling pathways influenced by these differentially expressed genes (DEGs). The most informative prognostic genes among these DEGs were predicted by combining Least Absolute Shrinkage and Selection Operator (LASSO) regression and best subset selection, ultimately identifying the eight most relevant genes. Furthermore, we developed gene-based risk scores using Cox coefficients for these eight prognostic genes. The prognostic ability of the risk score was evaluated using two methods: time-dependent receiver operating characteristic (ROC) analysis and Kaplan-Meier (KM) survival analysis. Additionally, the correlation between AGMAT expression and prognosis in CRC tissues was investigated utilizing GEPIA 2 and the Human Protein Atlas (HPA) database. Finally, we employed RT-qPCR to quantify AGMAT mRNA expression levels in CRC tissues samples. Results: Our analysis of TCGA data revealed 1917 DEGs, including 928 upregulated and 989 downregulated genes. Among them, 8 genes, including Matrix Metallopeptidase 1 (MMP1), Serine Protease Inhibitor Kazal-Type 1 (SPINK1), Cluster of Differentiation 24 (CD24), Serine Protease Inhibitor Kazal-Type 4 (SPINK4), AGMAT, EPH Receptor B2 (EPHB2), C2 Calcium-Dependent Domain Containing 4A (C2CD4A), Pituitary Tumor-Transforming Gene 1 (PTTG1), were significantly associated with prognosis in CRC. Furthermore, we observed upregulated AGMAT expression in CRC tissues. Additionally, we found a significant association between elevated AGMAT expression and decreased overall survival (OS) and disease-free survival (DFS) in patients with CRC (p-value < 0.05). Conclusions: This study demonstrates that AGMAT is highly expressed in CRC tissues and is significantly associated with poorer prognosis in CRC patients. These findings suggest that AGMAT expression could serve as a biomarker for predicting survival in CRC, potentially offering new insights into its role in CRC development and paving the way for future treatment options
FIZZ1 Promotes Atherosclerosis by Enhancing Proliferation, Migration, and Angiogenesis of Aortic Endothelial Cells
No full textBackground: Atherosclerosis is one of the primary causes of cardiovascular diseases. Previous studies have demonstrated the significant role of the Found in Inflammatory Zone 1 (FIZZ1) in the development of atherosclerosis. Therefore, this study aims to explore the potential mechanisms of FIZZ1 in atherosclerosis. Methods: The mouse aortic endothelial cells were utilized in the present study. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) and RNA sequencing approaches were employed to assess the impact of FIZZ1 on vascular generation-related genes as well as the expression of differentially expressed genes (DEGs) in endothelial cells. Furthermore, gene functional annotation and pathway enrichment analyses were conducted using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for FIZZ1-induced differentially expressed genes (DEGs). Additionally, Cell Counting Kit-8 and 5-ethynyl-20-deoxyuridine (EdU) assays were utilized to investigate the effect of FIZZ1 on cell proliferation. Transwell assay was used to evaluate cell migration, and angiogenesis assay was used to assess cell angiogenesis. Results: FIZZ1 treatment significantly downregulated the expression levels of angiogenesis-inhibiting genes such as Collagen Type I Alpha 1 Chain (COL1A1) and Endothelin Receptor Type A (EDNRA) while upregulated the expressions levels of angiogenesis-promoting genes including Fms Related Receptor Tyrosine Kinase 4 (FLT4) and Integrin Subunit Alpha 3 (ITGA3) (p < 0.05, and p < 0.01). Furthermore, FIZZ1 treatment substantially increased the proliferation, migration, and angiogenesis of aortic endothelial cells (p < 0.05, p < 0.01, and p < 0.001). Additionally, FIZZ1-induced DEGs were associated with crucial cellular functions which positively participate in cell proliferation, migration, and angiogenesis. Conclusion: In summary, FIZZ1 treatment can promote the proliferation, migration, and angiogenesis of aortic endothelial cells. Furthermore, it can induce numerous differentially expressed genes involved in angiogenesis-related functions or pathways. Consequently, FIZZ1 promotes the angiogenesis of aortic endothelial cells, thereby contributing to the progression of atherosclerosis. Therefore, FIZZ1 can serve as a potential therapeutic target for ameliorating atherosclerosis
Berberine against Chronic Atrophic Gastritis by Inhibiting the SDF-1α and p-NF-κB Signaling Pathways
No full textBackground: Chronic atrophic gastritis (CAG) is a prevalent gastrointestinal disorder characterized by gastric inflammation and epithelial cell impairment. Berberine, renowned for its potent anti-inflammatory, antioxidant, and immunomodulatory properties, is frequently utilized in managing gastrointestinal disorders and chronic inflammatory conditions. This study aimed to investigate the protective effects of berberine against CAG in mice and its underlying molecular mechanisms. Methods: CAG was induced in mice through Helicobacter pylori (Hp) infection and ethanol administration. Subsequently, mice were treated with varying doses of berberine (10 and 50 mg/kg). The therapeutic efficacy of berberine was evaluated by analyzing histopathological alterations, serum inflammatory markers, and oxidative stress levels. Moreover, the expression levels of stromal cell-derived factor-1 alpha (SDF-1α), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and proteins related to the nuclear factor-kappa B (NF-κB) signaling pathway were examined through Western blot analysis and immunohistochemistry. Results: Compared to the CAG group, berberine treatment can significantly improve CAG-related histopathological changes, reduce inflammatory infiltrating cells, and reduce gastric gland atrophy and epithelial cell damage. Berberine administration also reduced the levels of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and cyclooxygenase-2 (COX2) compared to the CAG group. Additionally, berberine downregulated the expression of SDF-1α, CXCR4, VEGF, and NF-κB p65 in gastric tissue, suggesting its inhibitory effect on these signaling pathways. Conclusion: This study demonstrates that berberine exerts protective effects against CAG in mice by suppressing the SDF-1α-CXCR4-VEGF and NF-κB signaling pathways. These findings underscore the potential utility of berberine in managing CAG and provide a basis for further investigation into its clinical applicability