Asia Pacific Academy of Science Pte. Ltd.
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Preoperative High Serum Glutamate Dehydrogenase Level can Predict Recurrence of Hepatitis B Virus-Related Hepatocellular Carcinoma
No full textBackground: High glutamate dehydrogenase (GLDH) levels are associated with hepatocellular carcinogenesis. This study investigated the value of preoperative serum GLDH levels in predicting postoperative recurrence in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: In total, 176 patients with HBV-related HCC who underwent hepatectomy were retrospectively evaluated. The optimal GLDH cut-off value to predict recurrence was determined using the receiver operating characteristic curve (ROC) model. The relationship between GLDH level and clinicopathological markers was investigated. Finally, risk variables for tumor recurrence were identified, and the value of GLDH level in predicting disease-free survival (DFS) of patients was evaluated. Results: The optimal cut-off value of GLDH level was 11.2 U/L (area under the curve, 0.676;95% confidence interval, 0.597–0.754), which was used to divide patients into high (>11.2 U/L) and low (≤11.2 U/L) GLDH groups. High GLDH levels were associated with older age, multiple tumors, larger tumor diameter, higher alpha-fetoprotein (AFP) levels, vascular invasion, higher alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and advanced Barcelona Clinic Liver Cancer stage (all p < 0.05). High GLDH (>11.2 U/L) was an independent predictor of DFS (p < 0.001). Furthermore, the 1-, 2-, and 3-year DFS rates in patients with GLDH >11.2 U/L were significantly shorter than those in patients with GLDH ≤11.2 U/L (35.6%, 13.3%, and 10.0% vs. 74%, 56.5%, and 47.2%, p < 0.001). A sensitivity analysis of patients divided into high (>6.25 U/L) and low (≤6.25 U/L) GLDH groups according to the median GLDH value was also conducted, and the results were consistent with the main analyses. Conclusions: GLDH might be a potential recurrence predictor in HBV-related HCC patients undergoing hepatectomy
Investigation of Potential Immune Regulators of Bordetella Pertussis Infection through WGCNA Analysis
No full textBackground: Pertussis is an acute respiratory infectious disease caused by Bordetella pertussis. Over the past decade, the rising incidence of pertussis in many countries, including China, has attracted great attention globally. Methods: Current research focuses on the underlying immune mechanisms of cells in response to pertussis infection and to perform a further analysis and interpretation. A sequencing dataset of human airway epithelium cells infected with B. pertussis was collected from the GEO (Gene Expression Omnibus) database, and transcriptome analysis was subsequently performed. Results: After analysis of differentially expressed genes (DEGs), a total of 149 DEGs were obtained, including 109 down-regulated genes and 40 up-regulated genes. Most were enriched in antigen processing and presentation, endocytosis, toxoplasmosis, and natural killer cell mediated cytotoxicity. WGCNA (weighted correlation network analysis) was also performed and the genes were grouped into different modules as per the corresponding expression trends, among which the yellow, purple and royalblue gene modules indicated a positive correlation with the grouping. Further enrichment analysis and PPI (protein-protein interaction) analysis of the DEGs in the yellow module indicated that CD74, CD274, PDCD1LG2, integrin subunit alpha M (ITGAM) and PTPN22 played a role in the infected cells by B. pertussis. Conclusions: This study collected pertussis sequencing datasets using the GEO database, and analyzed the underlying immune mechanism of pertussis-infected cells, and provided a theoretical basis for mining potential regulatory factors and improving the immune efficacy of vaccines
A Weighted Gene Co-Expression Network Analysis for Identifying Hub Genes in Preeclampsia-Induced Intrauterine Growth Restriction
No full textAim: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are two significant obstetrical diseases that cause serious harm to maternal and infant health. Worldwide, PE is the most frequent cause of IUGR;The latter is regarded as a serious complication of PE but its underlying mechanism and molecular biological changes are poorly understood. Thus, few effective medical therapies for its treatment are available. PE and IUGR share the same etiological background but their connections at the molecular level were rarely known. Consequently, it is of urgency to create an effective method to evaluate their molecular signature. The objective of this study was to identify the hub genes related to PE with IUGR (PE-IUGR) by conducting a weighted gene co-expression network analysis (WGCNA). Methods: The GSE147776 data set containing 28 samples of placental tissue (n = 6 with PE-IUGR) was downloaded from the Gene Expression Omnibus database. The gene expression profile was correlated with phenotypic data and analyzed using a WGCNA. Additionally, a WGCNA was used to construct a gene co-expression network, and hub genes were further identified by identifying modules related to the clinical traits of PE-IUGR. Results: Nine genes, i.e., TDRKH, XPOT, AMACR, NBN, ALS2, CLYBL, CENPQ, PCGF6 and COQ3 were obtained by the WGCNA. These were considered the key genes that were likely involved in IUGR in PE. Conclusions: We constructed a co-expression network of PE-IUGR and identified 9 hub genes related to the condition
Continuous Positive Airway Pressure Effect on the Changes of Regional Brain Activity in Patients with Severe Obstructive Sleep Apnea-Hypopnea Syndrome
No full textObjective: This study aimed to evaluate the effect of continuous positive airway pressure (CPAP) effect on the cognitive function in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods: Twenty-four severe OSAHS patients diagnosed by polysomnography (PSG), and twenty-two healthy adults were included. OSAHS group underwent Epworth Sleepiness Scale (ESS), Montreal Cognitive Assessment (MoCA) score, and resting-state functional magnetic resonance imaging (rs-fMRI) scan before and after CPAP therapy. A statistical map of different brain regions of regional homogeneity (ReHo) was obtained by rs-fMRI images process with Matlab. Cognitive function brain areas in patients with OSAHS were assessed by evaluating changes of cognitive function and neurological function imaging to evaluate the clinical efficacy of CPAP. Results: Compared with the healthy control group, the apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and ESS score were significantly increased, while the lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2) and MoCA score were significantly decreased (p < 0.05) before treatment in OSAHS group. In OSAHS group, AHI, ODI and ESS scores after CPAP treatment were significantly lower than before treatment, while LSaO2, MSaO2 and MoCA scores were significantly higher than before treatment (p < 0.05). ESS scores in OSAHS group were significantly positively correlated with AHI (r = 0.687, p < 0.05) and ODI (r = 0.541, p < 0.05), and MoCA scores were significantly negatively correlated with AHI (r = –0.801, p < 0.05) and ODI (r = –0.783, p < 0.05). The ReHo values of the right angular gyrus, right precuneus, left parahippocampal gyrus, and left middle frontal gyrus were reduced in the OSAHS group at baseline compared to the healthy control group, while the ReHo values in the right posterior lobe of the cerebellum increased. The ReHo value of the right posterior cerebellar lobe in the OSAHS group and the healthy control group was positively related to the MoCA score (r = 0.324, p < 0.05). The ReHo value of the right precuneus before and after CPAP treatment in the OSAHS group was positively related to AHI (r = 0.478, p < 0.05) and negatively correlated to the MoCA score (r = 0.484, p < 0.05). Conclusions: Patients with severe OSAHS generally have cognitive dysfunction, and the structure and function of several brain regions have abnormal changes. After CPAP intervention for 3 months in patients with severe OSAHS, the neural activities of the left limbic lobe, right temporal lobe, posterior cingulate gyrus, and precuneus were increased. Changes in brain activity in these regions may be the neural functional basis for the emergence of cognitive function
Overexpression of SPAG5 Drives In-Vitro Endometrial Cancer Progression via Activating the PI3K/AKT Pathway
No full textBackground: Though sperm-associated antigen 5 (SPAG5) is highly expressed during the tumorigenesis and progression of various cancers, the impact of SPAG5 upon the most prevalent gynecologic cancer, endometrial cancer (EC), remains undefined. This study aims to investigate the impact of SPAG5 on EC cells. Methods: SPAG5 expression in EC tissues and its correlation with the overall survival of EC patients were inspected by bioinformatics. Exogenously upregulating or downregulating SPAG5 expression in EC cells was realized via transfection. Examination of EC cell viability, invasion, migration and apoptosis was accomplished by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Transwell and scratch assays and flow cytometry. Western blot and quantitative real-time polymerase chain reaction were used to measure the expression levels of SPAG5 and mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) pathway-associated proteins and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-linked markers in EC cells. Results: High expression pattern of SPAG5 was observed in EC tissues (p < 0.05) and cells (p < 0.001), and was associated with a shorter survival time of EC patients. SPAG5 expression was successfully upregulated and downregulated via transfection with SPAG5 overexpression plasmid and shSPAG5, respectively (p < 0.01). Overexpression of SPAG5 increased the viability, migration, and invasion, reduced the apoptosis, and elevated the levels of phosphorylated (p)-AKT, p-PI3K, p-AKT/AKT and p-PI3K/PI3K. SPAG5 downregulation resulted in the opposite results (p < 0.05). However, changes in SPAG5 expression were not correlated with the level of p-ERK or ERK. Conclusion: Overexpression of SPAG5 drives in-vitro EC progression via activating the PI3K/AKT pathway
Genetic Polymorphisms of HPA 1–6, 15 Systems in the Hangzhou Population and Their Role in the Management of Platelet Transfusion Refractoriness
No full textBackground: The roles of human platelet antigens (HPAs) in the occurrence and management of platelet transfusion refractoriness (PTR) are still unclear. It is helpful to investigate the local genetic polymorphisms of HPAs and to evaluate the method of antigen match-compatible platelet transfusion aiming to mitigate platelet transfusion refractoriness. Methods: Polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) was used to perform genotyping of the HPA 1–6, 15 systems in 400 platelet donors and 60 patients with positive platelet antibody screening results, and to analyze the effect of matched platelet transfusion in those patients. Results: In the HPA 1–6, 15 systems, allele “b” of HPA-3 was found to have the highest frequency of 0.51, and HPA-15 has the highest heterozygosity of 0.33. The rest HPA systems were dominated by “aa” homozygotes with over 90% genotype frequencies. The results of corrected count increment (CCI) in the antigen match-compatible transfusion group were significantly better than those in the random donor transfusion group (p < 0.05). Inside the match-compatible transfusion group, there was a difference between the cross-match-compatible transfusion group and the gene-match-compatible transfusion group, but no statistical significance (p > 0.1). Conclusions: The prevalence of HPAs in the local population is crucial in the understanding and management of platelet-related clinical disorders. According to the devised matching rules, a local database of platelet genes should be established to provide compatible platelet products to the alloimmunized patients. The safety and efficacy of platelet transfusion are expected to be improved, and in-depth research into blood transfusion can be advanced
Mechanisms of in Vitro Chondrogenic Differentiation of Human BMSCs Induced by Piperlongumine
No full textBackground: Piperlongumine (PL) regulates the production of cellular reactive oxygen species (ROS), and ROS can affect the differentiation of mesenchymal stem cells. In order to add to the medicinal value of PL, this study aimed to explore whether and how PL induces chondrogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs). Methods: To determine the PL concentrations for drug intervention, BMSCs were exposed to varying concentrations of PL, the effects on cell viability were measured by Cell Counting Kit (CCK)-8. After the IC50 (intervention concentration) of PL was determined, the BSMCs were analyzed for changes in morphology (microscopy), degree of chondrogenic differentiation (Alcian blue staining), oxidative stress levels (reactive oxygen species (ROS) assay) and mRNA and protein expressions (quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot) at varying times of treatment. To prove the reliability of the results, the effects of PD98059, an extracellular-signal-regulated kinase (ERK)1/2 inhibitor, and N-acetylcysteine (NAC), an inhibitor of ROS production were also studied. Results: The IC50 of PL was <50%, when PL concentration was greater than 5 μmol/L (p < 0.001) and 5 μmol/L PL used in subsequent experiments. PL promoted the chondrogenic differentiation of BMSCs and increased glycosaminoglycan deposition and ROS production (p < 0.001). At the molecular level, PL increased the expressions of chondrogenic differentiation-related genes and activated the phosphorylation of ERK1/2 (p < 0.001). These effects of PL were partially prevented by NAC (p < 0.01). PD98059 exerted similar effects as NAC (p < 0.001) but did not affect ROS production. Conclusions: ROS and ERK1/2 pathway may be part of the mechanism by which PL enhances chondrogenic differentiation of BMSCs
Tauroursodeoxycholic Acid Attenuates Apoptosis Mediated by High-Concentration Glucose in Proximal Tubular Cells
No full textBackground: Tauroursodeoxycholic acid (TUDCA) treatment significantly decreases the blood sugar content and exerts renoprotective effects in db/db mice. These changes are likely related to endoplasmic reticulum (ER) stress and apoptosis inhibition. Purpose: To elucidate the mechanism underlying the association between the renoprotective effect of TUDCA and ER stress inhibition. Methods: Renal proximal tubular cells (HK-2 (Human Kidney-2) cells) were cultured with or without TUDCA (0.1, 0.2, and 0.4 mmol/L) in normal or high-concentration glucose (HG) media. After 48 h, we determined the HK-2 apoptosis and proliferation rates by flow cytometry and methyl thiazol tetrazolium (MTT) assay, respectively. Furthermore, we detected intracellular reactive oxygen species (ROS) levels and the mitochondrial membrane potential per group. Finally, we analyzed the expression of ER stress-related markers using western blotting and real-time polymerase chain reaction. Results: TUDCA treatment protected HK-2 cells from HG damage, reduced apoptosis, and restored cell proliferation inhibited by HG through the ER stress pathway. The protective effect on HK-2 cells corresponded with ROS inhibition and mitochondrial membrane potential stabilization. Additionally, TUDCA treatment downregulated CCAAT enhancer binding protein (C/EBP) homologous protein (i.e., CHOP) and glucose-regulated protein: 78 kDa (i.e., GRP78) expression, which were upregulated in the HG group. Conclusions: Our results suggest that TUDCA protected renal proximal tubular cells against HG-induced apoptosis by suppressing ER stress
Pre-Clinical Safety Profile and Behavioral Effects of Helicteres isora Linn in an Animal Model
No full textBackground: Helicteres isora is a highly valued medicinal plant whose fruits have been traditionally used throughout Asia, Africa, and other parts of the world in treating a variety of diseases, including diabetes mellitus and memory-related health problems. This study aimed to evaluate the in-vitro/in-vivo toxicity and anti-amnesiac profile of Helicteres isora (H. isora) extract. Methods: Initially, experimental animals were subjected to acute, sub-chronic, and chronic toxicity evaluation to establish the safety profile of the H. isora-crude (Hi-Crd) extract of selected plant fruit extract. In the first phase, oral administrations of the graded doses of 500, 1000, and 1500 mg/kg body weight (b.w.) were administered to experimental rats for 14 days. In the second phase, higher doses (3000, 4000, and 5000 mg/kg b.w.) were administered to assess acute toxicity. On the 28th day, blood was obtained and subjected to serum biochemical analysis and lipid profiling to evaluate chronic toxicity. To further evaluate the toxicity in deep, histopathology studies of the kidney, liver, and pancreas were performed. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the extract were also performed, and IC50 values were calculated. The scopolamine-induced amnesic mice were utilized in behavioral studies (Y-maze and Novel Object Recognition Test (NORT)), where doses of 75 and 150 mg/kg b.w. of Hi-Crd were administered to experimental animals. Results: In the acute toxicity test, no symptoms of morbidity or toxicity were observed. Hi-Crd increased the relative liver and kidney weight at the end of the sub-chronic toxicity test when given at a dose of 4000 mg/kg b.w.. During the chronic toxicity test, the extract showed substantial effects on several biochemical parameters. Although a rise in the lipid profile was noted, the overall effect on other biochemical parameters was negligible. At day 28, there was no significant effect on the liver enzyme markers, and thus the extract was considered to be safe at tested doses. Hi-Crd has a safe profile in terms of uric acid, bilirubin, and blood urea while there was a slight rise in the serum creatinine level. The H.isora-chloroform fraction (Hi-Chl) showed maximum activity with IC50 values of 54.29 ± 1.17 μg/mL against AChE and 105.66 ± 2.91 μg/mL against BuChE. In behavioral studies, the chloroform extract considerably enhanced spontaneous alteration performance as measured through the Y-maze test (p < 0.001), at tested doses. Its counterpart, the ethyl acetate fraction, also showed noteworthy outcomes with good significance levels; p < 0.01 and p < 0.001 at 75 and 150 mg/kg b.w., respectively. In addition, the chloroform fraction significantly improved the discrimination index (DI) in experimental mice to 67.08% as compared to the amnesic group (29.87%) mice results. Conclusions: Helicteres isora Linn was found to be well tolerated during the performed set of tests and could be considered an effective treatment to enhance memory impairment in short- and long-term therapy with an adequate margin of safety. However, the study found that it may have adverse effects to an imperceptible level on kidney and liver functions. Therefore, further studies on other animal models are necessary to confirm its future use as a drug
TRIM27 Promotes the Progression of Laryngeal Cancer by Activating the IL-6/JAK-STAT Signaling Pathway
No full textBackgrounds: Laryngeal cancer manifests as a malignant tumor, often leading to unfavorable prognosis for patients. There is a pressing need for potential biomarkers and therapeutic targets for laryngeal cancer. Our study delved into the role of tripartite motif-containing 27 (TRIM27) in laryngeal cancer cells and studied the effect of interleukin-6 (IL-6) coupled with janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway on the pathogenesis of laryngeal cancer. Methods: Initially, using the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we investigated the expression levels of TRIM27 in both normal epithelial cells (NP69) and laryngeal cancer cells (Hep2). Subsequently, the effects of TRIM27 on IL-6 inflammatory factors and JAK-STAT pathway-associated proteins were measured using enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. Finally, the mechanism of TRIM27 on the growth and metastasis of Hep2 cells was assessed through cell counting kit 8 (CCK8), flow cytometry, and transwell assays. Results: Compared to the normal epithelial cell NP69, TRIM27 levels in the laryngeal cancer cell Hep2 were markedly increased (p < 0.001). TRIM27 overexpression has increased IL-6 levels, activated the JAK-STAT pathway, and increased p-JAK2 and p-STAT3 protein levels. Conversely, silencing TRIM27 inhibited the proliferation and metastasis of Hep2 cells by blocking the JAK-STAT pathway, especially when compared to overexpressing TRIM27 (OE-TRIM27) (p < 0.001). Conclusions: This study demonstrates that silencing TRIM27 can effectively inhibit the progression of laryngeal cancer cells through the deactivation of the IL-6/JAK-STAT pathway, indicating that TRIM27 may be a promising target for laryngeal cancer treatment