Asia Pacific Academy of Science Pte. Ltd.
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Olea europaea Leaf Extract: Antioxidant Properties and Supplement in Human Sperm Cryopreservation
No full textBackground: Semen handling and cryopreservation increase reactive oxygen species (ROS) production, exposing spermatozoa to oxidative stress (OS) that can be minimised by antioxidant supplementation. We studied if Olea europaea leaf extract (OE) could have antioxidant and protective activity during sperm manipulation. Methods: The extract was characterized by high-performance liquid chromatography with diode array detection (HPLC-DAD) and antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays. Then, spermatozoa of 35 normozoospermic donors were treated with OE. First, swim-up selected spermatozoa were incubated with OE (1:100–1:400) and sperm motility and DNA integrity (acridine orange test) were assessed. Then, swim-up selected sperm were treated with 100 μM H2O2 to induce OS with and without OE; motility, DNA integrity and F2-Isoprostanes (F2-IsoPs quantified by gas chromatography/negative ion chemical ionization tandem mass spectrometry analysis), an OS marker, were assessed. Finally, sperm were frozen with and without OE. Beside the previous endpoints, acrosome shape was evaluated by Tetramethylrhodamine (TRITC)-conjugated Pisum sativum agglutinin (PSA). Results: OE was enriched in polyphenols (0.34%) and triterpenes (0.72%) and the synergistic action of phytocomplex components was responsible for antioxidant activity. Since OE was not toxic for spermatozoa, 1:100 dilution was used for the other experiments. OE protected motility, DNA integrity and reduced F2-IsoPs (p < 0.001) in in vitro experiment with OS induction. OE treated frozen-thawed spermatozoa showed increased motility, DNA integrity, reduced F2-IsoP concentration (p < 0.001) and normal acrosomes versus non-supplemented samples. Conclusions: OE is characterized by high concentration of polyphenols and exhibits protective properties against oxidative damage induced by H2O2 in human ejaculated sperm. After cryopreservation, the samples supplemented with the extract showed increased sperm quality. OE could represent a supplement of culture media during semen handling where OS is exacerbated
RUNX1 Inhibites NF-κB/IL-6 Signaling to Promote Bone Remodeling and Suppress Bone Resorption in Mice with Juvenile Ischemic Osteonecrosis
No full textBackground: Previous studies have identified the role of Runt-related transcription factor 1 (RUNX1) in enhancing bone formation by promoting both chondrogenesis and osteogenesis. However, its precise function in juvenile ischemic osteonecrosis (JIO) remains unclear and needs more comprehensive investigation. This current research aims to determine the influence of RUNX1 and the mechanisms on JIO. Methods: Immature C57BL/6 male mice were randomly divided into 4 groups: the Sham, the Osteonecrosis, the Osteonecrosis+negative control (NC), and the Osteonecrosis+RUNX1 groups. Mice in Sham group underwent a sham operation. In Osteonecrosis group, JIO mouse model was established. In Osteonecrosis+NC or Osteonecrosis+RUNX1 group, JIO mouse model was treated with empty lentivirus or RUNX1 overexpression lentivirus. The femoral head tissues of the JIO mice were then evaluated for histopathological changes through hematoxylin-eosin staining. Additionally, the articular chondrocyte necrosis and glycosaminoglycan accumulation in the articular cartilage were examined using Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining and safranin O-fast green staining. The expressions of proteins related to the nuclear factor-kappa B (NF-κB)/interleukin 6 (IL-6) signaling and related to bone remodeling and resorption in the femoral head tissues of the JIO mice were quantified by western blot. Results: Our findings demonstrate that long-term treatment with RUNX1 alleviated femur osteonecrosis in JIO mice. The same treatment relieved articular chondrocyte necrosis and enhanced glycosaminoglycan accumulation in the articular cartilage (p < 0.01). Significantly, treatment with RUNX1 impeded the activation of NF-κB/IL-6 signaling, upregulated the expression of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), and downregulated the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratios in the femoral head tissues of the JIO mice (p < 0.001). Conclusions: RUNX1 blocked NF-κB/IL-6 signaling to promote bone remodeling and suppress the bone resorption in JIO mice. These findings provide a new theoretical framework for further research and potential therapeutic strategies in JIO treatment
Association between Matrix Metalloproteinase 1, 2, 3, and 7 Gene Polymorphisms and Susceptibility to Cervical Cancer: A Meta-Analysis
No full textObjective: This meta-analysis aimed to study the correlation between four polymorphisms in the matrix metalloproteinase (MMP) gene and risk of cervical cancer. Methods: Eligible studies were retrieved from PubMed, Cochrane Library, and Embase. Case-control studies that focused on polymorphic loci rs1799750 in MMP-1, rs243865 in MMP-2, rs3025058 in MMP-3, and rs11568818 in MMP-7 were included in the meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the effects of interest. Quality assessment, heterogeneity analysis, publication bias evaluation, and sensitivity analyses were performed to confirm the reliability of this meta-analysis. Results: Nine studies with 3790 subjects were included. There was significant heterogeneity for rs11568818 GA vs. AA, rs3025058 5A6A vs. 6A6A, and all genetic models of rs243865. There were significant differences in rs11568818 G vs. A (OR [95% CI]: 1.3059 [1.1484;1.4851], p value < 0.0001), GG vs. AA (OR [95% CI]: 1.6884 [1.2912;2.2078], p value: 0.0001), GG vs. AA+GA (OR [95% CI]: 1.6884 [1.2912;2.2078], p value: 0.0001), and GG+GA vs. AA genotype (OR [95% CI]: 1.3805 [1.1459;1.6632], p value: 0.0007);And rs3025058 5A vs. 6A (OR [95% CI]: 1.2078 [1.0379;1.4056], p value: 0.0147), 5A5A vs. 6A6A (OR [95% CI]: 1.4787 [1.0876;2.0103], p value: 0.0126), and 5A5A+5A6A vs. 6A6A (OR [95% CI]: 1.2747 [1.0104;1.6081], p value: 0.0406). There was no significant difference in any of the genetic models for rs1799750 and rs243865. No publication bias was observed in any of the genetic models. Conclusions: MMP-7 rs11568818 G/A and MMP-3 rs3025058 5A/6A were significantly associated with cervical cancer susceptibility
Upregulation of Circulating MiR-211 and MiR-744 is Related to Postpartum Depression via Estrogen Receptor 1 Targeting
No full textBackground and Objective: Postpartum depression (PPD), a severe psychiatric disorder, affects more than 10% of women worldwide. Traditional screening for depression cannot identify patients without a history of mood disorders. This study aimed to identify new candidate biomarkers in exosomes isolated from peripheral blood and explore their function in patients with PPD. Methods: Forty-four patients with PPD and 20 healthy controls were recruited fofr plasma collection. Isolation of extracellular vesicles (EVs) was confirmed by immunoblotting and transmission electron microscopy. Five candidate miRNAs in exosomes were quantified using quantitative reverse transcription PCR (RT-qPCR). Genes repressed by the miRNAs (microRNAs) were identified using a luciferase assay. Results: The levels of miR-211 and miR-744 in plasma exosomes were significantly upregulated in patients with PPD. MiR-211 interacted with the mRNAs of estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2), and repressed their expression. miR-744 can inhibit ESR1 expression but not that of ESR2. Upregulation of miR-211 and miR-744 inhibited estradiol (E2) signaling and repressed the expression of downstream genes including brain-derived neurotrophic factor (BDNF) and cyclin D1 (CCND1). Bioinformatic analysis indicated that 85 genes were directly targeted by both miR-211 and miR-744. These potential target genes were enriched in neuron differentiation, nervous system, and miRNA function. ESR1, SRY-box transcription factor 11 (SOX11), BDNF, EPH receptor B2 (EPHB2), and argonaute 3 (AGO3) were the hub genes in the gene ontology map. Conclusions: The expression of miR-211 and miR-744 was upregulated in exosomes from patients with PPD, which may contribute to the development of PPD by targeting ESR1 and ESR2
High Expression of Polycomb Chromobox 4 in Stomach Adenocarcinoma Promotes Chemotherapy Resistance
No full textBackground: Polycomb chromobox 4 (CBX4) is a component of the polycomb complex and also a small ubiquitin-related modifier E3 ligase. CBX4 has been identified as a poor prognostic marker for various cancers, but its role in stomach adenocarcinoma (STAD) chemotherapy resistance remains unclear. Purpose: The aim of this study was to study the expression of CBX4 in STAD and its role in STAD chemotherapy resistance. Method: This study looked for CBX4 expression level in patients with STAD and adjacent normal tissues by immunohistochemistry generated CBX4 knockout (KO) STAD cell line with CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 technology, checked for CBX4-related transcriptional profile with RNA (Ribonucleic Acid)-seq technology and measured chemotherapy resistance with CCK8 (Cell Counting Kit-8) assay. Result: In this study, CBX4 was found to be highly expressed in STAD tumor tissues. CBX4-related transcriptional profile was illustrated in CBX4 KO STAD cell lines, showing that CBX4 regulated the alternative splicing involved in DNA (DeoxyriboNucleic Acid)-repair pathways. CBX4 KO STAD cells were found to be more vulnerable to 5-fluorouracil (5-FU) treatment. Conclusions: This study confirmed the high expression of CBX4 level in STAD tissues and revealed that CBX4 is a potential biomarker for predicting 5-FU sensitivity in STAD. Inhibition of CBX4 is a potential strategy to overcome the drug resistance of 5-FU in STAD treatment
Prognostic Value of Lactate Dehydrogenase-to-Lymphocyte Ratio in Limited-Stage Small Cell Lung Cancer
No full textBackground: The lactate dehydrogenase (LDH)-to-lymphocyte ratio (LLR) is a simple, non-invasive prognostic marker. We aimed to reveal the prognostic role that LLR plays in limited-stage small cell lung cancer (LS-SCLC). Methodology: This study was a retrospective analysis of 497 patients diagnosed with LS-SCLC from 2015 to 2018, pretreated with LDH, and whose absolute lymphocyte counts were recorded. Patients were categorized into two groups based on their LLR scores: high-risk (LLR ≥182) and low-risk (LLR <182). The Kaplan–Meier test was used to plot the survival curve, and the log-rank test helped evaluate the differences in survival between the high- and low-risk groups. Variables associated with overall survival (OS) and progression-free survival (PFS) were assessed using multivariate and univariate analyses. Additionally, the inverse probability of treatment weight (IPTW) and propensity score matching (PSM) methods helped minimize the selection and confounding bias. Results: The high LLR group had 151 patients, and the low LLR group had 346 patients. In the statistical analysis, we found that the patients PFS and OS were significantly decreased in the high LLR group (PFS: 7.85 vs. 10.41 months, p < 0.0001; OS: 13.4 vs. 18.6 months, p < 0.0001). LLR was an independent prognostic factor for OS (hazard ratio [HR]: 0.719; p = 0.004) and PFS (HR: 0.714; p = 0.002). Similar results were obtained after compensating and matching with the IPTW or PSM methods. Conclusion: Pre-treatment LLR is a potential marker against PFS and OS in patients with LS-SCLC
Expression of NLRC4 is Associated with Apoptosis and Immune Infiltration in Lung Adenocarcinoma Cells
No full textBackground: Nucleotide-binding domain leucine-rich family caspase-activation and recruitment domain (CARD) domain-containing protein 4 (NLRC4) has been linked to several human diseases. However, its function in lung adenocarcinoma is uncertain. Methods: NLRC4 expression was investigated using The Cancer Genome Atlas (TCGA) and pan-cancer Genotype-Tissue Expression data. The researchers examined the link between NLRC4 expression and patient outcome by using TCGA clinical survival data. NLRC4 enrichment was analyzed using the clusterProfiler R package. The TCGA database was also used to investigate the association between NLRC4 expression and immune cell infiltration. Western blot was used to confirm NLRC4 expression and its effect on apoptosis-related proteins in lung adenocarcinoma. Immunohistochemistry was used to investigate the effect of NLRC4 expression on immune cell infiltration. Results: NLRC4 expression is low in lung adenocarcinoma. Low NLRC4 expression was associated with related genes involved in apoptosis and immune cell activation. Further investigation showed that low NLRC4 expression was associated with high infiltration scores of macrophages, dendritic cells, T cells, B cells, and natural killer (NK) cells. NLRC4 knockdown inhibited apoptosis-related protein production in lung adenocarcinoma cells. The number of peripheral macrophages, dendritic cells, T cells, B cells, and NK cells was significantly reduced in pathological tissues with low NLRC4 expression. Conclusions: Our findings suggest that NLRC4 may be a risk gene for lung adenocarcinoma and affects the infiltration of the tumor immune cells
Acute and Long-Term Inflammatory Responses in Well-Trained Young Swimmers throughout a Training Season
No full textBackground: The immunological responses to exercise and the corresponding adaptations in high-level sports have become an important issue, from both the health and the physical performance points of view. A better understanding of the immune responses to exercise and chronic exercise training may benefit athletes and improve physical performance and health. The purpose of this study was to investigate the fluctuations in the immune status of young swimmers throughout a training season. Methods: Twelve well-trained male swimmers (14.08 ± 1.0 yrs) were recruited. Measurements were carried out at the beginning of the training season (T1) and pre- and post the taper of each competitive period (i.e., T2, T3 for the first training macrocycle, and T4, T5 for the second macrocycle, respectively). Blood samples were collected before and 1 hour post a maximal 400 m swimming testing at each of the above time points. Serum interleukin (IL)-1β, IL-6, IL-1rα, IL-4, IL-10, C-reactive protein (CRP) and creatine kinase (CK) levels were measured. Adjustment for exercise-induced plasma volume changes was performed before all data analyses. Two-way analysis of variance (ANOVA) with repeated measures was used for statistics. Results: An anti-inflammatory profile was induced during the second competitive period characterized by a reduction in the levels of inflammatory indices (T1 compared to T4 and T5, IL-1β: p = 0.019, p = 0.034 respectively; T1 compared to T4, CRP: –43%, p > 0.05) along with a tendency of increase in anti-inflammatory ones (T1–T5, IL-6: 75%, T4–T5 IL-10: 122%; p > 0.05). Moreover, acute exercise induced anti-inflammatory responses, causing an increase in anti-inflammatory cytokines (IL-6, IL-10, IL-1rα; p < 0.05). There was a significant decrease in serum CK levels between T1-T4 both in the pre- and post-test condition (p = 0.027, p = 0.005, respectively), while significant differences were found between pre- and post-test at T1, T2, and T4 (p = 0.000, p = 0.011, p = 0.017, respectively). Conclusions: The findings of this study indicated that swimming training throughout a season induces mild long-term but strong acute effects on the immune profile of the swimmers. These findings should be taken into consideration throughout a training season in young swimmers, adjusting the exercise stimuli accordingly in terms of volume, intensity, and recovery time
Overexpression of EPB41L3 Enhances the Apoptosis-Promoting Effect of Cis-Dichlorodiammine-Platinum in Esophageal Squamous Cell Carcinoma
No full textObjective: Cis-dichlorodiammine-platinum (CDDP) is an important drug in chemotherapy regimen for esophageal squamous cell carcinoma (ESCC). Unfortunately, CDDP, even at moderate doses, has toxic effects on normal cells and adverse effects in patients. Erythrocyte membrane protein band 4.1-like 3 (EPB41L3) acts as a cancer inhibitor in many cancers by promoting apoptosis and inhibiting tumor cell proliferation. Therefore, we investigated the potential synergistic anti-ESCC effect of EPB41L3 and CDDP for improving effectiveness of CDDP and lowering CDDP dosage. Methods: EPB41L3 expression in ESCC tissues and cells was examined using Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). ESCC cell models were treated with EPB41L3 transfection alone (EPB41L3 group), CDDP (2 μM) treatment alone (CDDP group), or combined EPB41L3 transfection and CDDP treatment (CDDP+EPB41L3 group), respectively. Cell Counting Kit-8 (CCK-8) was used to examine the cell proliferation in each group. The cell viability of each group was evaluated through cell colony assay. Cell apoptosis and cycles were evaluated using flow cytometry. Western blotting was performed to examine the levels of apoptosis-related proteins and cell cycle-related proteins in each group. Results: The expression level of EPB41L3 in ESCC tissues and cells was reduced, compared with control group. ESCC cell proliferation and cell viability in the CDDP+EPB41L3 group were lower as compared to those in EPB41L3 and CDDP groups. The CDDP+EPB41L3 group showed higher levels of apoptosis, Bax proteins and cleaved-Caspase3, whereas lower level of Bcl-2 protein was shown in ESCC cells, as compared to the other two groups respectively. The G2/M phase ratio and p21 protein levels of ESCC cells treated with both EPB41L3 and CDDP were increased as compared to those in the other two groups. In terms of G0/G1 phase ratio and cyclin-dependent kinases (CDK)1, CDK2 and Cyclin B protein levels, the CDDP+EPB41L3 group exhibited much lower levels than those in the other two groups. Conclusions: Overexpression of EPB41L3 increased the apoptosis-promoting effect of CDDP and its blocking effect on ESCC cells in the G2/M phase, by which the effect of CDDP on inhibiting ESCC cell proliferation and cell viability is improved. This study offers new perspectives on the clinical application of CDDP in the management of ESCC when combined with adjuvant therapy
Psychotria Serpens Linn Improves Ankle Traumatic Arthritis by Repressing NF-κB/p38-MAPK Pathway
No full textBackground: This study aimed to evaluate the efficacy of the water extract of Psychotria serpens Linn (PSL) based on a rat model of post-traumatic ankle arthritis (PTAA) and tumor necrosis factor alpha (TNF-α)-induced apoptosis in chondrocytes, and to explore the related therapeutic mechanism based on nuclear factor-kappaB (NF-κB)/p38 mitogen-activated protein kinase (p38-MAPK) pathway. Methods: After the PTAA rat model was successfully established, the rats were randomly divided into 4 groups (n = 4 per group): model group, ibuprofen group, PSL 5 g/kg group and PSL 20 g/kg group. X-ray imaging, hematoxylin and eosin (H&E) staining of ankle joints and modified safranin O-fast green staining and scoring of cartilage were carried out after the operation. Next, C28/I2 chondrocytes were cultured and divided into 5 groups: normal group, TNF-α group, TNF-α+4-Phenylbutyric acid (4-PBA) group (positive control), TNF-α+PSL group (300 μg/mL, 400 μg/mL, 500 μg/mL). The endoplasmic reticulum stress-related apoptosis of C28/I2 chondrocytes was induced by TNF-α. After the treatment of the chondrocytes with water extract of PSL, cell viability was measured by Cell Counting Kit-8 (CCK-8), apoptosis was detected by flow cytometry, and expression of NF-κB/p38-MAPK pathway was detected by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and western blotting. Results: In the in vivo experiments, compared with the model group, H&E staining of the rats ankle joint, and modified safranin O-fast green staining and cartilage scoring (p < 0.05) all showed that PSL improved the PTAA healing in rats. In the in vitro experiments, compared with the TNF-α group, PSL significantly increased cell viability (p < 0.05) and proliferation (p < 0.05) and repressed apoptosis (p < 0.05) in TNF-α-treated chondrocytes and downregulated the expression of the NF-κB/p38-MAPK pathway (p < 0.05). Conclusions: PSL has a significant beneficial effect on traumatic ankle arthritis, the mechanism of which may be related to the repression of the NF-κB/p38-MAPK pathway