Cellular and Molecular Biology

E-selectin is associated with stable angina and myocardial infarction in a sample of Kurdish population

2024-04-22T20:37:57+02:00

Endothelial dysfunction is the main factor that causes the onset of CAD. Leukocyte adhesion to the endothelium of the active blood artery wall has been demonstrated to be one of the early indicators of arteriosclerosis. This process is regulated by selectins. The purpose of this study is to ascertain the relationship between the polymorphisms in the E-selectin gene that have been linked to ischemic heart disease. We looked at the functional impact of the E-selectin gene polymorphism 7170G>C in Iraqi patients with IHD. This study was conducted on 200 participants who were admitted to the surgical specialty hospital-cardiac center in Erbil City, Iraq between October 2021 and May 2022. Based on the outcomes of the clinical examination, laboratory tests, coronary angiography (COA), acute myocardial infarction (MI) type ST-elevation myocardial infarction (STEMI), stable angina pectoris (SAP), and healthy control groups were tested. Each sample was subjected to Sanger sequencing. The polymorphism was significantly linked to stable angina and myocardial infarction Genotype CC was higher in SAP when compared with MI and control groups which was statistically significant with (p-value<0.05). A higher proportion of C allele was observed in SAP patients (15.7%) which was significantly higher than MI (14.58%) and control (10.8%). The statistical chi-square analysis for allele G frequency showed insignificant differences (p-value>0.05) between patients and the control group. Genetic variation in E-selectin such as polymorphism in nucleotide 7170 G>C at exon 4 region can significantly affect the outcome of cardiovascular diseases.

Association of IL-1β 542 T>A gene polymorphism with Recurrent Aphthous Stomatitis in Erbil City population

2024-04-22T20:37:58+02:00

Recurrent Aphthous stomatitis (RAS) is common oral mucosal condition. The pathophysiology of RAS is affected by a variety of variables, including microbial, genetic, immunological and local and systemic diseases. Interleukin IL-1β, a cytokine that promotes inflammation, has been found in high concentrations in the circulation of RAS. The goal of current investigation was to determine whether RAS is connected with polymorphisms of the IL-1β 542 T>A gene. A total of 60 RAS patients and 30 controls were included in the study. Biochemical investigations for determining (vitamin D, vitamin B12 and zinc) were done and genotypes of IL-1B gene polymorphisms were determined using polymerase chain reaction (PCR) and sequencing. The mean age of the participants was 30.83 ± 1.466 years (range 16 to 50). There was no significant association of SNP IL-1β 542T>A polymorphism with RAS diseases compared to controls, in both parameters such as sex (p-value=0.495) and age groups (p-value=0.6253). There was significant difference in the occurrence of both A and T alleles between RAS patients and controls (p-value=0.0058). The mean vitamin D in both genotypes TA and TT differed significantly (p-value=0.007) but in genotype AA there was no significant difference. Significant difference was observed in zinc concentration between patients and controls (p-value=0.0031). The findings of current investigation indicate that there is a specific IL-1β 542 T>A gene variation that is associated to the pathogenesis of RAS. Allele A was related to the risk of RAS in Erbil city population.

The tumor suppressor effect of miRNA 200-c-3p on A549 non-small cell lung cancer cell line is associated with down-regulation of programmed cell death ligand 1; an immune-check point mechanism

2024-04-22T20:37:55+02:00

MiRNA 200-c-3p has varying functions in different tumor types, whether tumor suppression or promotion. Comprehensive assessment of its function in non-small cell lung cancer (NSCLC) together with its effect on antitumor immune response have not been declared before. We aimed to explore the effect of replacement and suppression of miRNA 200-c-3p on non-small cell lung cancer and its impact on immune checkpoint function and subsequently antitumor immunity. MiRNA 200-c-3p mimic/inhibitor was transfected into the A549 cells. A 549 non-small cell lung cancer cells viability was done by trypan blue staining and 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flowcytometric analysis was done for apoptosis detection. Real‐time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to study its effect on relative gene expression and relative protein level of programmed cell death ligand 1 (PD-L1). Finally, co-culture with isolated and activated T cells was performed. Multiple comparisons were performed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple-comparison test. Decreased cell viability, increased apoptosis, reduced PD-L1 relative gene expression and its relative protein level, together with enhanced T cell cytotoxicity towards tumor cells were detected after miRNA 200-c-3p mimic transfection of A549 NSCLC cell line. However, these results were reversed in miRNA 200-c-3p suppression. MiRNA 200-c-3p had a tumor suppressive effect in non-small cell lung cancer cells which might be through down regulation of PD-L1 relative gene expression, and it may be used as a new target to improve immune checkpoint dysfunction.

Effect of NAMPT on the proliferation and apoptosis in odontoblast-like MDPC-23 cell

2024-04-22T20:37:53+02:00

This study aimed to evaluate the physiological role of NAMPT associated with MDPC-23 odontoblast cell proliferation. Cell viability was measured using the (DAPI) staining, caspase activation analysis and immunoblotting were performed. Visfatin promoted MDPC-23 odontoblast cell growth in a dose-dependent manner. Furthermore, the up-regulation of Visfatin promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers in MDPC-23 cells. However, FK-866 cell growth in a dose-dependent manner induced nuclear condensation and fragmentation. FK-866-treated cells showed H&E staining and increased apoptosis compared to control cells. The expression of anti-apoptotic factors components of the mitochondria-dependent intrinsic apoptotic pathway significantly decreased following FK-866 treatment. The expression of pro-apoptotic increased upon FK-866 treatment. In addition, FK-866 activated caspase-3 and PARP to induce cell death. In addition, after treating FK-866 for 72 h, the 3/7 activity of MDPC-23 cells increased in a concentration-dependent manner, and the IHC results also confirmed that Caspase-3 increased in a concentration-dependent. Therefore, the presence or absence of NAMPT expression in dentin cells was closely related to cell proliferation and formation of extracellular substrates.

In vivo determination of the anti-inflammatory and antioxidant effects of the aqueous extract of Syzygium aromaticum (clove) in an asthmatic rat model

2024-04-22T20:37:50+02:00

Asthma is a chronic inflammatory disease of the airways strongly associated with interleukin-4 (IL-4), a cytokine that mediates and regulates various immune responses, including allergic reactions. This study aimed to evaluate the anti-inflammatory and antioxidant effects of an Aqueous Extract of Clove (AEC) Syzygium aromaticum on the lungs and erythrocytes of an experimental asthma model in Wistar rats. For this purpose, four groups of male rats were examined: control, sensitized with ovalbumin (OVA), treated with AEC, and treated with a combination of OVA/AEC. After treatment, the antioxidant effect was determined by measuring the malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) levels. The anti-inflammatory effect was determined by measuring IL-4 levels by performing enzyme-linked immunosorbent assay (ELISA) using serum, lung, and bronchoalveolar lavage fluid (BALF) samples. A significant reduction (p ≤ 0.05) in the MDA levels and a significant increase (p ≤ 0.05) in the levels of GPx and CAT were observed in the lungs of rats treated with cloves. However, no statistically significant variation was observed in GSH levels. In erythrocytes, no statistically significant differences were observed between the experimental batches. Regarding the anti-inflammatory effect, the administration of S. aromaticum extract to sensitized rats resulted in a recovery in the levels of total proteins and IL-4 and a decrease in the three compartments studied (lungs, serum, and bronchoalveolar liquid). These results were confirmed by microscopic examination of lung histological sections. Overall, these findings confirmed that the AEC has anti-inflammatory and antioxidant effects.

Identification of small molecule inhibitors of penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus for the therapeutics of bacterial infection

2024-04-22T20:37:46+02:00

The penicillin binding protein 2a (PBP2a) is a key enzyme associated with bacterial cell wall synthesis and bacterial infection. Therefore, targeting PBPa2 offers a promising approach for the therapeutics of bacterial resistance and infection. This study presents a comprehensive analysis of alpha-mangostin as a potential inhibitor of PBPa2. Molecular docking simulations revealed a strong binding affinity between alpha-mangostin and PBP2a, with an affinity score of -6.01 kcal/mol. Notably, alpha-mangostin formed a preferential hydrogen bond with THR216 of PBP2a, alongside several other polar and hydrophobic interactions. ADME and Toxicity predictions indicated that alpha-mangostin possesses favourable pharmacokinetic properties, suggesting its potential as a therapeutic agent. PASS analysis further highlighted its broad range of favourable biological properties. SwissTargetPrediction analysis reinforced these findings, indicating alpha-mangostin's association with various biological processes. Cell toxicity assays demonstrated that alpha-mangostin had no significant impact on the viability of HEK-293 cells, suggesting its potential safety for further development. The IC₅₀ value for alpha-mangostin was found to be 33.43µM. Fluorescence-based binding assays showed that alpha-mangostin effectively inhibited PBP2a activity in a concentration-dependent manner, supporting its role as an inhibitor. In conclusion, the results suggest alpha-mangostin as a promising candidate for inhibiting PBP2a. Further, extensive studies are warranted to explore its clinical applications.

MicroRNA-503-5p protects streptozotocin-induced erectile dysfunction in diabetic rats by downregulating SYDE2

2024-04-22T20:37:44+02:00

Plentiful studies have clarified miRNAs take on a key role in the sexual dysfunction of diabetic rats. This study aimed to figure out microRNA (miR)-503-5p/SYDE2 axis’ latent mechanisms in streptozotocin-induced diabetic rat sexual dysfunction. A model of erectile dysfunction (ED) in diabetic rats was established by injecting streptozotocin. MiR-503-5p and SYDE2 in ED rats were altered by injection of miR-503-5p mimic or si/oe-SYDE2. The targeting link between miR-503-5p and SYDE2 was testified. ICP/MAP value was tested by pressure sensor; Penile capillary abundance was assessed; Penile cGMP and AGEs were detected; penile smooth muscle cell apoptosis was assessed; MiR-503-5p and SYDE2 were tested. In streptozotocin-induced ED rats, miR-503-5p was reduced and SYDE2 was elevated. Elevating miR-503-5p or silencing of SYDE2 can enhance penile erection rate, ICP/MAP value, capillary abundance, and cGMP but reduce AGEs and penile smooth muscle cell apoptosis rate in ED rats. Strengthening SYDE2 with elevating miR-503-5p turned around the accelerating effect of elevated miR-503-5p on penile erection in ED rats. SYDE2 was a downstream target gene of miR-503-5p. MiR-503-5p protects streptozotocin-induced sexual dysfunction in diabetic rats by targeting SYDE2.

MiR-4319 targets tuftelin 1 to reduce malignancy of cervical cancer cells

2024-04-22T20:37:45+02:00

Cervical cancer (CC) is the most common malignant tumor of female reproductive system. MiR-4319 has been identified as an anti-oncogene in various cancers. In the present study, role of miR-4319 in CC was identified. Colony formation, flow cytometer, wound healing, and transwell assays were used to detect CC cell proliferation, apoptosis, migration, and invasion. The expression of miR-4319 was decreased in clinical CC tissues and CC cell lines. Upregulation of miR-4319 suppressed cell viability, proliferation, migration, and invasion, and induced cell apoptosis in CC cells. Moreover, tuftelin 1 (TUFT1) was verified as a direct target of miR-4319, as confirmed by dual-luciferase reporter assay. Additionally, TUFT1 expression was remarkably increased in clinical CC tissues and CC cell lines and was negatively associated with miR-4319 expression. Furthermore, overexpression of TUFT1 partially restored the effects of miR-4319 mimic on cell viability, proliferation, migration, invasion, and cell apoptosis in CC cells. To conclude, miR-4319 played an anti-cancer role in the occurrence and development of CC, which might be achieved by targeting TUFT1.

Identification of hub genes and key pathways in spinal cord injury via bioinformatics analysis

2024-04-22T20:37:47+02:00

This study aimed to explore the hub genes and related key pathways in Spinal Cord Injury (SCI) based on the bioinformatics analysis. Two microarray datasets (GSE45006, GSE45550) were obtained from the GEO database and were merged and batch-corrected. The differentially expressed genes (DEGs) in SCI were explored with the Limma, and the weighted gene co-expression network analysis (WGCNA) was conducted to explore the module genes. Functional enrichment analysis and Gene set variation analysis (GSVA) were used to investigate the biological functions and key pathways of the key genes related to SCI. Then the protein-protein interaction (PPI) network was generated using the STING online tool, and the hub genes in SCI were identified. Receiver operating characteristic (ROC) curves were applied to assess the diagnostic value of the selected hub genes. We identified 554 DEGs in SCI, and 1236 key genes in SCI were selected via WGCNA. Totally 111 key genes related to SCI were discovered. Furthermore, the functional enrichment analysis showed that these key mRNAs were primarily enriched in the extracellular matrix (ECM)-related pathways and processes associated with wound healing and cell growth. The PPI network further filtered six hub genes (Cd44, Timp1, Loxl1, Col6a1, Col3a1, Col5a1) ranked by the degree, and the diagnostic value of the six hub genes was confirmed by the ROC curves. Six hub genes including Cd44, Timp1, Loxl1, Col6a1, Col3a1, and Col5a1 were identified in SCI, with differential expression and excellent diagnostic value, which might provide insight into the targeted therapy of SCI.

Antibacterial effect and biocompatibility of silver nanoparticle-coated bone allograft substitutes

2024-04-22T20:37:42+02:00

Osteoinduction, and/or osteoconduction, and antibacterial characteristics are prerequisites for achieving successful bone grafting. This study aimed to coat bone allografts with silver nanoparticles and assess their antibacterial activity and biocompatibility compared to uncoated bone allografts. In this study, the bone allografts were coated with varying concentrations of silver nanoparticles (5 mg/l, 10 mg/l, and 50 mg/l) through a simple adsorption technique. Subsequently, the coated samples underwent characterization using SEM, FTIR, EDS, and XRD. The Minimal Inhibitory Concentration (MIC) of the silver nanoparticles was determined against Staphylococcus aureus and Streptococcus mutans. Bacterial growth inhibition was evaluated by measuring turbidity and performing a disk diffusion test. Moreover, qualitative investigation of biofilm formation on the coated bone allograft was conducted using SEM. Following this, MG-63 cell lines, resembling osteoblasts, were cultured on the bone allografts coated with 5 mg/l of silver nanoparticles, as well as on uncoated bone allografts, to assess biocompatibility. The MIC results demonstrated that silver nanoparticles exhibited antimicrobial effects on both microorganisms, inhibiting the growth of isolates at concentrations of 0.78 mg/L for Staphylococcus aureus and 0.39 mg/L for Streptococcus mutans. The bone allografts coated with varying concentrations of silver nanoparticles exhibited significant antibacterial activity against the tested bacteria, completely eradicating bacterial growth and preventing biofilm formation. The osteoblast-like MG-63 cells thrived on the bone allografts coated with 5 mg/l of silver nanoparticles, displaying no significant differences compared to both the uncoated bone allografts and the control group. Within the limit of this study, it can be concluded that silver nanoparticles have a positive role in controlling graft infection. In addition, simple adsorption technique showed an effective method of coating without overwhelming the healing of the graft.

The relationship between preeclampsia risk and SENCR rs555172 gene polymorphism and expression

2024-04-22T20:37:40+02:00

Preeclampsia, the more severe manifestation of gestational hypertensive disorders, is a major cause of maternal and perinatal morbidity and mortality worldwide. Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic preeclampsia. This study aimed to explore the association between SENCR rs555172 SNP and PE risk in healthy pregnant women compared to women with preeclampsia. A total of 140 healthy pregnant women and 130 preeclampsia cases were included in the study. The rs555172 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of the SENCR gene was analyzed in 40 placenta tissue samples from both groups. Various statistical approaches were employed to assess the genotypic and allelic frequencies. The results showed no significant difference in the frequency of the rs555172 polymorphism between healthy pregnant women and those with preeclampsia in terms of the dominant (p=0.82), recessive (p=0.39), and over-dominant (p=0.42) models. Additionally, the analysis of SENCR relative expression revealed no significant difference between the two groups (p=0.48). In conclusion, the LncRNA SENCR rs555172(G/A) seems not associated with an increased risk of Preeclampsia in pregnant women.

Identification of osteogenic differentiation-related miRNA-mRNA regulatory network of human periodontal ligament stem cells

2024-04-22T20:37:37+02:00

This study aimed to investigate the hub genes and miRNA–mRNA regulatory network around periodontal ligament stem cells (PDLSC) for osteogenic differentiation through bioinformatic analysis. The dataset with osteogenic differentiation of human PDLSC was downloaded from the GEO database. The Weighted gene coexpression network analysis (WGCNA) was performed to identify key modules and hub genes. In addition, differentially expressed genes (DEGs) analysis was conducted with limma. The functional enrichment of differentially expressed hub genes was implemented with KEGG and GSEA analysis. The targeted genes of differentially expressed miRNA were predicted based on miRWalk database. The miRNA-mRNA interaction network of osteogenic differentiation of PDLSC was constructed and visualized. The WGNCA results showed that the light-cyan module was positively correlated with osteogenic differentiation (r=0.98, P<0.05). A total of 3125 hub genes and 1426 differentially expressed hub genes were detected in OG group. Innate immune-related signaling pathways and metabolic pathways were involved in the osteogenic differentiation. In addition, total of 2 upregulated miRNAs with 63 targeted DEGs and 6 downregulated miRNAs with 214 targeted DEGs were detected, which contributed to osteogenic differentiation by regulating amino acid metabolism signaling pathway. We identified hub genes and miRNA–mRNA regulatory network contributing to osteogenic differentiation of human PDLSC, which will provide novel strategy for periodontal disease therapy.

Identification of 10 differentially expressed and cuproptosis-related genes in immune infiltration and prognosis of thyroid carcinoma

2024-04-22T20:37:39+02:00

The association between the cuproptosis-related genes and the immune infiltration and their prognostic value in thyroid carcinoma is still unexplored. Bioinformatics analyses were performed with data obtained from the TCGA dataset. The aberrantly expressed genes were selected. KEGG and GO analyses were conducted to explore the enriched pathways of the up-regulated or down-regulated genes in thyroid carcinoma. Totally 1495 genes were differentially expressed (691 up-regulated, 804 down-regulated) in thyroid carcinoma (p<0.05). The 10 cuproptosis-related RNAs (DLD, LIAS, LIPT1, FDX1, DLAT, MTF1, PDHA1, CDKN2A, GLS and PDHB) were also demonstrated to be aberrantly expressed in thyroid carcinoma patients tissues. FDX1 expression was correlated with the overall survival in thyroid carcinoma patients (HR=0.4995, 95% CI: 0.2688-0.9285, p=0.0282). Further multivariate cox regression analysis revealed that DLD (HR=24.8869, 95% CI: 4.48772-138.01181, p=0.00024), and LIAS (HR=7.74092, 95% CI: 1.12194-53.40898, p=0.03783) were associated with the survival of thyroid carcinoma patients. The immune infiltration analysis demonstrated that significant correlation between the 10 cuproptosis-related genes and immune infiltration in thyroid carcinoma (p<0.01). We presented the expression profiles of dysregulated genes in thyroid carcinoma. The findings of our study highlighted the potential of cuproptosis-related genes as prognostic biomarkers for thyroid carcinoma.

Ginsenoside Rc alleviates osteoporosis by the TGF-β/Smad signaling pathway

2024-04-22T20:37:36+02:00

Osteoporosis is a common chronic bone disorder in postmenopausal women. Ginsenosides are primary active components in ginseng and the effects of various ginsenoside variants in osteoporosis treatment have been widely revealed. We planned to explore the impact of ginsenoside Rc on bone resorption in an osteoporosis rat model. We used ovariectomized rats to assess the potential impact of ginsenoside Rc on osteoporosis. μ-CT was implemented for analyzing the microstructure of the distal left femur in rats. H&E staining together with Masson staining were applied for bone histomorphometry evaluation. ELISA kits were implemented to detect serum concentrations of TRACP-5b, OCN, CTX, as well as PINP. Ginsenoside Rc treatment lessened the serum levels of TRACP-5b as well as CTX, while increasing serum levels of OCN, and PINP of OVX rats. Moreover, we found that ginsenoside Rc contributed to the synthesis of type I collagen via increasing Col1a1 and Col1a2 levels in femur tissues of ovariectomized rats. Our findings also revealed that ginsenoside Rc activated the TGF-β/Smad pathway by increasing TGF-β as well as phosphorylated Smad2/3 protein levels. Ginsenoside Rc alleviates osteoporosis in rats through promoting the TGF-β/Smad pathway.

TNFRSF6 induces mitochondrial dysfunction and microglia activation in the in vivo and in vitro models of sepsis-associated encephalopathy

2024-04-22T20:37:34+02:00

Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis. The tumour necrosis factor receptor superfamily member 6 (TNFRSF6) gene encodes the Fas protein, and it participates in apoptosis induced in different cell types. This study aimed to explore TNFRSF6 function in SAE. The SAE mouse model was established by intraperitoneal injection of LPS in TNFRSF6^−/− mice and C57BL/6J mice. Microglia were treated with LPS to establish the cell model. The learning, memory and cognitive functions in mice were tested by behavioral tests. Nissl staining was utilized for determining neuronal injury. Microglial activation was tested by immunofluorescence assay. ELISA was utilized for determining TNF-α, IL-1β, IL-6, and IL-10 contents. Mitochondrial dysfunction was measured by mitochondrial oxygen consumption, ATP content, ROS production, and JC-1 assay. TNFRSF6 was upregulated in the LPS-induced mouse model and cell model. TNFRSF6 deficiency notably alleviated the impaired learning, memory and cognitive functions in SAE mice. Furthermore, we found that TNFRSF6 deficiency could alleviate neuronal injury, microglial activation, and inflammation in SAE mice. Additionally, mitochondrial dysfunction in the SAE mice was improved by TNFRSF6 depletion. In the LPS-induced microglia, we also proved that TNFRSF6 knockdown reduced inflammatory response inhibited ROS production, and alleviated mitochondrial dysfunction. TNFRSF6 induced mitochondrial dysfunction and microglia activation in the in vivo and in vitro models of SAE.

Development of a novel six DNA damage response-related prognostic signature in osteosarcoma

2024-04-22T20:37:31+02:00

DNA damage response (DDR) plays a vital role in the development of cancer. Nevertheless, in osteosarcoma, the potential of DDR-related genes (DDRGs) remains unclear. Thus, the current research is intended to investigate the mechanisms of DDRGs in the development of osteosarcoma and to explore potential DDR-related biomarkers in forecasting the prognosis of osteosarcoma patients. The osteosarcoma genomic data from TCGA, GEO and cBioPortal databases were utilized for screening and identification of differentially expressed DDRGs (DEDDRGs). Consensus clustering analysis was performed to identify different subtypes of osteosarcoma based on the expressions of DDRGs. Key DEDRRGs were identified by overlapping DEDRRGs between different subtypes and DEDRRGs between tumor and control samples. Univariate, as well as LASSO regressions, were further applied to obtain robust prognostic signatures. GSVA and ssGSEA analysis were implemented to explore the underlying mechanisms of prognostic DDRG signature in regulating osteosarcoma. In addition, the drug sensitivity of patients in low- and high-risk groups was evaluated using pRRophetic algorithm. A total of 43 key DEDRRGs were identified. Followed by univariate Cox along with LASSO regression analyses, CDK6, CSF1R, EGFR, ERBB4, GATA3 and SOCS1 were identified as prognostic signatures in osteosarcoma. Cox regressions revealed that the risk score was an independent prognostic factor in osteosarcoma. DDR may affect osteosarcoma via regulating immune microenvironment along with influencing cell proliferation, migration, adhesion and apoptosis. The chemotherapeutic response between patients in low- and high-risk groups was much different. The role of DDRGs in osteosarcoma and identified six DDR-linked biomarkers for forecasting the prognosis of osteosarcoma patients. Our outcomes enhanced the understanding of DDR-related molecular mechanisms involved in osteosarcoma and provided potential therapeutic targets for osteosarcoma patients.

Comprehensive bioinformatics analysis of KIF20A as a prognosis biomarker for clear cell renal cell carcinoma

2024-04-22T20:37:27+02:00

It has been shown that kinesin family member 20A (KIF20A) is involved in the development of several cancers. However, research on clear cell renal cell carcinoma (ccRCC) and KIF20A is still exploratory. The current research was carried out to determine whether KIF20A expression has any prognosis value in ccRCC. Data were downloaded from The Cancer Genome Atlas (TCGA) database to validate the KIF20A mRNA expression and to perform clinicopathological analysis. Receiver operating characteristic (ROC) curves were used in evaluating KIF20A's diagnostic performance for ccRCC. The prognostic value of KIF20A in ccRCC was estimated by the Kaplan–Meier survival curve and Cox regression analysis. Gene set enrichment analysis (GSEA), functional annotations, and immune infiltration analysis were used to determine the potential mechanism of KIF20A’s role in ccRCC. The increase in KIF20A mRNA expression was associated with sex, clinical stage, histologic grade, and TNM stage. ROC curve indicated that KIF20A could distinguish ccRCC from normal kidney samples. Survival study showed that high KIF20A expression predicted poor ccRCC prognosis. Thus, KIF20A expression could be used as an independent overall survival (OS) risk factor for ccRCC patients. Co-expression analysis identified TPX2 as a strong, positively correlated factor with KIF20A in ccRCC. Functional enrichment analyses and GSEA showed that KIF20A and TPX2 participated in various tumor-related pathways. Moreover, KIF20A and TPX2 expression were significantly associated with the level of immune infiltration into ccRCC. KIF20A may be a therapeutic target and a prognostic biomarker for ccRCC.

ATF3/EGR1 regulates myocardial ischemia/reperfusion injury induced autophagy and inflammation in cardiomyocytes

2024-04-22T20:37:16+02:00

Myocardial ischemia/reperfusion injury (MIRI) is an irreversible adverse event during the management of coronary heart disease that lacks effective controls. The underlying mechanism of MIRI still requires further investigation. Recent studies have suggested that overexpression of ATF3 protects against MIRI by regulating inflammatory responses, ferroptosis, and autophagy. The downstream target of ATF3, EGR1, also showed cardioprotective properties against MIRI by promoting autophagy. Therefore, further investigating the effect of ATF3/EGR1 pathway on MIRI-induced inflammation and autophagy is needed. Cardiomyocyte MIRI model was established by challenging H9C2 cells with hypoxia/reoxygenation (H/R). The ATF3 overexpression-H/R cell model by transfecting ATF3 plasmid into the H9C2 cell line. The transcription levels of ATF3 and EGR1 were determined using RT-qPCR, the levels of TNF-α and IL-6 were determined using ELISA kits, the protein expression of LC3 I, LC3 II, and P62 was determined via WB, and microstructure of H9C2 cell was observed by transmission electron microscopy (TEM). Overexpression of ATF3 significantly downregulated Egr1 levels, indicating that EGR1 might be the target of ATF3. By upregulating ATF3 levels, the extracellular levels of the inflammatory cytokines TNF-α and IL-6 significantly decreased, and the protein expression of the autophagy markers LC3 I, LC3 II, and P62 significantly increased. TEM results revealed that the cell line in the H/R-ATF3 group exhibited a higher abundance of autophagosome enclosures of mitochondria. The results indicated that ATF3/EGR1 may alleviate inflammation and improve autophagy in an H/R-induced MIRI model of cardiomyocytes.

Lactoferrin mediates epithelial-mesenchymal transformation by regulating the PI3K/AKT/mTOR pathway to inhibit nasopharyngeal carcinoma metastasis

2024-04-22T20:37:25+02:00

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. Epithelial-mesenchymal transition (EMT) is a major player in regulating NPC transfer. There is increasing evidence that lactotransferrin (LTF) is an important regulator of EMT conversion. However, the potential role and mechanisms of LTF in regulating NPC cell EMT remain unclear. In this study, quantitative real-time PCR (qRT‒PCR) and Western blotting were applied to measure the expression of LTF in NPC cells. Subsequently, the influences of LTF on the proliferation, migration and invasion of NPC cells were verified by functional acquisition experiments. Finally, Western blotting was used to analyze the effects of EMT-related proteins and phosphoinositol 3-kinase (PI3K)/Akt/mammalian rapamycin target (mTOR) signaling pathways. The data of this study indicate that LTF was underexpressed in human NPC cells, and upregulation of LTF could restrain NPC cell proliferation, invasion, migration and EMT transformation. Moreover, the effects of LTF on NPC cell metastasis and EMT are partly determined by the PI3K/AKT/mTOR pathway. This study suggests that LTF is a potential biomarker of NPC and that LTF-mediated EMT progression plays a tumor-suppressive role in the progression of NPC metastasis.

Identification of core genes of craniopharyngioma angiogenesis based on single-cell nuclear transcriptome sequencing

2024-04-22T20:37:12+02:00

This study aimed to explore the core genes of craniopharyngioma angiogenesis for targeted vascular therapy based on single-cell nuclear transcriptome sequencing. For single-cell nuclear transcriptome sequencing, we collected six samples from the tumor center and adjacent hypothalamic tumor tissues from three patients with craniopharyngioma, as well as four normal brain tissues based on Gene Expression Omnibus. We screened genes with differential up-regulation between vascular endothelial cells of craniopharyngioma and those of normal brain tissues, performed GO and KEGG analysis, constructed the protein-protein interaction network, and selected key genes verified using immunofluorescence. After data cleaning and quality control, 623 craniopharyngioma endothelial cells and 439 healthy brain endothelial cells were obtained. Compared with normal brain endothelial cells, craniopharyngioma endothelial cells were screened for 394 differentially up-expressed genes (DEGs). GO and KEGG results showed that DEGs probably modulated endothelial cells, adherens junction, focal adhesion, migration, actin cytoskeleton, and invasion via the PI3K-AKT, Rap1, Ras, Wnt, and Hippo pathways. The core genes screened were CTNNB1, PTK2, ITGB1, STAT3, FYN, HIF1A, VCL, SMAD3, PECAM1, FOS, and CDH5. This study obtained possible anti-angiogenic genes in craniopharyngioma. Our results shed novel insights into molecular mechanisms and craniopharyngioma treatment.

Knockdown of lncRNA AU020206 could inhibit microglia apoptosis in ischemic stroke

2024-04-22T20:37:19+02:00

The diagnostic biomarkers associated with ischemic stroke (IS) that may have clinical utility remain elucidated. Thus, the potential functional lncRNAs in IS were explored. The Gene Expression Omnibus database provided the transcriptome profile of IS for download. WGCNA analysis and integrated bioinformatics were used to find genes that were differentially expressed (DEGs). The Starbase database created the lncRNA-based ceRNA network. In order to investigate the molecular mechanism and involved pathways of DEGs in IS, functional enrichment analysis was carried out. Using qRT-PCR, lncRNAs identified as putative IS biomarkers were confirmed to be expressed in a permanent middle cerebral artery occlusion (MCAO) model. Using the annexin V/PI apoptosis test, the amount of apoptosis in oxygen-glucose deprivation (OGD) cells was measured. A total of 1600 common differentially expressed - protein-coding RNA (DE-pcRNAs) and 26 DE-lncRNAs were identified. The results of enrichment analysis indicate that the cytokine may be regulated by common DE-pcRNAs and are vital in the progress of IS. A lncRNAs-mediated ceRNA network including lncRNAs AU020206, Brip1os, F630028O10Rik and 9530082P21Rik was constructed. The expression of these lncRNAs was significantly increased in MCAO model. Knockdown of lncRNA AU020206 inhibited microglia apoptosis in OGD cell model. We constructed a lncRNAs-mediated ceRNA network and found that lncRNA AU020206 inhibited microglia apoptosis in OGD cell model. These findings provided further evidence for the diagnosis and a novel avenue for targeted therapy of IS.

Identification of DLEU2 as biomarker based on lncRNA-Mediated ceRNA network in rupture of intracranial aneurysm

2024-04-22T20:37:26+02:00

Intracranial aneurysms (IA) is a potentially devastating clinical problem that may cause lethal subarachnoid hemorrhage upon rupture, but the molecular mechanisms remain further elucidated. Our goal in this work was to build the lncRNA-mediated ceRNA network in IS and explore the associated pathways and functions. The deep transcriptome sequencing dataset profile of rupture of IA and normal tissues (SRP150595) was obtained from NCBI database. To determine which genes were differently expressed, weighted gene co-expression network analysis and other integrated bioinformatics techniques were used (DEGs). The action mechanism and associated pathways of DEGs in IA were investigated using GO annotations and KEGG analysis. The Starbase database was used to build the ceRNA network. Vascular smooth muscle cells (VSMC) were used for the transwell assay and CCK-8. A total of 248 common differentially expressed-protein coding RNA and 76 DE-lncRNAs were obtained. Functional enrichment analysis indicated that the DEGs of IA are involved in pathways of inflammation and immune response. A lncRNAs-mediated ceRNA network including lncRNAs BASP1-AS1, DLEU2, LINC02035, LINC02363, MMP25-AS1, AC008771.1 was constructed. The biological behavior of VSMC was suppressed when DLEU2 was knocked down. In conclusion, a lncRNAs-mediated ceRNA network was constructed in IA based on the integrated bioinformatics analyses, in which DLEU2 was identified to be a novel and potential biomarker of IA.

"Simmer pus and grow flesh" method promotes chronic wound healing in rats via bFGF-Wnt β-catenin signaling pathway

2024-04-22T20:37:14+02:00

The purpose of this study was to explore the mechanism of "simmer pus and grow meat" method based on bFGF regulating WNT / β-Catenin signaling pathway. Of 100 SPF rats, 25 were randomly selected as blank group, and 75 rats were established chronic infectious wound model and divided into blank group, model group (normal saline treatment, n = 25), experimental group (purple and white ointment treatment, n = 25), and wet burn ointment group (wet burn treatment, n = 25). The wound healing rate of rats was compared. The protein expressions of PCAN, VEGF, bFGF, β-Catenin, GSK-3β and C-Myc in granulation tissues were detected. On the 7th day, the wound healing rate of the model group was lower than that of the other 3 groups (P<0.05), and the wound healing rate of the positive control group was higher than that of the experimental group and the control group (P<0.05). The expressions of bFGF, GSK-3β and C-MyC in model group were higher than those in control group (P<0.05). The β-catenin protein expression in the model group was lower than that in the control group (P<0.05), and the β-catenin protein expression in the experimental group and the positive control group was higher than that in the model group (P<0.05). The expressions of PCAN and VEGF in model group were lower than those in model group (P<0.05). We found that Zibai ointment promotes chronic wound healing by modulating the bFGF/Wnt/β-Catenin signaling pathway.

Knockdown of growth differentiation factor-15 restrains prostate cancer through regulating MAPK/ERK signaling pathway

2024-04-22T20:37:22+02:00

Prostate cancer, prevalent among males, is influenced by various molecular factors, including Growth Differentiation Factor 15 (GDF15). Despite its recognized role in multiple tumor types, GDF15's specific involvement in prostate cancer remains insufficiently explored. This study investigates the regulatory function of GDF15 in prostate cancer. To explore GDF15's impact, we established GDF15 knockdown and overexpression models in prostate cancer cells. We quantified mRNA and protein levels using RT-PCR and Western blotting. Functional assays, including CCK8, Transwell, wound healing, and flow cytometry, were employed to evaluate cell proliferation, invasion, migration, and apoptosis. Additionally, the effect of GDF15 on tumor growth was assessed using a metastatic tumor model in nude mice. Elevated GDF15 expression was identified in prostate cancer tissues and cells. The knockdown of GDF15 led to the activation of the MAPK/ERK signaling pathway. C16PAF was found to counteract the inhibitory effects of sh-GDF15 on cell proliferation, invasion, migration, and apoptosis in LNCaP cells. It also reversed the sh-GDF15-induced alterations in the epithelial-mesenchymal transition (EMT) process. In vivo, C16PAF notably mitigated the sh-GDF15-induced suppression of tumor growth. The study demonstrated that sh-GDF15 inhibits cell proliferation, invasion, migration, EMT process, and tumor growth, while it promotes apoptosis. However, these effects were significantly reversed by C16PAF. The study underscores the potential of GDF15 as a target for novel therapeutic interventions in prostate cancer treatment and prevention. These findings illuminate GDF15's multifaceted role in prostate cancer pathogenesis and suggest its viability as a therapeutic target.

The influence of genetic predisposition to oxidative stress on painful diabetic peripheral neuropathy: A mendelian randomization study

2024-04-22T20:37:29+02:00

Genetic predisposition to oxidative stress (OS) may influence the risk of Painful Diabetic Peripheral Neuropathy (PDPN). This study employed a Mendelian Randomization (MR) approach to investigate the causal relationship between genetic predisposition to OS and PDPN. Genetic instruments associated with OS biomarkers were selected as exposures. Summary-level data on PDPN was obtained from the largest available genome-wide association study (GWAS). MR analyses were conducted using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the MR-Egger, weighted median, and MR-PRESSO approaches. Genetic predisposition to increased glutathione S-transferase (GST) activity was associated with a reduced risk of PDPN (OR=0.66, 95%CI: 0.49-0.89, P=0.006). Higher ascorbate levels conferred a protective effect against PDPN (OR=0.83, 95%CI: 0.71-0.97, P=0.018). No significant association was observed between genetic predisposition to OS biomarkers and PDPN severity. Genetic predisposition to increased GST activity and higher ascorbate levels protect against the development of PDPN, suggesting a causal relationship.

Chelerythrine induces apoptosis and ferroptosis through Nrf2 in ovarian cancer cells

2024-04-22T20:37:17+02:00

Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.

Small nucleolar RNA host gene 1 silence inhibits the lipopolysaccharide-induced microglial apoptosis and inflammation

2024-04-22T20:37:10+02:00

Microglia activation is an early mediator of neuroinflammation and a major contributor to spinal damage and motor dysfunction. This study was designed to investigate the role of small nucleolar RNA host gene 1 (SNHG1) on the apoptosis and inflammatory response of microglial cell BV-2 and its underlying molecular mechanism. The C5 lamina contusion-induced mouse model of spinal cord injury (SCI) was constructed. Mouse microglia BV2 was stimulated by lipopolysaccharide (LPS) to establish the in vitro model of SCI. The quantitative reverse transcription polymerase chain reaction method was used to quantify RNA expression levels. Enzyme-linked immunosorbent assays were used to quantify concentrations of inflammatory cytokines. Protein levels were assessed by western blotting, and apoptosis was assessed by flow cytometry. Dual luciferase reporter gene assay and RNA pull-down assay were conducted to investigate the binding relationships between molecules. Upregulation of SNHG1 and downregulation of miR-195-5p were observed in the spinal cords of SCI mouse model. LPS treatment led to elevation of SNHG1 expression in BV2 cells, as well as accelerated apoptosis and inflammation. Evident mitigation of LPS-induced BV2 cell damage was observed after SNHG1 knockdown. MiR-195-5p was identified as a target of SNHG1. Inhibition of miR-195-5p restored the impact of SNHG1 knockdown on cell damage of LPS-treated BV2 cells. Furthermore, miR-195-5p can target activating transcription factor-6 (ATF6). In summary, SNHG1 knockdown ameliorates LPS-induced microglial apoptosis and inflammatory response via the miR-195-5p/ATF6 axis, providing a novel direction for SCI treatment.

Diagnostic value of high-frequency ultrasound combined with fine needle aspiration cytology and BRAF gene for papillary thyroid microcarcinoma

2024-04-22T20:37:08+02:00

We attempted to evaluate clinical application value of high-frequency ultrasound (HFUS), fine needle aspiration cytology (FNAC), BRAF gene, and combination of HFUS, FNAC, and BRAF gene in diagnosing papillary thyroid microcarcinoma (PTMC). The 150 patients with thyroid minimal lesions who underwent HFUS, FNAC and BRAF gene testing before surgery in our hospital from June 2020 to December 2021 were selected as research subjects. Patients were divided into two groups based on postoperative pathological results. The consistency of diagnostic results of HFUS, FNAC, and BRAF gene and their combination with those of pathological examination, diagnostic efficacy of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis, and diagnostic value of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis received analysis and comparison. The consistency of diagnostic results of combined detection with pathological examination exhibited elevation relative to that of HFUS, FNAC and BRAF gene detection alone (P < 0.05). The negative predictive value, sensitivity and accuracy of combined detection exhibited elevation relative to individual detection (P < 0.05). The AUC of combined detection in diagnosing PTMC lymph node metastasis exhibited elevation relative to that of HFUS and BRAF gene alone (P < 0.05). HFUS combined with FNAC and BRAF genes possesses high diagnostic value, with high diagnostic sensitivity, specificity, and accuracy. Thus, combined detection for PTMC before surgery can accurately determine whether lymph node metastasis occurs, reduce occurrence of missed diagnosis and misdiagnosis, and thus improve diagnostic precision.

Identification of important genes for human periodontal ligament cells in response to mechanical force based on WGCNA

2024-04-22T20:37:07+02:00

To identify the differentially important genes of human periodontal ligament cells (PDLC) in response to different types of force, the dataset with regard to human PDLC in response to force was retrieved from the GEO. Differentially expressed genes (DEG) analysis between mechanical force (MF) and the control group was conducted. The gene set enrichment analysis (GSEA) was applied to identify the functional enrichment in different MF groups. Weighted gene co-expression network analysis (WGCNA) of transcriptomic data was performed to identify the highly correlated genes in human PDLC in response to MF. The Lasso regression model was applied to screen the key genes. Results showed A total of 2861 DEGs were identified between the MF group and control group, including 1470 up-regulated DEGs and 1391 down-regulated DEGs. Different biological processes were enriched between the static group and the intermittent group. The Myc targets, TGF-β signaling pathway and PI3K/AKT/MTOR signaling pathway were enriched in intermittent-MF and static-MF groups. The turquoise module (including 386 hub genes) in WGCNA was highly correlated with intermittent traits and the black module (including 33 hub genes) was positively correlated with static traits. The lasso analysis result showed that the CLIC4, NPLOC4 and PRDX6 had the greatest impact on the human PDLC with mechanic stimuli with good predictive efficiency. In conclusion, we developed important genes for human PDLC in response to MF, which might be potential markers for orthodontic tooth movement.

DNMT1 methylation of LncRNA-ANRIL causes myocardial fibrosis pyroptosis by interfering with the NLRP3/Caspase-1 pathway

2024-04-22T20:37:05+02:00

Myocardial fibrosis is a common pathological manifestation that occurs in various cardiac diseases. The present investigation aims to reveal how DNMT1/lncRNA-ANRIL/NLRP3 influences fibrosis and cardiac fibroblast pyroptosis. Here, we used ISO to induce myocardial fibrosis in mice, and LPS and ATP to induce myocardial fibroblast pyroptosis. The results showed that DNMT1, Caspase-1, and NLRP3 expression were significantly increased in fibrotic murine myocardium and pyroptotic cardiac fibroblasts, whereas LncRNA-ANRIL expression was decreased. DNMT1 overexpression decreased the level of LncRNA-ANRIL while increasing the levels of NLRP3 and Caspase-1. Contrarily, silencing DNMT1 increased the LncRNA-ANRIL and decreased the levels of NLRP3 and Caspase-1. Silencing LncRNA-ANRIL increased the levels of NLRP3 and Caspase-1. The present findings suggest that DNMT1 can methylate LncRNA-ANRIL during the development of myocardial fibrosis and CFs cell scorching, resulting in low LncRNA-ANRIL expression, thereby influencing myocardial fibrosis and cardiac fibroblast pyroptosis.

circ_JMJD1C expedites breast cancer progression by regulating miR-182-5p/JMJD1C/SOX4 axis

2024-04-22T20:37:02+02:00

Circular RNAs (circRNAs) are engaged in various types of cancers. This study aimed to investigate the roles of circ_0006743 (circ_JMJD1C) in breast cancer. The downstream of circ_JMJD1C and their interaction network was determined by bioinformatic analyses. Gene expression were analyzed through western blot and qRT-PCR assays. Functional assays were conducted in vitro and in vivo to verify circ_JMJD1C role in BC. FISH and confocal analysis indicated the cellular distribution of circ_JMJD1C. Luciferase reporter, RNA immune-precipitation (RIP) assays, as well as Pearson’s correlation analysis, were implemented to test the relation of miR‐182-5p, JMJD1C and circ_JMJD1C. Circ_JMJD1C and JMJD1C expression were both elevated, and their expression was positively correlated in BC. Circ_ JMJD1C knockdown hindered BC cell proliferation, invasion, and migration, along with epithelial-mesenchymal transition (EMT) in vitro and in vivo. Circ_JMJD1C facilitated BC progression by the miR‐182-5p-JMJD1C axis. Circ_JMJD1C epigenetically upregulated SOX4. Circ_JMJD1C promotes the aggressiveness of BC via regulating miR‐182-5p/JMJD1C/SOX4 axis. This may provide a novel and promising therapy targeting BC.

Research of the unrecognised functions of miR-375 in prostate cancer cells

2024-04-22T20:37:01+02:00

Many cancers, including prostate cancer, have miRNAs with altered expression levels. These miRNAs play a pivotal role in regulating cancer initiation, invasion, and metastasis. miRNAs are an important component in cancer diagnosis and therapy and can play a key role as biomarkers or chemotherapeutic agents. This investigation aimed to show the effects of miR-375 on PCa. In this project, target prediction tools and the KEGG pathway were performed to determine the potential targets of miR-375. Transfection was performed using miR-375 mimic and inhibitor. The actions of miRNAs on cell viability and migration were examined in PCa cells. In addition, qRT-PCR was executed to evaluate changes in gene expression in the PI3K-mTOR pathway. The analyses exposed that the upregulation of miR-375 repressed the viability at 48 h. While stimulation of miR-375 did not repress the migration, suppression of miR-375 reduced the migration at 24 and 48 hours. The predicted target TSC1 gene is not directly targeted by miR-375. Interestingly, in response to PIK3CA increase, mTOR expression was suppressed in all cells except LNCAP cells. In conclusion, miR-375 has anti-proliferative and cell migration inhibitory effects in prostate cancer. However, studies demonstrate that miR-375 may have tumor suppressor and oncogenic effects when considering cell molecular differences.

Molecular mechanism of high glucose-induced mitochondrial DNA damage in retinal ganglion cells

2024-04-22T20:36:59+02:00

Mitochondrial DNA damage in retinal ganglion cells (RGCs) may be closely related to lesions of glaucoma. RGCs were cultured with different concentrations of glucose and grouped into 3 groups, namely normal control (NC) group, Low-Glu group, and High-Glu group. Cell viability was measured with cell counting kit-8, and cell apoptosis was measured using flow cytometry. The DNA damage was measured with comet assay, and the morphological changes of damaged mitochondria in RGCs were observed using TEM. Western blot analyzed the expression of MRE11, RAD50, and NBS1 protein. Cell viability of RGCs in Low-Glu and High-Glu groups were lower than that of NC group in 48 and 96 h. The cell apoptosis in NC group was 4.9%, the Low-Glu group was 12.2% and High-Glu group was 24.4%. The comet imaging showed that NC cells did not have tailings, but the low-Glu and high-Glu group cells had tailings, indicating that the DNA of RGCs had been damaged. TEM, mitochondrial membrane potential, ROS, mitochondrial oxygen consumption, and ATP content detection results showed that RGCs cultured with high glucose occurred mitochondrial morphology changes and dysfunction. MRE11, RAD50, and NBS1 protein expression associated with DNA damage repair pathway in High-Glu group declined compared with Low-Glu group. Mitochondrial DNA damage caused by high glucose will result in apoptosis of retinal ganglion cells in glaucoma.

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation

2024-04-22T20:36:57+02:00

Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.

The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation

2024-04-22T20:36:56+02:00

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma

2024-04-22T20:36:54+02:00

Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Importin7 (IPO7) is responsible for nucleoplasmic transport of RNAs and proteins, and it has been confirmed to be involved in the development of human cancers. This study aimed to explore the function and mechanism of IPO7 in OSCC. IPO7 expression in tissues and cells was determined by RT-qPCR. Cell proliferative, migratory, and invasive capabilities were detected through transwell assay and colony formation assay. Mice xenograft models were established for evaluating tumor growth. Autophagy was estimated by the LC3 levels in cells through western blot and immunofluorescence (IF). Western blot was utilized to detect the key proteins in PERK/EIF2AK3/ATF4 pathway for assessing the endoplasmic reticulum stress (ERS). The interaction of IPO7 and homeobox A10 (HOXA10) was tested by GST pull-down assay and Co-IP assay. ChIP assay and luciferase reporter assay were utilized to determine the combination of HOXA10 and EIF2AK3. We proved that IPO7 was upregulated in OSCC tissues and cells, and its depletion reduced cell proliferation, migration, invasion and tumor growth. Furthermore, LC3 expression in cells was found to be reduced by IPO7 knockdown. IPO7 promoted OSCC tumor metastasis by activating autophagy. Additionally, we discovered that IPO7 could regulate ERS by activating the PERK/ATF4 pathway. EIF2AK3 upregulation can promote cell autophagy. Furthermore, IPO7 was proven to promote nuclear translocation of HOXA10 in cells. EIF2AK3 promoter can bind to HOXA10. Rescue assay confirmed that HOXA10 upregulation can reverse the effect of IPO7 silencing on OSCC progression. IPO7 can enhance proliferation, migration, invasion, and autophagy by nuclear translocation of HOXA10 and the activation of EIF2AK3/ATF4 pathway in OSCC.

MiR-34a ameliorates arterial blood flow in rats with lower limb arteriosclerosis obliterans via Sirt1 signaling pathway

2024-04-22T20:36:52+02:00

In this study, we investigated the impact of microRNA-34a (miR-34a) on lower limb arteriosclerosis obliterans in rats through the Sirtuin 1 (Sirt1) signaling pathway. Thirty-six Sprague-Dawley rats were divided into normal, model, and miR-34a mimics groups. Rats in the normal group were raised normally, while the model group underwent lower limb arteriosclerosis obliterans induction and received saline injections. The miR-34a mimics group also underwent arteriosclerosis obliterans modeling but received miR-34a mimics injections. Immunohistochemistry revealed significantly increased vascular endothelial growth factor (VEGF) expression in both model and miR-34a mimics groups compared to the normal group, with the miR-34a mimics group showing higher levels. Western blotting indicated elevated Sirt1 protein expression in both non-normal groups, with the miR-34a mimics group exhibiting significantly higher levels. Quantitative polymerase chain reaction (qPCR) demonstrated higher levels of miR-34a, VEGF mRNA, and Sirt1 mRNA in the model group compared to the normal group, but significantly lower levels than the miR-34a mimics group. Enzyme-linked immunosorbent assay (ELISA) showed increased VEGF content in the model group compared to the normal group but decreased compared to the miR-34a mimics group. Hemorrheological detection revealed a reduced PU index in both non-normal groups compared to the normal group, with a significant increase in the miR-34a mimics group compared to the model group. Overall, miR-34a upregulation enhanced VEGF expression in rat blood vessels, ameliorating arterial blood flow in lower limb arteriosclerosis obliterans through the Sirt1 signaling pathway.

Clinical value of KiSS-1 and MMP-2 expression levels in breast cancer tissue in evaluating prognosis of elderly breast cancer patients after modified radical mastectomy

2024-04-22T20:37:49+02:00

We attempted to clarify clinical value of KiSS-1 and MMP-2 levels in breast cancer (BC) tissue in evaluating
prognosis of elderly BC patients after modified radical mastectomy (MCM). The data of 192 elderly female
BC patients receiving MCM in our hospital from January 2018 to December 2022 were collected. According
to prognosis, patients received division into poor prognosis group (n = 43) and good prognosis group (n =
149). The serum CEA level and KiSS-1 and MMP-2 levels in BC tissue received measurement in both groups.
The predictive value of KiSS-1 and MMP-2 alone and jointly in adverse prognosis of elderly BC patients after
MCM received assessment. Results showed that No statistical significance was exhibited between both groups
in general data (P > 0.05). The serum CEA level and MMP-2 expression in BC tissue in poor prognosis group
exhibited elevation relative to those in good prognosis group, and KiSS-1 expression in BC tissue in poor
prognosis group exhibited depletion relative to that in good prognosis group, indicating statistical significance
(P < 0.05). The high-level KiSS-1 might be a protective element for adverse prognosis of elderly BC patients
after MCM, and high-level CEA and MMP-2 might be an independent risk element for adverse prognosis of
elderly BC patients after MCM (P < 0.05). KiSS-1 and MMP-2 alone and jointly predicted AUC of adverse
prognosis in elderly BC patients after MCM were 0.93, 0.802 and 0.958, with certain predictive values; when
cutoff values of KiSS-1 and MMP-2 were 6.15 and 2.26, the predictive value was the best. In conclusion,
KiSS-1 and MMP-2 levels in BC tissue possess relation to adverse prognosis of MCM. KiSS-1 and MMP-2
levels in elderly BC patients before surgery may be detected in the future to assist in prognosis evaluation of
elderly BC patients after MCM.