BioMed Research International
ISSN / EISSN : 2314-6133 / 2314-6141
Current Publisher: Hindawi Limited (10.1155)
Total articles ≅ 19,329
Latest articles in this journal
BioMed Research International, Volume 2020, pp 1-33; doi:10.1155/2020/8838524
Ischemia-reperfusion injury (IRI) elicits tissue injury involved in a wide range of pathologies. Multiple studies have demonstrated that noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), participate in the pathological development of IRI, and they may act as biomarkers, therapeutic targets, or prognostic indicators. Nonetheless, the specific molecular mechanisms of ncRNAs in IRI have not been completely elucidated. Regulatory networks among lncRNAs/circRNAs, miRNAs, and mRNAs have been the focus of attention in recent years. Studies on the underlying molecular mechanisms have contributed to the discovery of therapeutic targets or strategies in IRI. In this review, we comprehensively summarize the current research on the lncRNA/circRNA-miRNA-mRNA axes and highlight the important role of these axes in IRI.
BioMed Research International, Volume 2020, pp 1-9; doi:10.1155/2020/1621394
The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.
BioMed Research International, Volume 2020, pp 1-10; doi:10.1155/2020/2329196
Purpose. Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumors in the world. Genetic variants have an important role in HNSCC progression. Our study is aimed at exploring the relationship between MIR17HG polymorphisms and HNSCC risk in the Chinese Han population. Methods. We recruited 537 HNSCC cases and 533 healthy subjects to detect the correlation of six polymorphisms in MIR17HG with HNSCC susceptibility. The associations were evaluated by computing odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analysis. Results. Our study revealed that rs7336610 (OR 1.77, 95 % CI = 1.09 ‐ 2.86 , and p = 0.021 ) and rs1428 (OR 1.73, 95 % CI = 1.07 ‐ 2.81 , and p = 0.025 ) are strongly associated with increased susceptibility to HNSCC in men. Besides, rs17735387 played a crucial protective role in stage III/IV HNSCC patients (OR 0.34, 95 % CI = 0.12 ‐ 0.95 , and p = 0.040 ) compared with stage I/II. Conclusion. Our study firstly indicated that MIR17HG polymorphisms are significantly associated with HNSCC susceptibility, which suggests that MIR17HG has a potential role in the occurrence of HNSCC.
BioMed Research International, Volume 2020, pp 1-20; doi:10.1155/2020/8838676
Obesity is directly associated with the risk of cancer in different organs, including breast, colon, and kidney. However, adipocytes could be utilized to control progression for some types of cancer, such as leukemia and breast cancer. To explore the potential correlation between adipocytes and cancer, the combined effect of expression levels of obesity-related genes and clinical factors (i.e., gender, race, menopausal status, history of smoking, tumor grade, body mass index (BMI), and history of drinking) on cancer survival rate was systemically studied. The expression levels of obesity-related genes in cancer tissues and normal tissues were downloaded from The Cancer Genome Atlas (TCGA). Kaplan–Meier curves were plotted using R programming language. The log-rank test was applied to explore the correlation between different clinical subgroups. The overexpression of the nine obesity-related genes (MC4R, TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, FTO, PCSK1, and GPR120) may associate with tumor-promoting factors in some organs (head and neck, gastrointestinal tract, liver, and gallbladder). Underexpressed LEPR, NEGR1, TMEM18, and SH2B1 genes prevented the progression and metastasis of kidney cancer. The combined effect of clinical factors and the expression levels of obesity-related genes on patients’ survival was found to be significant. Our outcomes suggested that the alternations of DNA methylation patterns could result in the changes of expression levels of obesity-related genes, playing a critical role in tumor progression. The results of the current study may be utilized to supplement precision and personalized medicine, as well as provide novel insights for the development of treatment approaches for cancer.
BioMed Research International, Volume 2020, pp 1-7; doi:10.1155/2020/6808409
Objective. To elucidate the characteristics of symptomatic attack of rudimentary uteri in MRKH syndrome and highlight the rare and unexpected possibilities. Methods. A cohort of 202 Chinese MRKH syndrome patients admitted to the Peking Union Medical College Hospital from Jan 2009 to Dec 2016 was analyzed retrospectively. Based on the symptoms of abdominal pain before vaginoplasty, the patients were categorized into the asymptomatic and symptomatic groups. Results. Totally, 21 patients had their uteri removed due to obstructive bleeding, 19 of them had symptoms of abdominal pain before vaginoplasty, the mean duration of abdominal pain before artificial vaginoplasty was 5.0 years (range, 0.5–10 years), and the mean age at first onset of recurrent abdominal pain was 14.3 years old (range 11–18). Two special cases showed unusual long incubation periods up to 23 years. Ultrasound detected endometrioid echo in four asymptomatic patients. Among the symptomatic group, 7 patients had no imaging evidence for endometrial cavities despite clinical pain. Two of them developed severe symptoms over the next two or four years and eventually had their uteri removed. Two patients reported persistent abdominal pain with a visual analog scale (VAS) score of 4–5, still under observation. Three patients were lost to follow-up. Conclusion. More than 10% of the patients with MRKH syndrome had surgical indication to remove the rudimentary uteri. The discrepancy between clinical symptoms and imaging calls for the vigilance for prophylactic surgery or prolonged follow-up.
BioMed Research International, Volume 2020, pp 1-15; doi:10.1155/2020/8024138
Lung adenocarcinoma (LUAD) is a major pathological type of lung cancer. Understanding the mechanism of LUAD at the molecular level is important for a clinical decision. In this study, we use bioinformatic analysis to explore the prognostic value of P4HA1 in lung adenocarcinoma (LUAD) and the relationship with prognosis and tumor-infiltrating immune cells (TIICs). The results showed that the expression of P4HA1 was significantly higher in tumor tissues than in normal tissues for LUAD patients. Upregulated P4HA1 was related to stage and T classification. Kaplan-Meier analysis indicated that upregulation of P4HA1 was significantly related to worse overall survival (OS). Univariate and multivariate Cox analysis indicated P4HA1 remained to be an independent prognostic factor. GSEA showed that several cancer-related and immune-related signaling pathways exhibited prominently differential enrichment in P4HA1-high expression phenotype. In addition, the expression of P4HA1 was significantly correlated with proportion of several TIICs, particularly B cells and CD4+ T cells. In conclusion, our study confirmed that P4HA1 is a promising biomarker of poor prognosis and relates to immune infiltrates in LUAD.
BioMed Research International, Volume 2020, pp 1-16; doi:10.1155/2020/4029062
Background. Triple-negative breast cancer (TNBC) is usually poorly differentiated, highly invasive, susceptible to distant metastasis, and less responsive to endocrine and targeted therapy. However, immunotherapy is a promising treatment for TNBC patients recently. Methods. The prognostic value of immune-related genes (IRGs) was explored by using RNA sequencing and microarray data of 123 and 107 TNBC patients from TCGA and GEO databases, respectively. Results. In TCGA database, GO and KEGG pathway analysis of 119 differential IRGs indicated that they actively participate in the interaction of cytokines and receptors. A nomogram model constructed by the prognosis-related CCL25, IL29, TDGF3, GPR44, and GREM2 in the IRGs could personalize and visualize the 1-, 2-, 3-, 4-, and 5-year overall survival (OS) of TNBC patients. Moreover, TNBC patients could be defined as low-risk ( risk score < 194 ) or high-risk ( risk score ≥ 194 ) cohorts based on the risk score derived from the nomogram model. The results could be validated by the GSE58812 dataset. Furthermore, the risk score was an independent risk factor for TNBC patients ( HR = 1.019 , 95% CI 1.012-1.027, p < 0.001 ) and was positively related to stage ( p = 0.017 ). Interestingly, the risk score could reflect the infiltration of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, and neutrophils. Conclusion. These findings provided a reference for personalized OS prediction in TNBC patients and might be potential immune biomarkers for designing novel therapy.
BioMed Research International, Volume 2020, pp 1-30; doi:10.1155/2020/9593254
Hepatocellular carcinoma is the fifth most common cancer worldwide and the second most lethal, following lung cancer. Currently applied therapeutic practices rely on surgical resection, chemotherapy and radiotherapy, or a combination thereof. These treatment options are associated with extreme adversities, and risk/benefit ratios do not always work in patients’ favor. Anomalies of the epigenome lie at the epicenter of aberrant molecular mechanisms by which the disease develops and progresses. Modulation of these anomalous events poses a promising prospect for alternative treatment options, with an abundance of felicitous results reported in recent years. Herein, the most recent epigenetic modulators in hepatocellular carcinoma are recapitulated on.
BioMed Research International, Volume 2020, pp 1-6; doi:10.1155/2020/8810747
Purpose. This study is aimed at investigating bone regeneration in critical-sized defects in rabbit calvarium using a novel nano- (n-) hydroxyapatite hybrid scaffold with concentrated growth factors (CGFs). Methods. Twenty-four male adult rabbits were chosen to establish a critical-sized bone defect model and randomly divided into two groups. Two defects of 15 mm diameter each were created in the parietal bone of each animal. Group A had n-hydroxyapatite hybrid scaffold placed in the experimental defect on the right, and the left defect was unfilled as blank. Group B had hydroxyapatite hybrid scaffold mixed with CGF placed in the right defect and CGF on the left. Six animals in each group were sacrificed after 6 and 12 weeks. Cone-beam computed tomography system scanning and hematoxylin and eosin (HE) staining were used to detect osteogenesis within the defects. Results. The treatment with n-hydroxyapatite hybrid scaffold along with CGF resulted in a significantly higher amount of new bone at 6 and 12 weeks compared to the treatment with CGF alone and the controls. No apparent inflammation and foreign body reaction were observed through HE staining. Conclusions. The new synthesized n-hydroxyapatite hybrid scaffold and CGF can be applied for bone defect regeneration to promote the process to a certain extent.
BioMed Research International, Volume 2020, pp 1-10; doi:10.1155/2020/6143542
We investigated the role of Akt1, one of the three isoforms of Akt, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO). We subjected wild type and Akt1−/− mice to UUO. The Akt1 gene was silenced in vitro using short hairpin RNA delivered via a lentiviral vector in human proximal tubular cells (HK2 cells) and kidney fibroblasts (NRK-49F cells). The obstructive kidneys of Akt1−/− mice showed more severe tubulointerstitial fibrosis than those of wild type mice. The expression of fibronectin and type I collagen was significantly increased in obstructed kidneys of Akt1−/− mice compared to those of wild type mice. The important finding was that the expression of transforming growth factor β1 (TGFβ1) was significantly increased in the Akt1−/− mice compared to the wild type mice. The knockdown of Akt1 enhanced the expression of TGFβ1 in HK2 cells. Interestingly, the upregulation of TGFβ1 due to genetic knockdown of Akt1 was associated with activation of signal transducer and activator of transcript 3 (STAT3) independently of the Smad pathway in NRK-49F and HK2 cells. Immunohistochemical staining also showed that expression of phosphorylated STAT3 was more increased in Akt1−/− mice than in wild type mice after UUO. Additionally, the deletion of Akt1 led to apoptosis of the renal tubular cells in both in vivo and in vitro studies. Conclusively, these results suggest that the deletion of Akt1 may contribute to renal fibrosis via induction of the TGFβ1/STAT3 pathway in a murine model of UUO.