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Project description:In orthodontic therapy periodontal tissue responds to mechanical stimuli by bone remodeling mediated by specific molecules involved in periodontal regeneration and homeostasis. The resulting changes are reflected in the salivary proteome that is emerging as a valuable diagnostic tool. We analyzed the changes of saliva proteome during orthodontic tooth movement in 12 healthy male patients, presented with malocclusion treated by placement of fixed orthodontic appliance. Six patients with identical dental pathology, but no orthodontic therapy were used as control samples. Saliva was collected a day before, immediately after, and 2, 7 and 30 days after the placement of the fixed orthodontic appliance and analyzed by LC-MS. Total of 198 proteins were identified and classified on the basis of their functional characteristics. Proteins involved in bone remodeling, inflammation and healing were detected mostly 30 days after placement of the fixed orthodontic appliance. At this time point, Bone morphogenetic protein 4 emerged as a central player in the ongoing dental bone remodeling. Besides BMP4, BMP antagonists: BMP Binding Endothelial Regulator (BMPER), Insulin-like growth factor-binding protein 3 (IGFBP3), Cytoskeleton-associated protein 4 (CKAP4) and Fibroblast growth factor 5 (FGF5), were also identified. Presence of BMP4 in human saliva 30 days after the placement of orthodontic fixed appliance was confirmed by ELISA and concentration of BMP4 was 3.2 pg/ml. To date, there is no published data on the presence of BMP molecules or their antagonists in saliva or the gingival cervical fluid, regardless of different orthodontic treatments or disease. BMP4 is involved not only in orthodontic treatment, but also in processes involving tooth development and homeostasis. Therefore, a better understanding of its networks in bone remodeling during OTM is heralded.
2021-09-09 | PXD016481 | Pride
Project description:The aim of our study was to evaluate the role of morphogenetic variability in functional outcome of patients with ischemic stroke. The prospective study included 140 patients with acute ischemic stroke, all of whom were tested upon: admission; discharge; one month post-discharge; and three months post-discharge. The age was analyzed, as well. The Functional Independence Measure (FIM) test and the Barthel Index (BI) were used for the evaluation of functional outcomes for the eligible participants. We analyzed the presence of 19 homozygous recessive characteristics (HRC) in the studied individuals. There was a significant change in FIM values at discharge (p = 0.033) and in BI values upon admission (p = 0.012) with regards to the presence of different HRCs. Age significantly negatively correlated for the FIM score and BI values at discharge for the group with 5 HRCs (p < 0.05), while for BI only, negative significant correlation was noticed for the group with 5 HRCs at three months post-discharge (p < 0.05), and for the group with 3 HRCs at one month post-discharge (p < 0.05) and three months post-discharge (p < 0.05). Morphogenetic variability might be one among potentially numerous factors that could have an impact on the response to defined treatment protocols for neurologically-impaired individuals who suffered an ischemic stroke.
| S-EPMC6627147 | biostudies-literature
Project description:RationaleBMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors, and downstream effectors have been reported in heritable PAH.ObjectivesTo determine how an acquired deficiency of BMP9 signaling might contribute to PAH.MethodsPlasma levels of BMP9 and antagonist soluble endoglin were measured in group 1 PAH, group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH.Measurements and main resultsBMP9 levels were markedly lower in portopulmonary hypertension (PoPH) versus healthy control subjects, or other etiologies of PAH or PH; distinguished PoPH from patients with liver disease without PAH; and were an independent predictor of transplant-free survival. BMP9 levels were decreased in mice with PH associated with CCl4-induced portal hypertension and liver cirrhosis, but were normal in other rodent models of PH. Administration of ALK1-Fc, a BMP9 ligand trap consisting of the activin receptor-like kinase-1 extracellular domain, exacerbated PH and pulmonary vascular remodeling in mice treated with hypoxia versus hypoxia alone.ConclusionsBMP9 is a sensitive and specific biomarker of PoPH, predicting transplant-free survival and the presence of PAH in liver disease. In rodent models, acquired deficiency of BMP9 signaling can predispose to or exacerbate PH, providing a possible mechanistic link between PoPH and heritable PAH. These findings describe a novel experimental model of severe PH that provides insight into the synergy between pulmonary vascular injury and diminished BMP9 signaling in the pathogenesis of PAH.
| S-EPMC6444661 | biostudies-literature
Project description:Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.
| S-EPMC8119687 | biostudies-literature
Project description:Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.
| S-EPMC8570002 | biostudies-literature
Project description:To screen the circulating miRNAs which can be used to evaluate the diagnosis and prognosis of sepsis by gene microarray,and to predict its target gene and mechanism by bioinformatics analysis in sepsis. To screen the circulating miRNAs which can be used to evaluate the diagnosis and prognosis of sepsis by gene microarray,and to predict its target gene and mechanism by bioinformatics analysis in sepsis.
2020-07-19 | GSE101639 | GEO
Project description:The incidence of human papillomavirus (HPV)-related head and neck cancer (HNSCC) is rising globally, presenting challenges for optimized clinical management. To date, it remains unclear which biomarker best reflects HPV-driven carcinogenesis, a process that is associated with better therapeutic response and outcome compared to tobacco/alcohol-induced cancers. Six potential HPV surrogate biomarkers were analyzed using FFPE tissue samples from 153 HNSCC patients (n = 78 oropharyngeal cancer (OPSCC), n = 35 laryngeal cancer, n = 23 hypopharyngeal cancer, n = 17 oral cavity cancer): p16, CyclinD1, pRb, dual immunohistochemical staining of p16 and Ki67, HPV-DNA-PCR, and HPV-DNA-in situ hybridization (ISH). Biomarkers were analyzed for correlation with one another, tumor subsite, and patient survival. P16-IHC alone showed the best performance for discriminating between good (high expression) vs poor outcome (low expression; p = 0.0030) in OPSCC patients. Additionally, HPV-DNA-ISH (p = 0.0039), HPV-DNA-PCR (p = 0.0113), and p16-Ki67 dual stain (p = 0.0047) were significantly associated with prognosis in uni- and multivariable analysis for oropharyngeal cancer. In the non-OPSCC group, however, none of the aforementioned surrogate markers was prognostic. Taken together, P16-IHC as a single biomarker displays the best diagnostic accuracy for prognosis stratification in OPSCC patients with a direct detection of HPV-DNA by PCR or ISH as well as p16-Ki67 dual stain as potential alternatives.
| S-EPMC8469433 | biostudies-literature
Project description:Background Bone morphogenetic proteins (BMPs) regulate tumor progression via binding to their receptors (BMPRs). However, the expression and clinical significance of BMPs/BMPRs in lung adenocarcinoma remain unclear due to a lack of systematic studies. Methods This study screened differentially expressed BMPs/BMPRs (deBMPs/BMPRs) in a training dataset combining TCGA-LUAD and GTEx-LUNG and verified them in four GEO datasets. Their prognostic value was evaluated via univariate and multivariate Cox regression analyses. LASSO was performed to construct an initial risk model. Subsequently, after weighted gene co-expression network analysis (WGCNA), differential expression analysis, and univariate Cox regression analysis, hub genes co-expressed with differentially expressed BMPs/BMPRs were filtered out to improve the risk model and explore potential mechanisms. The improved risk model was re-established via LASSO combining hub genes with differentially expressed BMPs/BMPRs as the core. In the testing cohort including 93 lung adenocarcinoma patients, immunohistochemistry (IHC) was performed to verify BMP5 protein expression and its association with prognosis. Results BMP2, BMP5, BMP6, GDF10, and ACVRL1 were verified as downregulated in lung adenocarcinoma. Survival analysis identified BMP5 as an independent protective prognostic factor. We also found that BMP5 was significantly correlated with EGFR expression and mutations, suggesting that BMP5 may play a role in targeted therapy. The initial risk model containing only BMP5 showed a significant correlation (HR: 1.71, 95% CI: 1.28−2.28, p: 3e-04) but low prognostic accuracy (AUC of 1-year survival: 0.6, 3-year survival: 0.6, 5-year survival: 0.63). Seventy-nine hub genes co-expressed with BMP5 were identified, and their functions were enriched in cell migration and tumor metastasis. The re-established risk model showed greater prognostic correlation (HR: 2.58, 95% CI: 1.92–3.46, p: 0) and value (AUC of 1-year survival: 0.72, 3-year survival: 0.69, and 5-year survival: 0.68). IHC results revealed that BMP5 protein was also downregulated in lung adenocarcinoma and higher expression was markedly associated with better prognosis (HR: 0.44, 95% CI: 0.23–0.85, p: 0.0145). Conclusion BMP5 is a potential crucial target for lung adenocarcinoma treatment based on significant differential expression and superior prognostic value.
| S-EPMC8569625 | biostudies-literature
Project description:Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities caused by an altered systemic host response to infection, has become the main cause of death among patients admitted to the intensive care units. Recently, genome-wide expression analysis revealed that over 80% of the essential genetic elements were altered in critically ill patients. Notably, non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs, have been proven to play essential roles in innate immunity, mitochondrial dysfunction and organ dysfunction. In this review, we introduced the biogenesis of non-coding RNAs briefly and summed up different kinds of non-coding RNAs in regulation of sepsis, which could provide a more comprehensive understanding about pathogenesis of the disease. Additionally, we summarized the limitations of current biomarkers and then recommended some non-coding RNAs as novel potential biomarkers for sepsis and sepsis-induced organ dysfunction. Besides, we also introduced some problems and challenges that need to be overcome during the clinical application of non-coding RNAs. Future research should focus on elucidating their molecular mechanisms, particularly long non-coding RNAs as well as circular RNAs and sepsis, to further understanding of the disease process. With the in-depth understanding of the mechanism of sepsis, non-coding RNAs provide a new insight into sepsis and could become the novel therapeutic targets in the future.
| S-EPMC5710963 | biostudies-literature
Project description:Skeletal muscle depletion is common in patients with advanced cancer and may be associated with a poor outcome. To investigate whether the changes in skeletal muscle in metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy are associated with clinical outcome, we undertook an observational cohort study using data from a number of randomized clinical trials previously conducted at the Fudan University Shanghai Cancer Center. The muscle mass was evaluated by comparing computed tomography images obtained at baseline with those obtained after 3-4 months of treatment. A total 101 patients were included in the study. The mean skeletal muscle area reduced from 41.6?cm2/m2 to 39.9?cm2/m2 after 3-4 months of targeted therapy. In multivariable analyses adjusted for the number of baseline covariates, muscle loss ?5% was shown to be a significant prognostic factor for both progression-free (hazard ratio [HR]: 1.744, 95% confidence interval [CI]: 1.077-2.826, P?=?0.024) and overall survival (HR: 2.367, 95%CI: 1.253-4.469, P?=?0.008). The addition of muscle loss to the Heng model significantly improved its discriminative ability. In summary, early skeletal muscle loss is frequently observed in mRCC patients and can add prognostic information to current clinical risk scores.
| S-EPMC5548774 | biostudies-literature