Notes

PPA1 Helps bring about Breast cancers Proliferation as well as Metastasis By means of PI3K/AKT/GSK3β Signaling Path.
Obstructive sleep apnea (OSA) and obesity are increasingly prevalent worldwide. Both promote endothelial dysfunction contributing to systemic and pulmonary hypertension over time. Endothelin-1 (ET-1) plays a pivotal role in the development of pulmonary hypertension (PH). The aim of the present study was to assess the association between plasma ET-1 and echocardiographic findings in obese individuals with and without OSA, as well as in non-obese patients with OSA.

Ninety-seven subjects (56 males) were enrolled in the study. All subjects underwent the following tests venous endothelin-1 levels, pulmonary function testing, and arterial blood gas analysis. All patients except controls underwent transthoracic echocardiography and portable testing for sleep-disordered breathing.

Plasma ET-1 levels were significantly higher in obese patients, both with and without OSA (respectively, n = 30 (mean value, 268.06 ± 49.56pg/ml) and n = 32 (mean value, 263.12 ± 65.26pg/ml)), compared with non-obese patients with OSA or to healthy controls (respectively, n = 20 (mean value, 149.8 ± 23.09pg/ml) and n = 15 (mean value, 152.3 ± 27.64pg/ml); p < 0.0001). Pulmonary artery pressure (PAPs) in obese patients with OSA were significantly higher than in obese patients without OSA (p < 0.0001), while there was no statistical difference between PAPs of obese patients without OSA, compared with the group of non-obese OSA patients. Plasma ET-1 levels significantly correlated with systolic PAPs in obese patients both with and without OSA (respectively, n = 30, r = 0.385, p = 0.03567; n = 32, r = 0.3497, p = 0.0497).

Our study suggests that endothelin levels are more strongly associated with weight than the presence of sleep-disordered breathing, but pulmonary artery hypertension is associated with both weight and OSA.
Our study suggests that endothelin levels are more strongly associated with weight than the presence of sleep-disordered breathing, but pulmonary artery hypertension is associated with both weight and OSA.
Obstructive sleep apnea syndrome (OSAS) has a higher prevalence in postmenopausal women who are not on hormone replacement therapy (HRT), as compared to premenopausal women. Cognitive impairment (CI) is associated with OSAS and the early postmenopausal state. We hypothesized that compared to postmenopausal women at low risk for OSAS, postmenopausal women at high risk for OSAS would report worse cognitive function.

Early postmenopausal women not on HRT between the ages of 45 and 60years, within 5years of natural menopause, were enrolled. Participants completed a REDCap survey which collected information on demographics and risk factors, Berlin questionnaire to screen subjects for OSAS risk, and the Mail-In Cognitive Function Screening Instrument (MCFSI) score which was used to assess CI.

Of 381 respondents, 127 were omitted due to missing/duplicate data or not meeting inclusion criteria. One hundred fifty-four women were classified as high risk for OSAS (OSAS+), and 100 were classified as low risk for OSAS (OSAS-). OSAS- women reported lifetime smoking, lifetime drinking, and recreational drug use more often than OSAS+ women, while OSAS+ women reported a depression diagnosis more often. The mean MCFSI score in the OSAS+ group was significantly higher (worse cognition) than in the OSAS- group after controlling for covariates (5.59, 95% CI 5.08-6.11 vs. 4.29, 95% CI 3.64-4.93, p < 0.05).

Early postmenopausal women at high risk for OSAS report more CI than those at low risk for OSAS. Future studies should identify biomarkers of this CI and define the degree of reversibility of CI with OSAS treatment.
Early postmenopausal women at high risk for OSAS report more CI than those at low risk for OSAS. Future studies should identify biomarkers of this CI and define the degree of reversibility of CI with OSAS treatment.The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features.Triple-negative breast cancer (TNBC) is a unique breast cancer subtype with high heterogeneity and poor prognosis. this website Currently, the treatment effect of TNBC has reached a bottleneck, rendering new breakthroughs difficult. Cancer invasion is not an entirely cell-autonomous process, requiring the cells to transmigrate across the surrounding extracellular matrix (ECM) barriers. Developing a new system that integrates key constituents in the tumor microenvironment with pivotal cancer cell molecules is essential for the in-depth investigation of the mechanism of invasion in TNBC. We describe a computer-aided algorithm developed using quantum dot (QD)-based multiplex molecular imaging of TNBC tissues. We performed in situ simultaneous imaging and quantitative detection of epidermal growth factor receptor (EGFR), expressed in the TNBC cell membrane, and collagen IV, the major ECM constituent; calculated the EGFR/collagen IV ratio; and investigated the prognostic value of the EGFR/collagen IV ratio in TNBC. We simultaneously imaged and quantitatively detected EGFR and collagen IV in the TNBC samples. In all patients, quantitative determination showed a statistically significant negative correlation between EGFR and collagen IV. The 5-year disease-free survival (5-DFS) of the high and low EGFR/collagen IV ratio subgroups was significantly different. The EGFR/collagen IV ratio was predictive and was an independent prognostic indicator in TNBC. Compared with EGFR expression, the EGFR/collagen IV ratio had a greater prognostic value for 5-DFS. Our findings open up a new avenue for predicting the clinical outcome in TNBC from the perspective of integrating molecules expressed in both cancer cells and the ECM.Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. link2 Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. link3 Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.Subcutaneous injection of the tumor cell suspension is a simple and commonly used tool for studying tumor development in vivo. However, subcutaneous models poorly resemble tumor complexity due to the fast growth not reflecting the natural course. Here, we describe an application of the new spheroid-plug model to combine the simplicity of subcutaneous injection with improved resemblance to natural tumor progression. Spheroid-plug model relies on in vitro formation of tumor spheroids, followed by injection of single tumor spheroid subcutaneously in Matrigel matrix. In spheroid-plug model, tumors grow slower in comparison to tumors formed by injection of cell suspension as assessed by 3D ultrasonography (USG) and in vivo bioluminescence measurements. The slower tumor growth rate in spheroid-plug model is accompanied by reduced necrosis. The spheroid-plug model ensures increased and more stable vascularization of tumor than classical subcutaneous tumor model as demonstrated by 3D USG Power Doppler examination. Flow cytometry analysis showed that tumors formed from spheroids have enhanced infiltration of endothelial cells as well as hematopoietic and progenitor cells with stem cell phenotype (c-Kit(+) and Sca-1(+)). They also contain more tumor cells expressing cancer stem cell marker CXCR4. Here, we show that spheroid-plug model allows investigating efficiency of anticancer drugs. Treatment of spheroid-plug tumors with known antiangiogenic agent axitinib decreased their size and viability. The antiangiogenic activity of axitinib was higher in spheroid-plug model than in classical model. Our results indicate that spheroid-plug model imitates natural tumor growth and can become a valuable tool for cancer research.Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. Chondrosarcoma is the most common primary malignant bone tumor in adults and has no effective systemic treatment, and patients with this disease have poor survival. Thus, it is important to find new diagnostic markers and improve treatment options. In the current study, we are interested to examine the role of miR-185 and miR-218 expression in patients with chondrosarcoma using real-time PCR. Moreover, the association of the two miRNAs with clinicopathological features and prognosis was evaluated. Survival and Cox proportional hazards analyses were performed to find the association of miR-185 expression and miR-218 levels with prognosis in the patients. Our results indicated that the miR-185 expression was significantly downexpressed in clinical chondrosarcoma bone tissues compared with adjacent normal tissues (P = 0.001). MiR-218 expression level was increased in clinical chondrosarcoma bone tissue than those adjacent normal tissues (P = 0.
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