Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC.
 
  PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples (
  = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses.
 
  Kaplan-Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, 
  = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, 
  < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, 
  < 0.001) in Kaplan-Meier and in a multivariate Cox regression analyses (HR 2.935 (1.645-5.236), 
  < 0.001).
 
  The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.
 The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.Chronic pain (CP) severely disrupts the daily life of millions. Interoception (i.e., sensing the physiological condition of the body) plays a pivotal role in the aetiology and maintenance of CP. As pain is inherently an interoceptive signal, interoceptive frameworks provide important, but underutilized, approaches to this condition. Here we first investigated three facets of interoceptive perception in CP, compared with pain-free controls. We then introduce a novel interoceptive treatment and demonstrate its capacity to reduce pain severity in CP, potentially providing complementary analgesic treatments. Study 1 measured interoceptive accuracy, confidence and sensibility in patients (N = 60) with primary, secondary musculoskeletal, and neuropathic CP. Compared with matched controls, CP participants exhibited significantly lower interoceptive accuracy and interoceptive confidence. Pain severity was predicted positively by interoceptive accuracy, anxiety and depression, and negatively by interoceptive confidence. Study 2 tested a promising new interoceptive treatment for CP, in a single-blind between-subjects design (N = 51) with primary, secondary musculoskeletal, and neuropathic CP patients. The treatment specifically activates the C-Tactile system, by means of controlled stimulation of interoceptive unmyelinated afferents, at 3 cm/s with a force of 2.5 mN. This treatment led to significant pain reduction (mean 23%) in the CP treatment group after only 11 min, while CP controls who received comparable but non-interoceptive stimulation reported no change in pain intensity. These studies highlight the importance of interoceptive approaches to CP and demonstrate the potential of this novel method of C-Tactile stimulation to provide complementary analgesic treatments.Tumor immune infiltration plays a key role in the progression of solid tumors, including ovarian cancer, and immunotherapies are rapidly emerging as effective treatment modalities. However, the role of cancer-associated fibroblasts (CAFs), a predominant stromal constituent, in determining the tumor-immune microenvironment and modulating efficacy of immunotherapies remains poorly understood. We have conducted an extensive bioinformatic analysis of our and other publicly available ovarian cancer datasets (GSE137237, GSE132289 and GSE71340), to determine the correlation of fibroblast subtypes within the tumor microenvironment (TME) with the characteristics of tumor-immune infiltration. We identified (1) four functional modules of CAFs in ovarian cancer that are associated with the TME and metastasis of ovarian cancer, (2) immune-suppressive function of the collagen 1,3,5-expressing CAFs in primary ovarian cancer and omental metastases, and (3) consistent positive correlations between the functional modules of CAFs with anti-immune response genes and negative correlation with pro-immune response genes. Our study identifies a specific fibroblast subtype, fibroblast functional module (FFM)2, in the ovarian cancer tumor microenvironment that can potentially modulate a tumor-promoting immune microenvironment, which may be detrimental toward the effectiveness of ovarian cancer immunotherapies.Understanding the effects of precipitation variations on plant biochemical and functional traits is crucial to predict plant adaptation to future climate changes. The dominant species, Stipa glareosa, plays an important role in maintaining the structure and function of plant communities in the desert steppe, Inner Mongolia. However, little is known about how altered precipitation affects biochemical and functional traits of S. glareosa in different communities in the desert steppe. Here, we examined the responses of biochemical and functional traits of S.  https://www.selleckchem.com/products/Temsirolimus.html  glareosa in shrub- and grass-dominated communities to experimentally increased precipitation (control, +20%, +40%, and +60%). We found that +40% and +60% increased plant height and leaf dry matter content (LDMC) and decreased specific leaf area (SLA) of S. glareosa in grass community. For biochemical traits in grass community, +60% decreased the contents of protein and chlorophyll b (Cb), while +40% increased the relative electrical conductivity and superoxiof S. glareosa in different plant communities at the same site to precipitation changes.Natural calcium phosphates derived from fish wastes are a promising material for biomedical application. However, their sintered ceramics are not fully characterized in terms of mechanical and biological properties. In this study, natural calcium phosphate was synthesized through a thermal calcination process from salmon fish bone wastes. The salmon-derived calcium phosphates (sCaP) were sintered at different temperatures to obtain natural calcium phosphate bioceramics and then were investigated in terms of their microstructure, mechanical properties and biocompatibility. In particular, this work is concerned with the effects of grain size on the relative density and microhardness of the sCaP bioceramics. Ca/P ratio of the sintered sCaP ranged from 1.73 to 1.52 when the sintering temperature was raised from 1000 to 1300 °C. The crystal phase of all the sCaP bioceramics obtained was biphasic and composed of hydroxyapatite (HA) and tricalcium phosphate (TCP). The density and microhardness of the sCaP bioceramics increased in the temperature interval 1000-1100 °C, while at temperatures higher than 1100 °C, these properties were not significantly altered.