The role of human rights and environmental due diligence legislation in protecting women migrant workers in global food supply chains

This research policy study examines the role of human rights and environmental due diligence legislation in protecting women migrant workers in global food supply chains. It considers in detail a recent proposal by the European Parliament for an EU Directive on Corporate Due Diligence and Corporate Accountabilit

Suppressor of Cytokine Signaling-3 (SOCS-3) induces Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) expression in hepatic HepG2 cell line

The suppressor of cytokine signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway activated by proinflammatory cytokines, including the tumor necrosis factor (TNF-\u3b1). SOCS3 is also implicated in hypertriglyceridemia associated to insulin resistance. Proprotein convertase subtilisin kexin type 9 (PCSK9) levels are frequently found to be positively correlated to insulin resistance and plasma very low density lipoprotein (VLDL) triglycerides concentrations. The present study aimed to investigate the possible role of TNF-\u3b1 and JAK/STAT pathway on de novo lipogenesis and PCSK9 expression in HepG2 cells. TNF-\u3b1 induced both SOCS3 and PCSK9 in a concentration-dependent manner. This effect was inhibited by transfection with siRNA anti-STAT3, suggesting the involvement of the JAK/STAT pathway. Retroviral overexpression of SOCS3 in HepG2 cells (HepG2SOCS3) strongly inhibited STAT3 phosphorylation and induced PCSK9 mRNA and protein, with no effect on its promoter activity and mRNA stability. Consistently, siRNA anti-SOCS3 reduced PCSK9 mRNA levels, whereas an opposite effect was observed with siRNA anti- STAT3. In addition, HepG2SOCS3 express higher mRNA levels of key enzymes involved in the de novo lipogenesis, such as fattyacid synthase, stearoyl-CoA desaturase (SCD)-1, and apoB. These responses were associated with a significant increase of SCD-1 protein, activation of sterol regulatory element-binding protein-1c (SREBP-1), accumulation of cellular triglycerides, and secretion of apoB. HepG2SOCS3 show lower phosphorylation levels of insulin receptor substrate 1 (IRS-1) Tyr896 and Akt Ser473 in response to insulin. Finally, insulin stimulation produced an additive effect with SOCS3 overexpression, further inducing PCSK9, SREBP-1, fatty acid synthase, and apoB mRNA. In conclusion, our data candidate PCSK9 as a gene involved in lipid metabolism regulated by proinflammatory cytokine TNF- in a SOCS3-dependent manner

High Density Lipoproteins Inhibit Oxidative Stress-Induced Prostate Cancer Cell Proliferation

Recent evidence suggests that oxidative stress can play a role in the pathogenesis and the progression of prostate cancer (PCa). Reactive oxygen species (ROS) generation is higher in PCa cells compared to normal prostate epithelial cells and this increase is proportional to the aggressiveness of the phenotype. Since high density lipoproteins (HDL) are known to exert antioxidant activities, their ability to reduce ROS levels and the consequent impact on cell proliferation was tested in normal and PCa cell lines. HDL significantly reduced basal and H2O2-induced oxidative stress in normal, androgen receptor (AR)-positive and AR-null PCa cell lines. AR, scavenger receptor BI and ATP binding cassette G1 transporter were not involved. In addition, HDL completely blunted H2O2-induced increase of cell proliferation, through their capacity to prevent the H2O2-induced shift of cell cycle distribution from G0/G1 towards G2/M phase. Synthetic HDL, made of the two main components of plasma-derived HDL (apoA-I and phosphatidylcholine) and which are under clinical development as anti-atherosclerotic agents, retained the ability of HDL to inhibit ROS production in PCa cells. Collectively, HDL antioxidant activity limits cell proliferation induced by ROS in AR-positive and AR-null PCa cell lines, thus supporting a possible role of HDL against PCa progression

PCSK9 induces a pro-inflammatory response in macrophages

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250\u2009\uf7\u20092.5\u2009\ub5g/ml) of human recombinant PCSK9 (hPCSK9). After 24\u2009h incubation with 2.5\u2009\ub5g/ml PCSK9, a significant induction of IL-1\u3b2, IL-6, TNF-\u3b1, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-\u3b1 (2.4\u2009\ub1\u20090.5 fold) and IL-1\u3b2 (8.6\u2009\ub1\u20091.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-\u3b1 mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3\u2009\ub1\u20091.6 fold vs 31.1\u2009\ub1\u20096.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-\u3b1 plasma levels of healthy adult subjects (males 533, females 537) was observed (B\u2009=\u20098.73, 95%CI 7.54\u2009\uf7\u20099.93, p\u2009<\u20090.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR

By the sound of it:an ERP investigation of human action sound processing in 7-month-old infants

Recent evidence suggests that human adults perceive human action sounds as a distinct category from human vocalizations, environmental, and mechanical sounds, activating different neural networks (Engel et al., 2009 and Lewis et al., 2011). Yet, little is known about the development of such specialization. Using event-related potentials (ERP), this study investigated neural correlates of 7-month-olds’ processing of human action (HA) sounds in comparison to human vocalizations (HV), environmental (ENV), and mechanical (MEC) sounds. Relative to the other categories, HA sounds led to increased positive amplitudes between 470 and 570 ms post-stimulus onset at left anterior temporal locations, while HV led to increased negative amplitudes at the more posterior temporal locations in both hemispheres. Collectively, human produced sounds (HA + HV) led to significantly different response profiles compared to non-living sound sources (ENV + MEC) at parietal and frontal locations in both hemispheres. Overall, by 7 months of age human action sounds are being differentially processed in the brain, consistent with a dichotomy for processing living versus non-living things. This provides novel evidence regarding the typical categorical processing of socially relevant sounds

Effects in short and long term of global postural reeducation (GPR) on chronic low back pain: A controlled study with one-year follow-up

Objective. Comparing global postural reeducation (GPR) to a standard physiotherapy treatment (PT) based on active exercises, stretching, and massaging for improving pain and function in chronic low back pain (CLBP) patients. Design. Prospective controlled study. Setting. Outpatient rehabilitation facility. Participants. Adult patients with diagnosis of nonspecific, chronic (>6 months) low back pain. Interventions. Both treatments consisted of 15 sessions of one hour each, twice a week including patient education. Measures. Roland Morris Disability Questionnaire to evaluate disability, and Numeric Analog Scale for pain. A score change >30% was considered clinically significant. Past treatments, use of medications, smoking habits, height, weight, profession, and physical activity were also recorded on baseline, on discharge, and 1 year after discharge (resp., T0, T1, and T2). Results. At T0 103 patients with cLBP (51 cases and 52 controls) were recruited. The treatment (T1) has been completed by 79 (T1) of which 60 then carried out the 1-year follow-up (T2). Both GPR and PT at T1 were associated with a significant statistical and clinical improvement in pain and function, compared to T0. At T2, only pain in GPR still registered a statistically significant improvement

Gender-specific Anatomical Distribution of Internal Pudendal Artery Perforator: A Radiographic Study for Perineal Reconstruction

Background: Cancer, trauma, infection, or radiation can cause perineal defects. Fasciocutaneous flaps based on perforator vessels (PV) from the internal pudendal artery (IPA) provide an ideal reconstructive option for moderate defects. We hypothesized that, due to gender differences in the pelvic-perineal region, the anatomical distribution of PV differs between genders. Methods: Computed tomography angiographies from male and female patients without pelvic-perineal pathologies were retrospectively analyzed to study the vascular anatomy of the IPA. The number, size, type, and distribution of PV were recorded and compared between genders. Four anatomical regions were defined to describe the distribution of PV on each perineal side: anterior (A), anterior-central (AC), central-posterior (CP), and posterior (P). Results: A total of 63 computed tomography angiographies were analyzed (men, 31; women, 32). Each IPA provides 2 +/- 1 PV and 5 +/- 2 terminal (cutaneous) branches: in both genders, 85% of PV are septocutaneous (15% musculocutaneous). In women, 70.5% of PV are located in AC, 28.2% in CP, 1.2% in A, and 0% in P: average diameter of the PV is 2.4 +/- 0.3 mm. In men, 53.7% of PV are located in CP, 43.1% in AC, 3.3% in A, and 0% in P: average diameter of the PV is 2.8 +/- 0.5 mm. Gender-specific differences in anatomical distribution of PV are significant (P \u3c 0.001). Conclusions: Number, size, and type of terminal branches of PV of the IPA are consistent between genders, but their distribution is different, with women having an anterior predominance. Knowledge of gender-specific anatomy can guide preoperative planning and intraoperative dissection in flap-based perineal reconstruction