Pedersenherskind9983

Ultra-radical surgery to achieve complete resection in advanced epithelial ovarian cancer (EOC) has been widely accepted without strong supporting data. Our objective was to assess overall survival after a structured shift to an ultra-radical upfront surgical treatment algorithm and to investigate changes in the distribution of primary treatments after this shift.

In this population-based cohort study, all women with suspected EOC in the Stockholm-Gotland region of Sweden reported to the Swedish Quality Registry for Gynecologic Cancer (SQRGC) and National Cancer Registry (NCR) were selected in two 3-year cohorts, based on year of diagnosis (before (cohort1) or after (cohort 2) change in surgical treatment algorithm) and followed for at least three years. 5-year overall survival (OS) in non-surgically and surgically treated women was analyzed. Moreover, proportional distribution of primary treatment was evaluated.

752 women were included in the final analysis (n = 364 and 388 in cohort 1 and 2 respectively) with a median follow-up of 29 and 27 months. The complete resection rate increased from 37 to 67% (p ≤ 0.001) as well as proportion non-surgically treated women, 24 to 33%. No improvement in OS was observed in non-surgically (HR 0.76 (95% CI, 0.58-1.01); p = 0.06) or surgically treated (HR 0.94 (95% CI, 0.75-1.18); p = 0.59) women, even when complete resection was achieved (HR 1.31 (95% CI, 0.89-1.92); p = 0.17).

A shift to ultra-radical upfront surgery in EOC did not improve survival despite a significant increase in complete resection rate. Identifying the limitations of surgical treatment remains a challenge.

A shift to ultra-radical upfront surgery in EOC did not improve survival despite a significant increase in complete resection rate. Identifying the limitations of surgical treatment remains a challenge.Delayed wound healing in diabetes is characterized by sustained activation of inflammasome and increased expression of IL-1β in macrophages. Identification and validation of novel pathways to regulate IL-1β expression will provide therapeutic targets for diabetic wounds. Here we report sustained over-expression of histone deacetylase 6 (HDAC6) in wounds of diabetic mice and its role in delayed wound healing. Topical application of HDAC6 inhibitor; Tubastatin A (TSA) gel promoted the wound healing in diabetic mice. TSA hydrogel reduced the infiltration of neutrophils, T-cells and macrophages in the early phase of wound healing. TSA treatment promoted the wound healing by inducing collagen deposition, angiogenesis (CD31) and fibrotic factors (TGF-β1) in the late phase of healing. Protein analysis of the diabetic wounds treated with TSA showed increased acetylated α-tubulin and decreased levels of mature IL-1β with no significant effect on the expression of pro-IL-1β, pro-caspase-1 and active caspase-1. In in vitro assays, macrophages exhibited upregulation of HDAC6, IL-1β and downregulation of IL-10 upon stimulation with high glucose and LPS. TSA inhibited the IL-1β secretion and promoted IL-10 in stimulated macrophages with high glucose and LPS. Further investigations showed that TSA inhibits IL-1β release by inhibiting tubulin dependent lysosomal exocytosis without affecting its transcription and maturation. Selleckchem APX-115 Nocodazole (known acetylation inhibitor) pre-treatment inhibited TSA effect on IL-1β secretion in high glucose stimulated macrophages. Overall, our findings indicate that sustained HDAC6 expression in diabetic wounds contributes to impaired healing responses and HDAC6 may represent a new therapeutic target for diabetic wounds.Why mitochondria still retain their own genome is a puzzle given the enormous effort to maintain a mitochondrial translation machinery. Most mitochondrially encoded proteins are membrane-embedded subunits of the respiratory chain. Their hydrophobicity presumably impedes their import into mitochondria. However, many mitochondrial genomes also encode protein subunits of the mitochondrial ribosome. These proteins lack transmembrane domains and hydrophobicity cannot explain why their genes remained in mitochondria. In this review, we provide an overview about mitochondrially encoded subunits of mitochondrial ribosomes of fungi, plants and protists. Moreover, we discuss and evaluate different hypotheses which were put forward to explain why (ribosomal) proteins remained mitochondrially encoded. It seems likely that the synthesis of ribosomal proteins in the mitochondrial matrix is used to regulate the assembly of the mitochondrial ribosome within mitochondria and to avoid problems that mitochondrial proteins might pose for cytosolic proteostasis and for the assembly of cytosolic ribosomes.In higher-plant Photosystem I (PSI), the majority of "red" chlorophylls (absorbing at longer wavelengths than the reaction centre P700) are located in the peripheral antenna, but contradicting reports are given about red forms in the core complex. Here we attempt to clarify the spectroscopic characteristics and quantify the red forms in the PSI core complex, which have profound implication on understanding the energy transfer and charge separation dynamics. To this end we compare the steady-state absorption and fluorescence spectra and picosecond time-resolved fluorescence kinetics of isolated PSI core complex and PSI-LHCI supercomplex from Pisum sativum recorded at 77 K. Gaussian decomposition of the absorption spectra revealed a broad band at 705 nm in the core complex with an oscillator strength of three chlorophylls. Additional absorption at 703 nm and 711 nm in PSI-LHCI indicated up to five red chlorophylls in the peripheral antenna. Analysis of fluorescence emission spectra resolved states emitting at 705, 715 and 722 nm in the core and additional states around 705-710 nm and 733 nm in PSI-LHCI. The red states compete with P700 in trapping excitations in the bulk antenna, which occurs on a timescale of ~20 ps. The three red forms in the core have distinct decay kinetics, probably in part determined by the rate of quenching by the oxidized P700. These results affirm that the red chlorophylls in the core complex must not be neglected when interpreting kinetic experimental results of PSI.