Effects of Blood-Derived Products on Cellular Senescence and Inflammatory Response: A Study on Skin Rejuvenation.

Blood-derived products, such as citrate platelet-rich plasma (CPRP) and hyperacute serum (HAS), are recognized for their rich growth factor content. When human dermal fibroblast (HDF) cells are exposed to combined mitogenic and DNA-damaging stimuli, it can lead to an increased burden of senescent cells and a modified senescence-associated secretory phenotype. In this study, the senescent state was comprehensively assessed through various methods, including phosphorylated histone H2AX (γH2AX) staining, p21 and p16 q-PCR, p21-western blot, growth curves, and senescence-associated ß-galactosidase staining. Two primary treatments with blood products were administered, one early (immediately after etoposide) and the other late (11 days after etoposide treatment). The effects of the blood product treatment were evaluated by measuring interleukin 6 and 8 (IL-6 and IL-8) levels, as well as collagen 1 (COL1) and p21 mRNA expression. Additionally, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays, cell size measurements, viability assays, and cell number calculations were conducted. The results revealed that cells treated with hyperacute serum in the early treatment phase exhibited the lowest observed IL-6 and IL-8 levels. In contrast, a clear inflammatory response for IL-8 was observed in cells treated with hyperacute serum and citrate platelet-rich plasma during the late treatment. Furthermore, an upregulation of COL1 expression was observed in the early treatment, while cells in the late treatment group remained unaffected. Notably, citrate platelet-rich plasma-treated cells showed a decrease in COL1 expression. Overall, the treatment with blood products appears to have slightly positive effects on skin rejuvenation.

Hemodiafiltration for children with stage 5 chronic kidney disease: technical aspects and outcomes.

Despite significant medical and technical improvements in the field of dialysis, the morbidity and mortality among patients with chronic kidney disease (CKD) stage 5 on dialysis remains extremely high. Hemodiafiltration (HDF), a dialysis method that combines the two main principles of hemodialysis (HD) and hemofiltration-diffusion and convection-has had a positive impact on survival when delivered with a high convective dose. Improved outcomes with HDF have been attributed to the following factors: HDF removes middle molecular weight uremic toxins including inflammatory cytokines, increases hemodynamic stability, and reduces inflammation and oxidative stress compared to conventional HD. Two randomized trials in adults have shown improved survival with HDF compared to high-flux HD. A large prospective cohort study in children has shown that HDF attenuated the progression of cardiovascular disease, improved bone turnover and growth, reduced inflammation, and improved blood pressure control compared to conventional HD. Importantly, children on HDF reported fewer headaches, dizziness, and cramps; had increased physical activity; and improved school attendance compared to those on HD. In this educational review, we discuss the technical aspects of HDF and results from pediatric studies, comparing outcomes on HDF vs. conventional HD. Convective volume, the cornerstone of treatment with HDF and a key determinant of outcomes in adult randomized trials, is discussed in detail, including the practical aspects of achieving an optimal convective volume.

A MATLAB Toolbox for Findable, Accessible, Interoperable, and Reusable Atom Probe Data Science.

Atom probe tomography (APT) data analytics have traditionally been based on manual analytics by researchers. As newer atom probes together with focused ion beam-based specimen preparation have opened APT to many more materials, yielding much more complex mass spectra, building up a systematic understanding of the pathway from raw data to final interpretation has increasingly become important. This demands a system in which the data and treatment can be traced, ideally by any interested party. Such an approach of findable, accessible, interoperable, and reusable (FAIR) data and analysis policies is becoming increasingly important, not just in APT. In this paper, we present a toolbox, written in MATLAB, which allows the user to store the raw and processed data in a standardized FAIR format (hierarchical data format 5) and process the data in a largely scriptable environment to minimize manual user input. This allows for the experiment data to be interchanged without owner explanations and the analysis to be reproduced. We have devised a metadata scheme that is extensible to other experiments in the materials science domain. With this toolbox, collective knowledge can be built up, and a large number of data sets can be analyzed in a fully automated fashion.

Biochemical Characteristics and Potential Biomedical Applications of Hydrolyzed Carrageenans.

Seaweed contains a variety of bioactive compounds; the most abundant of them are polysaccharides, which have significant biological and chemical importance. Although algal polysaccharides, especially the sulfated polysaccharides, have great potential in the pharmaceutical, medical and cosmeceutical sectors, the large molecular size often limits their industrial applications. The current study aims to determine the bioactivities of degraded red algal polysaccharides by several in vitro experiments. The molecular weight was determined by size-exclusion chromatography (SEC), and the structure was confirmed by FTIR and NMR. In comparison to the original furcellaran, the furcellaran with lower molecular weight had higher OH scavenging activities. The reduction in molecular weight of the sulfated polysaccharides resulted in a significant decrease in anticoagulant activities. Tyrosinase inhibition improved 2.5 times for hydrolyzed furcellaran. The alamarBlue assay was used to determine the effects of different Mw of furcellaran, κ-carrageenan and ι-carrageenan on the cell viability of RAW264.7, HDF and HaCaT cell lines. It was found that hydrolyzed κ-carrageenan and ι-carrageenan enhanced cell proliferation and improved wound healing, whereas hydrolyzed furcellaran did not affect cell proliferation in any of the cell lines. Nitric oxide (NO) production decreased sequentially as the Mw of the polysaccharides decreased, which indicates that hydrolyzed κ-Carrageenan, ι-carrageenan and furcellaran have the potential to treat inflammatory disease. These findings suggested that the bioactivities of polysaccharides were highly dependent on their Mw, and the hydrolyzed carrageenans could be used in new drug development as well as cosmeceutical applications.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study.

BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

Chemical Profiling and Bioactivity Assessment of Helichrysum italicum (Roth) G. Don. Essential Oil: Exploring Pure Compounds and Synergistic Combinations.

Helichrysum italicum (Roth) G. Don., immortelle, is a plant species used in ethnomedicine and the food industry as a spice added to food, beverages, and bakery products. It has been shown to possess various biological activities, such as antioxidant and antibacterial activity, making it useful as a natural preservative. We investigated the phytochemical profile and biological activity of H. italicum essential oils from wild-grown plant material collected from natural habitats in the Republic of Croatia and Bosnia and Herzegovina. Using high-resolution scanning electron microscopy (SEM), a visual investigation of plant organs (stem, leaf, and flower) was performed, confirming the presence of essential oil reservoirs on the surface of all examined plant organs. Essential oils were isolated by hydrodistillation in the Clevenger apparatus. The chemical composition of the essential oils was determined using the GC-MS analytical technique. Cytotoxic activity tests were performed in vitro on three cell lines: skin (fibroblast), lung, and breast cancer. Using statistical tools, the synergistic and selective effects of H. italicum essential oil on healthy and tumor cells were correlated to chemical composition and cytotoxic activity. The synergistic and antagonistic effects of H. italicum essential oil's individual components were simulated by testing pure compounds and their mixture of cytotoxic activity on fibroblasts and breast cancer cells. The results confirm that essential oil's biological activity is much greater than the sum of the effects of its components. The present data are novel contributions to the body of knowledge on the biological activity of this species used in the food industry.

scDIOR: single cell RNA-seq data IO software.

BACKGROUND: Single-cell RNA sequencing is becoming a powerful tool to identify cell states, reconstruct developmental trajectories, and deconvolute spatial expression. The rapid development of computational methods promotes the insight of heterogeneous single-cell data. An increasing number of tools have been provided for biological analysts, of which two programming languages- R and Python are widely used among researchers. R and Python are complementary, as many methods are implemented specifically in R or Python. However, the different platforms immediately caused the data sharing and transformation problem, especially for Scanpy, Seurat, and SingleCellExperiemnt. Currently, there is no efficient and user-friendly software to perform data transformation of single-cell omics between platforms, which makes users spend unbearable time on data Input and Output (IO), significantly reducing the efficiency of data analysis. RESULTS: We developed scDIOR for single-cell data transformation between platforms of R and Python based on Hierarchical Data Format Version 5 (HDF5). We have created a data IO ecosystem between three R packages (Seurat, SingleCellExperiment, Monocle) and a Python package (Scanpy). Importantly, scDIOR accommodates a variety of data types across programming languages and platforms in an ultrafast way, including single-cell RNA-seq and spatial resolved transcriptomics data, using only a few codes in IDE or command line interface. For large scale datasets, users can partially load the needed information, e.g., cell annotation without the gene expression matrices. scDIOR connects the analytical tasks of different platforms, which makes it easy to compare the performance of algorithms between them. CONCLUSIONS: scDIOR contains two modules, dior in R and diopy in Python. scDIOR is a versatile and user-friendly tool that implements single-cell data transformation between R and Python rapidly and stably. The software is freely accessible at https://github.com/JiekaiLab/scDIOR .

Precision requirements and data compression in CryoEM/CryoET.

With larger, higher speed detectors and improved automation, individual CryoEM instruments are capable of producing a prodigious amount of data each day, which must then be stored, processed and archived. While it has become routine to use lossless compression on raw counting-mode movies, the averages which result after correcting these movies no longer compress well. These averages could be considered sufficient for long term archival, yet they are conventionally stored with 32 bits of precision, despite high noise levels. Derived images are similarly stored with excess precision, providing an opportunity to decrease project sizes and improve processing speed. We present a simple argument based on propagation of uncertainty for safe bit truncation of flat-fielded images combined with lossless compression. The same method can be used for most derived images throughout the processing pipeline. We test the proposed strategy on two standard, data-limited CryoEM data sets, demonstrating that these limits are safe for real-world use. We find that 5 bits of precision is sufficient for virtually any raw CryoEM data and that 8-12 bits is sufficient for intermediate averages or final 3-D structures. Additionally, we detail and recommend specific rules for discretization of data as well as a practical compressed data representation that is tuned to the specific needs of CryoEM.

Fine-Dust-Induced Skin Inflammation: Low-Molecular-Weight Fucoidan Protects Keratinocytes and Underlying Fibroblasts in an Integrated Culture Model.

Prolonged exposure to fine dust (FD) increases the risk of skin inflammation. Stimulated epidermal cells release growth factors into their extracellular environment, which can induce inflammation in dermal cells. Algae are considered rich sources of bioactive materials. The present study emphasized the effect of low-molecular-weight fucoidan isolated from Sargassum confusum (LMF) against FD-induced inflammation in HaCaT keratinocytes and underneath fibroblasts (HDFs) in an integrated culture model. HDFs were treated with media from FD-stimulated HaCaT with LMF treatments (preconditioned media). The results suggested that FD increased the oxidative stress in HaCaT, thereby increasing the sub-G1 phase of the cell cycle up to 587%, as revealed via flow cytometric analysis. With preconditioned media, HDFs also displayed oxidative stress; however, the increase in the sub-G1 phase was insignificant compared with HaCaT. LMF dose-dependently regulated the NF-κB/MAPK signaling in HaCaT. Furthermore, significant downregulation in NF-κB/MAPK signaling, as well as inflammatory cytokines, tissue inhibitors of metalloproteinases, matrix metalloproteinases, and reduction in relative elastase and collagenase activities related to the extracellular matrix degeneration were observed in HDFs with a preconditioned media treatment. Therefore, we concluded that HDFs were protected from inflammation by preconditioned media. Continued research on tissue culture and in vivo studies may reveal the therapeutic potential of LMF.

mzMLb: A Future-Proof Raw Mass Spectrometry Data Format Based on Standards-Compliant mzML and Optimized for Speed and Storage Requirements.

With ever-increasing amounts of data produced by mass spectrometry (MS) proteomics and metabolomics, and the sheer volume of samples now analyzed, the need for a common open format possessing both file size efficiency and faster read/write speeds has become paramount to drive the next generation of data analysis pipelines. The Proteomics Standards Initiative (PSI) has established a clear and precise extensible markup language (XML) representation for data interchange, mzML, receiving substantial uptake; nevertheless, storage and file access efficiency has not been the main focus. We propose an HDF5 file format "mzMLb" that is optimized for both read/write speed and storage of the raw mass spectrometry data. We provide an extensive validation of the write speed, random read speed, and storage size, demonstrating a flexible format that with or without compression is faster than all existing approaches in virtually all cases, while with compression is comparable in size to proprietary vendor file formats. Since our approach uniquely preserves the XML encoding of the metadata, the format implicitly supports future versions of mzML and is straightforward to implement: mzMLb's design adheres to both HDF5 and NetCDF4 standard implementations, which allows it to be easily utilized by third parties due to their widespread programming language support. A reference implementation within the established ProteoWizard toolkit is provided.

Butylcycloheptylprodigiosin and undecylprodigiosin are potential photosensitizer candidates for photodynamic cancer therapy.

BACKGROUND: Prodiginines are bacterial red polypyrrole pigments and multifaceted secondary metabolites. These agents have anti-proliferative, immunosuppressive, antimicrobial, and anticancer effects. Recent analysis revealed that prodigiosin hypersensitizes Serratia marcescens to gamma radiation. In the present study, we report the cytotoxicity and genotoxicity properties of undecylprodigiosin and butylcycloheptylprodigiosin in the presence and absence of radiation through the MTT and alkaline comet experiments. METHODS AND RESULTS: Findings demonstrated that undecylprodigiosin was at least a fivefold more cytotoxic at low radiation doses (1 and 3 Gy) on both MCF7 and HDF lines rather than in the absence or high radiation doses (5 Gy) (P value < 0.05). Although butylcycloheptylprodigiosin toxicity on MCF7 and HDF was dose-dependent, it was not influenced by any radiation doses (P value > 0.05). Comet findings confirmed that these compounds' genotoxicity is only dose-dependent. Radiation had no significant effects on DNA damage on any of the cells (P value > 0.05). CONCLUSIONS: In general, it can be concluded that the prodiginines are cytotoxic agents that act as a double-edged sword, radiosensitizers and radio-protective, respectively at low and high radiation doses in cancer treatment process. As the results they could be used in antitumor therapies very soon.

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study.

BACKGROUND: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). METHODS: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile. RESULTS: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (ß = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (ß = 0.13 [95%CI 0.06-0.19]; p = 0.0003). CONCLUSIONS: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.

Intra- and interspecies comparison of EYS transcripts highlights its characteristics in the eye.

Inherited mutations in the eyes shut homolog (EYS) gene cause retinitis pigmentosa. Although knock out of eys in zebrafish is pathogenic, the molecular function of EYS in vertebrate photoreceptors is poorly understood. Here, we show that the 5' portion of EYS is eye-specific across vertebrates. We previously determined that a 3' fragment of EYS with an unknown transcription start site is expressed in human dermal fibroblasts (HDF). To obtain insights into the molecular function of EYS in vertebrate photoreceptors, we extensively analyzed EYS (eys) expression in the human fibroblast cell line HDF-adult (HDF-a), the Y79 retinoblastoma cell line, and in zebrafish eyes using rapid amplification of cDNA end, cap analysis of gene expression, RNA sequencing, and RT-PCR. In HDF-a cells, we identified a novel transcript variant (tv), tv5, transcribed from exon 37. In Y79 cells and zebrafish eyes, EYS (eys) was predominantly transcribed from exon 1 or 2, whereas it was transcribed exclusively from exon 37 in HDF-a cells. In the zebrafish eye, there were splice variants that introduced stop codons, resulting in complete loss of the 3' portion of the RNA. These comparative approaches indicate that the 5' portion of the EYS (eys) mRNA appears to be photoreceptor-specific and that the compositions of the deduced EYS proteins in the eye are well-conserved across vertebrates.-Takita, S., Miyamoto-Matsui, K., Seko, Y. Intra- and interspecies comparison of EYS transcripts highlights its characteristics in the eye.

Long-term effects of citric acid-based bicarbonate haemodialysis on patient outcomes: a survival propensity score-matched study in western France.

BACKGROUND: Citric acid-based bicarbonate haemodialysis (CIT-HD) has gained more clinical acceptance over the last few years in France and is a substitute for other acidifiers [e.g. acetic acid (CH3COOH) and hydrochloric acid (HCl)]. This trend was justified by several clinical benefits compared with CH3COOH as well as the desire to avoid the consequences of the corrosive action of HCl, but a nationwide clinical report raised concerns about the long-term safety of CIT-HD. The aim of this study was to assess the long-term effects of CIT-HD exposure on patient outcomes in western France. METHODS: This is a population-based retrospective multicentre observational study performed in 1132 incident end-stage kidney disease patients in five sanitary territories in western France who started their renal replacement therapy after 1 January 2008 and followed up through 15 October 2018. Relevant data, collected prospectively with the same medical software, were anonymously aggregated for the purposes of the study. The primary goal of this study was to investigate the effects of citrate exposure on all-cause mortality. To provide a control group to CIT-HD one, propensity score matching (PSM) at 2:1 was performed in two steps: the first analysis was intended to be exploratory, comparing patients who received citrate ≤80% of the time (CIT-HD ≤80) versus those who received citrate >80% of the time (CIT-HD >80), while the second analysis was intended to be explanatory in comparing patients with 0% (CIT-HD0) versus 100% citrate time exposure (CIT-HD100). RESULTS: After PSM, in the exploratory part of the analysis, 432 CIT-HD ≤80 patients were compared with 216 CIT-HD >80 patients and no difference was found for all-cause mortality using the Kaplan-Meier model (log-rank 0.97), univariate Cox regression analysis {hazard ratio [HR] 1.01 [95% confidence interval (CI) 0.71-1.40]} and multivariate Cox regression analysis [HR 1.11 (95% CI 0.76-1.61)] when adjusted for nine variables with clinical pertinence and high statistical relevance in the univariate analysis. In the explanatory part of the analysis, 316 CIT-HD0 patients were then compared with 158 CIT-HD100 patients and no difference was found using the Kaplan-Meier model (log-rank 0.06), univariate Cox regression analysis [HR 0.69 (95% CI 0.47-1.03)] and multivariate Cox regression analysis [HR 0.87 (95% CI 0.57-1.33)] when adjusted for seven variables with clinical pertinence and high statistical relevance in the univariate analysis. CONCLUSIONS: Findings of this study support the notion that CIT-HD exposure ≤6 years has no significant effect on all-cause mortality in HD patients. This finding remains true for patients receiving high-volume online haemodiafiltration, a modality most frequently prescribed in this cohort.

Online hemodiafilteration use in children: a single center experience with a twist.

BACKGROUND: Haemodiafilteration (HDF) is a promising new modality of renal replacement therapy (RRT). It is an improvement in the quality of hemodialysis (HD) and thus in the quality of patients'lives. The main obstacle to using HDF is the cost, especially in developing countries. The purpose of this study was to evaluate the benefits of incorporating HDF with different regimens in the treatment of children with end stage renal disease (ESRD). METHODS: Thirty-four children with ESRD on regular HD in Pediatric Dialysis Unit, Children's Hospital, Ain Shams University were followed up in 2 phases: initial phase (all patients: HD thrice weekly for 3 months) and second phase, patients were randomized into 2 groups, HDF group and HD group, the former was subdivided into once and twice weekly HDF subgroups. Evaluation using history, clinical and laboratory parameters at 0, 3, 9 and 18 months was carried out. RESULTS: On short term, we found that the HDF group was significantly superior to HD group regarding all clinical and laboratory parameters. Also, twice HDF subgroup was significantly superior to once HDF subgroup. This was confirmed on long term follow up, but the once HDF proved comparable to twice subgroup. CONCLUSIONS: Incorporating online hemodiafilteration (OL-HDF) in the RRT of children was beneficial in most of the clinical and laboratory parameters measured. It's not all or non; OL-HDF, even once a week, can improve outcomes of HD without significantly affecting the cost.

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

BACKGROUND: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. METHODS: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. RESULTS: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher ß2-microglobulin. The HDF cohort had lower ß2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. CONCLUSIONS: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.

Anticatabolic and Anti-Inflammatory Effects of Myricetin 3-O-ß-d-Galactopyranoside in UVA-Irradiated Dermal Cells via Repression of MAPK/AP-1 and Activation of TGFß/Smad.

UV irradiation is one of the main causes of extrinsic skin aging. UV-mediated skin aging, also known as photoaging, causes excessive breakdown of extracellular matrix which leads skin to lose its elasticity and strength. Several phytochemicals are known to exert anti-photoaging effects via different mechanisms, partly due to their antioxidant properties. The current study has been carried out to determine the potential anti-photoaging properties of myricetin 3-O-ß-d-galacto-pyranoside (M3G), a flavonol glycoside isolated from L. tetragonum, in UVA-irradiated in vitro models; HaCaT keratinocytes and human dermal fibroblasts (HDFs). UVA-induced changes in MMP-1 and collagen production have been observed in HaCaT keratinocytes and HDFs. Further, UVA-induced activation of MAPK signaling, and pro-inflammatory cytokine production have been investigated. TGFß/Smad pathway has also been analyzed in UVA-irradiated HDFs. Treatment with M3G reversed the UVA-induced changes in MMP-1 and collagen production both in HaCaT keratinocytes and HDFs. UVA-mediated activation of p38, ERK and JNK MAPK activation was also inhibited by M3G treatment in HaCaT keratinocytes. In HDFs, M3G was able to upregulate the TGFß/Smad pathway activation. In addition, M3G downregulated the UVA-induced pro-inflammatory cytokines in keratinocytes and HDFs. It has been suggested that the M3G has exerted potential antiphotoaging properties in vitro, by attenuating UVA-induced changes in MMP-1 and collagen production in keratinocytes and dermal fibroblasts.

Design and methodology of the impact of HemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFIT trial) in Brazil.

BACKGROUND: End stage renal disease (ESRD) patients require a renal replacement therapy (RRT) to filter accumulated toxins and remove excess water, which are associated with impaired physical function. Hemodialysis (HD) removes middle-molecular weight (MMW) toxins less efficiently compared to hemodiafiltration (HDF); we hypothesized HDF may improve physical function. We detailed the design and methodology of the HDFIT protocol that is testing whether changing from HD to HDF effects physical activity levels and various outcomes. METHODS: HDFIT is a prospective, multi-center, unblinded, randomized control trial (RCT) investigating the impact of dialysis modality (HDF verses HD) on objectively measured physical activity levels, self-reported quality of life, and clinical/non-clinical outcomes. Clinically stable patients with HD vintage of 3 to 24 months without any severe limitation ambulation were recruited from sites throughout southern Brazil. Eligible patients were randomized in a 1:1 ratio to either: 1) be treated with high volume online HDF for 6 months, or 2) continue being treated with high-flux HD. This study includes run-in and randomization visits (baseline), 3- and 6-month study visits during the interventional period, and a 12-month observational follow up. The primary outcome is the difference in the change in steps per 24 h on dialysis days from baseline to the 6-month follow up in patients treated with HDF versus HD. Physical activity is being measured over one week at study visits with the ActiGraph ( www.actigraphcorp.com ). For assessment of peridialytic differences during the dialysis recovery period, we will analyze granular physical activity levels based on the initiation time of HD on dialysis days, or concurrent times on non-dialysis days and the long interdialytic day. DISCUSSION: In this manuscript, we provide detailed information about the HDFIT study design and methodology. This trial will provide novel insights into peridialytic profiles of physical activity and various self-reported, clinical and laboratory outcomes in ESRD patients treated by high volume online HDF versus high-flux HD. Ultimately, this investigation will elucidate whether HDF is associated with patients having better vitality and quality of life, and less negative outcomes as compared to HD. TRIAL REGISTRATION: Registered on ClinicalTrials.gov on 20 April 2016 ( NCT02787161 ).

Restless legs syndrome effectively treated with constant-pressure predilution online hemodiafiltration.

BACKGROUND: We encountered a case of unstable predilution online HDF due to elevated transmembrane pressure (TMP) when performing constant-speed predilution online hemodiafiltration (HDF) as treatment for restless legs syndrome (RLS) in a dialysis patient. We report the effectiveness of incorporating a newly developed constant-pressure predilution online HDF system as a preventive measure against unstable online HDF and frequent adjustment of settings when treating dialysis patients with RLS. CASE PRESENTATION: A 55-year-old man had suffered from RLS and been undergoing constant-speed online HDF with 45 L target predilution and an ABH-21P hemodiafilter. The symptoms of RLS rated 10 on the International Restless Legs Syndrome Rating Scale (IRLS). The α1-microglobulin (α1-MG) removal rate was only 27.8%, so the hemodiafilter was subsequently replaced with a PEPA hemodiafilter. However, episodes of elevated TMP exceeding 250 mmHg occurred frequently after the replacement and were managed by reducing dialysate flow rate. Therefore, we incorporated a constant-pressure predilution online HDF that maintains TMP below 200 mmHg. The amount of replacement was maintained at approximately 43.5 ± 6.98 L and the α1-MG removal rate was 39.5%, with no need to manually reduce the flow rate. The Alb leakage in dialysate waste was 7.9 g. The patient has maintained an IRLS rating of 0 with no RLS symptoms for the past 4 years. CONCLUSIONS: Using the constant-pressure mode enabled achieved the clinical endpoint, namely, resolution of RLS with no need to manually reduce the flow rate.

The arc of Mass Spectrometry Exchange Formats is long, but it bends toward HDF5.

The evolution of data exchange in Mass Spectrometry spans decades and has ranged from human-readable text files representing individual scans or collections thereof (McDonald et al., 2004) through the official standard XML-based (Harold, Means, & Udemadu, 2005) data interchange standard (Deutsch, 2012), to increasingly compressed (Teleman et al., 2014) variants of this standard sometimes requiring purely binary adjunct files (Römpp et al., 2011). While the desire to maintain even partial human readability is understandable, the inherent mismatch between XML's textual and irregular format relative to the numeric and highly regular nature of actual spectral data, along with the explosive growth in dataset scales and the resulting need for efficient (binary and indexed) access has led to a phenomenon referred to as "technical drift" (Davis, 2013). While the drift is being continuously corrected using adjunct formats, compression schemes, and programs (Röst et al., 2015), we propose that the future of Mass Spectrometry Exchange Formats lies in the continued reliance and development of the PSI-MS (Mayer et al., 2014) controlled vocabulary, along with an expedited shift to an alternative, thriving and well-supported ecosystem for scientific data-exchange, storage, and access in binary form, namely that of HDF5 (Koranne, 2011). Indeed, pioneering efforts to leverage this universal, binary, and hierarchical data-format have already been published (Wilhelm et al., 2012; Rübel et al., 2013) though they have under-utilized self-description, a key property shared by HDF5 and XML. We demonstrate that a straightforward usage of plain ("vanilla") HDF5 yields immediate returns including, but not limited to, highly efficient data access, platform independent data viewers, a variety of libraries (Collette, 2014) for data retrieval and manipulation in many programming languages and remote data access through comprehensive RESTful data-servers. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:668-673, 2017.