Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate ...hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH.
Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4).
HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of
but not
was higher in mouse models and patients with NASH. FC in hepatocytes induced
expression, and
knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of
prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but
knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis.
SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.
Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute ...to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.
Background
Massage and aromatherapy massage are used to relieve cancer‐related symptoms. A number of claims have been made for these treatments including reduction of pain, anxiety, depression, and ...stress. Other studies have not shown these benefits.
Objectives
To evaluate the effects of massage with or without aromatherapy on pain and other symptoms associated with cancer.
Search methods
We searched the following databases and trials registries up to August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 7), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), PubMed Cancer Subset, SADCCT, and the World Health Organization (WHO) ICTRP. We also searched clinical trial registries for ongoing studies.
Selection criteria
Randomised controlled studies (RCTs) reporting the effects of aromatherapy or massage therapy, or both, in people with cancer of any age. We applied no language restrictions. Comparators were massage (using carrier oil only) versus no massage, massage with aromatherapy (using carrier oil plus essential oils) versus no massage, and massage with aromatherapy (using carrier oil plus essential oils) versus massage without aromatherapy (using carrier oil only).
Data collection and analysis
At least two review authors selected studies, assessed the risk of bias, and extracted data relating to pain and other symptoms associated with cancer, using standardised forms. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created two 'Summary of findings' tables.
Main results
We included 19 studies (21 reports) of very low quality evidence with a total of 1274 participants. We included 14 studies (16 reports) in a qualitative synthesis and five studies in a quantitative synthesis (meta‐analysis). Thirteen studies (14 reports, 596 participants) compared massage with no massage. Six studies (seven reports, 561 participants) compared aromatherapy massage with no massage. Two studies (117 participants) compared massage with aromatherapy and massage without aromatherapy. Fourteen studies had a high risk of bias related to sample size and 15 studies had a low risk of bias for blinding the outcome assessment. We judged the studies to be at unclear risk of bias overall. Our primary outcomes were pain and psychological symptoms. Two studies reported physical distress, rash, and general malaise as adverse events. The remaining 17 studies did not report adverse events. We downgraded the GRADE quality of evidence for all outcomes to very low because of observed imprecision, indirectness, imbalance between groups in many studies, and limitations of study design.
Massage versus no‐massage groups
We analysed results for pain and anxiety but the quality of evidence was very low as most studies were small and considered at an unclear or high risk of bias due to poor reporting. Short‐term pain (Present Pain Intensity‐Visual Analogue Scale) was greater for the massage group compared with the no‐massage group (one RCT, n = 72, mean difference (MD) ‐1.60, 95% confidence interval (CI) ‐2.67 to ‐0.53). Data for anxiety (State‐Trait Anxiety Inventory‐state) relief showed no significant difference in anxiety between the groups (three RCTs, n = 98, combined MD ‐5.36, 95% CI ‐16.06 to 5.34). The subgroup analysis for anxiety revealed that the anxiety relief for children was greater for the massage group compared with the no‐massage group (one RCT, n = 30, MD ‐14.70, 95% CI ‐19.33 to ‐10.07), but the size of this effect was considered not clinically significant. Furthermore, this review demonstrated no differences in effects of massage on depression, mood disturbance, psychological distress, nausea, fatigue, physical symptom distress, or quality of life when compared with no massage.
Massage with aromatherapy versus no‐massage groups
We analysed results for pain, anxiety, symptoms relating to the breast, and quality of life but the quality of evidence was very low as studies were generally at a high risk of bias. There was some indication of benefit in the aromatherapy‐massage group but this benefit is unlikely to translate into clinical benefit. The relief of medium‐ and long‐term pain (medium‐term: one RCT, n = 86, MD 5.30, 95% CI 1.52 to 9.08; long‐term: one RCT, n = 86, MD 3.80, 95% CI 0.19 to 7.41), anxiety (two RCTs, n = 253, combined MD ‐4.50, 95% CI ‐7.70 to ‐1.30), and long‐term symptoms relating to the breast in people with breast cancer (one RCT, n = 86, MD ‐9.80, 95% CI ‐19.13 to ‐0.47) was greater for the aromatherapy‐massage group, but the results were considered not clinically significant. The medium‐term quality of life score was lower (better) for the aromatherapy‐massage group compared with the no‐massage group (one RCT, n = 30, MD ‐2.00, 95% CI ‐3.46 to ‐0.54).
Massage with aromatherapy versus massage without aromatherapy groups
From the limited evidence available, we were unable to assess the effect of adding aromatherapy to massage on the relief of pain, psychological symptoms including anxiety and depression, physical symptom distress, or quality of life.
Authors' conclusions
There was a lack of evidence on the clinical effectiveness of massage for symptom relief in people with cancer. Most studies were too small to be reliable and key outcomes were not reported. Any further studies of aromatherapy and massage will need to address these concerns.
Ubiquitination, one of many post-translational modifications, causes proteasome-mediated protein degradation by attaching ubiquitin to target proteins. Multiple deubiquitinases inhibit the ...ubiquitination pathway by removing the ubiquitin chain from protein, thus contributing to the stabilization of substrates. USP41 contributes to invasion, apoptosis and drug resistance in breast and lung cancer cells. However, the detailed mechanism and role of USP41 in breast cancer have not been elucidated. USP41 was overexpressed and showed poor prognosis according to the aggressive phenotype of breast cancer cells. Knockdown of USP41 inhibited migration and growth of breast cancer cells, whereas overexpression of USP41 increased cell growth and migration. In addition, depletion of USP41 downregulated Snail protein expression, an epithelial-mesenchymal transition marker, but not mRNA expression. Furthermore, USP41 interacted with and inhibited ubiquitination of Snail, resulting in the increase in Snail stabilization. Therefore, these data demonstrated that USP41 increases migration of breast cancer cells through Snail stabilization.
During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of ...its target genes regulating glycolytic metabolism. Here, using a skeletal muscle-specific gene ablation mouse model, we show that Brg1/Brm-associated factor 155 (Baf155), a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is essential for HIF-1α signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1α function, which accompanies the decreased lactate production during exercise. Furthermore, the augmented oxidation leads to high intramuscular adenosine triphosphate (ATP) level and results in the enhancement of endurance exercise capacity. Mechanistically, our chromatin immunoprecipitation (ChIP) analysis reveals that Baf155 modulates DNA-binding activity of HIF-1α to the promoters of its target genes. In addition, for this regulatory function, Baf155 requires a phospho-signal transducer and activator of transcription 3 (pSTAT3), which forms a coactivator complex with HIF-1α, to activate HIF-1α signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling.
Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine for bone due to their excellent proliferative capacity and the ability to obtain a ...large number of cells with minimal donor morbidity. On the other hand, the differentiation potential of ASCs is generally lower than that of bone marrow-derived stromal/stem cells and varies greatly depending on donors. In this study, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA-seq gene analysis, we discovered that GSTT1 (Glutathione S-transferase theta-1) was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation. On the other hand, GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species and increased GSH/GSSG ratios were also detected in GSTT1-transfected ASCs. When the in vivo effect of GSTT1-transfected ASCs on bone regeneration was investigated with segmental long-bone defect model in rats, bone regeneration was significantly better after implantation of GSTT1-transfected ASCs compared to that of control vector-transfected ASCs. In conclusion, GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones. This article is protected by copyright. All rights reserved.
Polyphenols are secondary metabolites produced in higher plants. They are known to possess various functional properties in the human body. Polyphenols also exhibit antibacterial activities against ...foodborne pathogens. Their antibacterial mechanism is based on inhibiting bacterial biofilm formation or inactivating enzymes. Food-derived polyphenols with such antibacterial activity are natural preservatives and can be used as an alternative to synthetic preservatives that can cause side effects, such as allergies, asthma, skin irritation, and cancer. Studies have reported that polyphenols have positive effects, such as decreasing harmful bacteria and increasing beneficial bacteria in the human gut microbiota. Polyphenols can also be used as natural antibacterial agents in food packaging system in the form of emitting sachets, absorbent pads, and edible coatings. We summarized the antibacterial activities, mechanisms and applications of polyphenols as antibacterial agents against foodborne bacteria.
Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. ...Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing, next-generation mapping, microfluidics-based linked reads, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.
Sitting for an extended time may cause a serious chronic disease such as a musculoskeletal disorder, or a cardiovascular disease, diabetes, or obesity. Because a consistently improper posture from ...early childhood to adolescence can have a number of undesirable effects on the formation of the musculoskeletal structure, learning to maintain a correct posture should be emphasized. A consistently improper posture can not only cause physical problems, it may also lead to emotional issues such as distractions, an attention deficit, and hyperactivity, and the possibility of a low efficiency and performance on assignments is high when the students have a low concentration. The present study implemented a distracted estimation system based on sensor fusion through correlation analysis with concentration that could estimate the level of distraction and prevent musculoskeletal diseases caused by poor sitting posture habits in daily life. The implemented system was designed in the form of a sitting cushion to reflect the ethological movements and characteristics of a sitting position that modern people spend a large amount of time in, and can be easily applied to existing chairs. Both algorithms installed in the system detected the center of gravity of the seated person and displayed positional changes that occurred based on the intensity of the postural changes when moving; thus, simultaneous determination of posture and impulsive behavior was possible. To evaluate the system performance, a posture determination evaluation was conducted, along with distraction estimation according to the rate of changes in posture that occur in everyday life. In addition, to evaluate performance in daily life, a movie-watching scenario was set up, and the distracted-limit estimation and concentration indices according to the rate of changes in posture were comparatively evaluated by reviewing a video of the subjects. The results of the posture determination performance evaluation through 100 posture repetitions on 10 subjects showed a high detection performance of 99.04%. The Pearson's correlation coefficient results showed a high correlation coefficient (inverse) of r = -0.975076 and a P-VALUE = 1.654 × 10 - 6 . This experiment objectively confirmed the correlation between the DLE Index (based on postural change) and the CI Index (based on EEG).
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