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Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.

Background: Job performance is known as an essential reflection of nursing quality. Colleague solidarity, positive emotion, and turnover intention play effective roles in a clinical working environment, but their impacts on job performance are unclear. Investigating the association between nurses’ colleague solidarity and job performance may be valuable, both directly and through the mediating roles of positive emotion and turnover intention. Methods: In this cross-sectional study, a total of 324 Chinese nurses were recruited by convenience sampling method from July 2016 to January 2017. Descriptive analysis, Spearman’s correlation analysis, and the structural equation model were applied for analysis by SPSS 26.0 and AMOS 24.0. Results: A total of 49.69% of participants were under 30 years old, and 90.12% of participants were female. Colleague solidarity and positive emotion were positively connected with job performance. The results indicated the mediating effects of positive emotion and turnover intention in this relationship, respectively, as well as the chain mediating effect of positive emotion and turnover intention. Conclusions: In conclusion, dynamic and multiple supportive strategies are needed for nurse managers to ameliorate nursing job performance by improving colleague solidarity and positive emotion and decreasing turnover intention based on the job demand-resource model.

ABSTRACTObjective Long non-coding RNAs (lncRNAs) are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in extramedullary disease of multiple myeloma (EMD), we analyzed the expression profile of lncRNAs in EMD.Methods Three pairs of EMD patients and their intramedullary MM cells were screened by microarray first. We extracted data from gene chips and made an identification of lncRNAs and mRNAs with significant differences between EMD group and non EMD group. WGCNA confirmed the EMD related gene module and drew a heat map to further determine the key gene lncRNA-NEAT1. In the meantime, bone marrow and extramedullary samples (hydrothorax and ascites) were collected from 2 MM patients and subjected to single-cell RNA-seq. Single cell Transcriptome analysis was conducted to verify the gene expression difference of malignant plasma cells derived from intramedullary and extramedullary. Then we verified high expression level of lncRNA-NEAT1 in EMD patients by using quantitative real-time PCR (qRT-PCR) and analyzed the correlation between expression patterns and survival and molecular genetics analysis of the LncRNA (NEAT1) involved in MM patients. At last, cell experiments were conducted to observe the effects of down-regulation of NEAT1on the proliferation, cell cycle and PTEN pathway related proteins of multiple myeloma cell lines U266 and RPMI8226.Results We identified one of the EMD related key gene is lncRNA-NEAT1. Compared with patients without extramedullary lesions, intramedullary MM cells in EMD patients expressed NEAT1 highly. The outcome of parallel single-cell RNA sequencing (RNA-seq) revealed NEAT1 level of plasma cells came from pleural effusion /ascites increased significantly compared with myeloma-stricken bone marrow. By survival and molecular genetic analysis, NEAT1 gene expression was not associated with OS and PFS in MM patients. However, the expression of NEAT1 is related to adverse therapeutic reactions and the progression of MM. We found that the expressions of NEAT1 were negatively associated with albumin levels and were positively associated with gain of chromosome 1q, IGH-CCND1, IGH@-FGFR3/WHSC1,and IGH-MAF gene fusion, respectively. At the level of cell experiment, CCK-8, soft agar clone formation experiment and CFSE staining showed that down regulating NEAT1 could inhibit the proliferation of U266 and RPMI8226 cells; Cell cycle detection showed that down-regulation of NEAT1 would interfere with the cell cycle process, and RPMI 8226 cells were blocked in G1 phase. Western blot analysis showed that when the expression of NEAT1 was down regulated in U266 and RPMI 8226 cells, the expression of PTEN and p-PTEN (phosphorylated phosphatase and tensin homologue) was up-regulated, and the expression of PI3K, p-PI3K (human phosphorylated inositol 3 kinase), Akt, p-Akt (phosphorylated protein kinase B).Discuccion and conclusion This study provides novel insights into the lncRNA-NEAT1 and reveals that NEAT1 maybe a potential lncRNA biomarkers in EMD.

Abstract Introduction Critical H1N1 pneumonia patients usually have one of the symptoms such as respiratory failure, septic shock, multiple organ dysfunction, or other need for intensive care management, which are associated with high risk of mortality. It is essential to differentiate the severity of H1N1 pneumonia and take corresponding target treatments. Objectives We aim to investigate the differences in clinical characteristics and chest computed tomography (CT) findings between severe and critical patients with H1N1 pneumonia. Methods A total of 27 patients diagnosed with H1N1 pneumonia from October 2018 to March 2019 were retrospectively analyzed, and the differences in clinical manifestations, laboratory tests, and chest CT findings between the severe group (15 patients) and the critical group (12 patients) were compared. Results Frequency of dyspnea at rest was higher in critical group than that in severe group (P = 0.019). The neutrophil percentage was higher (P = 0.014) and the lymphocyte percentage was lower (P = 0.025) in critical compared with severe group. Bilateral lung involvement was the predominant pattern in both severe and critical patients, whereas the number of involved lobes in critical patients was more than that in severe patients (P = 0.024). Peripheral distribution was the predominant pattern in severe patients (40%), whereas more diffuse involvement of the lungs was observed in critical patients (83.30%). Ground‐glass opacities and consolidation were the main CT findings in both groups, and prevalence of consolidation was higher in critical relative to severe group (83.30%). Conclusion Compared with severe patients, those with critical H1N1 pneumonia were more likely to present with dyspnea at rest and decreased lymphocyte percentage. Chest CT showed that diffuse bilateral involvement and higher prevalence of consolidation are associated with critical outcomes.

Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases.

Objectives Extramedullary disease (EMD) is characterized by plasma cells outside of bone marrow in multiple myeloma (MM) patients, which results in an adverse prognosis. EMD treatment is yet challenging even in the era of novel drugs. Only limited data are available on pomalidomide-based therapy for EMD patients. The purpose of the current study was to assess the efficacy of pomalidomide-based therapy in EMD. Methods The current retrospective analysis of six patients assessed the utility of pomalidomide-based therapy in the treatment of EMD. Results The median age at diagnosis was 55 (47–70) years. A serological response was observed: 16% (n = 1) complete response (CR), 67% (n = 4) partial response (PR), and 16% (n = 1) progressive disease (PD). Extramedullary overall response rate (ORR) was 83% (n = 5), with 50% (n = 3) CR, 33% (n = 2) PR, and extramedullary progression in one patient. The median progression-free survival (PFS) was 5 months and the median overall survival (OS) was 8 months from diagnosis of EMD. Discussion and conclusion Pomalidomide-based therapy showed efficacy in these previously treated patients with EMD.

Background Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy showed remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). This phase 1 dose-escalation and expansion study developed C-CAR088, a novel second-generation humanized anti-BCMA CAR T-cell therapy, and assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM.Methods Patients received lymphodepletion with three doses of cyclophosphamide (300 mg/m2) and three doses of fludarabine (30 mg/m2) on days –5, –4, and –3, followed by an infusion of C-CAR088 on day 0. Doses of 1.0×106, 3.0×106, and 6.0×106 CAR T cells/kg (±20%) were tested in the dose-escalation cohorts and expansion cohorts. The primary endpoint was treatment safety, including the rate of treatment-emergent adverse events after cell infusion. Secondary endpoints were the overall response rate and progression-free survival. The exploratory endpoints were the quantification of C-CAR088 CAR T cells, selection of cytokines and chemokines in blood, and measurement of tumor BCMA expression.Results As of July 2, 2021, 31 patients had been infused with C-CAR088. Any grade cytokine release syndrome (CRS) occurred in 29 patients (93.5%), and grade 3 CRS occurred in 3 patients (9.7%). One patient from the high-dose group (4.5–6.0×106 CAR T cells/kg) developed grade 1 neurotoxicity. No dose-limiting toxicities were observed in any dose group, and all adverse events were reversible after proper management. The overall response, stringent complete response, complete response (CR), and very good partial response rates were 96.4%, 46.4%, 10.7%, and 32.1%, respectively. The CR rate in the medium-dose (3.0×106 CAR T cells/kg) and high-dose (4.5–6.0×106 CAR T cells/kg) groups was 54.5% and 71.4%, respectively. In the CR group, 15 (93.7%) patients achieved minimal residual disease (MRD) negativity (test sensitivity >1/10−5). All seven patients with double-hit or triple-hit multiple myeloma achieved MRD-negative CR.Conclusions The present study demonstrated that C-CAR088 had a good safety profile and high antitumor activity in patients with RRMM, constituting a promising treatment option for RRMM.Trial registration number NCT03815383, NCT03751293, NCT04295018, and NCT04322292.

Extramedullary disease (EMD) is characterized by plasma cells outside of bone marrow in multiple myeloma (MM) patients, which results in an adverse prognosis. The cornerstone of treatment consists of combination therapy including proteasome inhibitors, immunomodulatory agents, steroids, followed by consolidative autologous hematopoietic stem cell transplantation in eligible patients. This review summarized the recent advances in the treatment of EMD. Bortezomib based therapy showed efficacy and was recommended to treat EMD. Marizomib had advantages in the treatment of central nervous system-multiple myeloma (CNS-MM) because of its good central nervous system penetrability. Immunomodulatory drugs such as lenalidomide and pomalidomide have been reported to be effective. Isatuximab and selinexor were also active. Based on the treatment experience of EMD in our department, we summarized treatment approach for EMD. However, the benefits of patients with EMD from the new era of novel drugs were limited. Novel drugs combination, monoclonal antibody, molecular targeted therapy, cellular immunotherapy and autologous stem cell transplantation (ASCT) are under investigation. Therapeutic studies and clinical trials specifically target EMD should be conducted. Hopefully, these treatment options for EMD will be demonstrated efficacy in the future.

BackgroundInterleukin-17, the major proinflammatory cytokine secreted by Th17 cells, makes essential contribution to pathogenesis of severe asthma, while the detailed mechanisms, especially the involvement of microRNAs which are also important participants in asthma progression, remains largely unclear.MethodsIn this study, we established a house dust mite (HDM) extract-induced murine asthmatic models and the miRNA expression in the lung tissues of mice were profiled by miRNA microarray assay. The effect of miR-365-3p on IL-17-mediated inflammation was examined by qRT-PCR and immunoblotting analysis. The involvement of ARRB2 as target gene of miR-365-3p was verified by overexpression or RNA interference.ResultsHDM extract-induced asthmatic inflammation was proved to be IL17-mediated and miR-365-3p was screened out to be the only miRNA exclusively responsive to IL-17. miR-365-3p, whose expression was significantly downregulated upon IL-17 stimulation, was demonstrated to exert remarkable anti-inflammatory effect to decrease IL-17-provoked inflammatory cytokines (KC/IL-8 and IL-6) in both airway epithelial cells and macrophages of murine and human origins, verifying its universal antagonizing activity against IL-17-initiated inflammation across the two species. ARRB2 was characterized as the key target of miR-365-3p to negate IL-17-induced inflammatory cytokines.ConclusionTaken together, our data supported the notion that miR-365-3p, which was diminished by IL-17 in murine and human asthmatic pathogenesis, functioned as an essential negative mediator in IL-17-stimuated inflammatory response by targeting ARRB2, which would shed new light to the understanding and therapeutics thereof of asthmatic inflammation.

Colon cancer is one of the most common gastrointestinal tumors in the world. Currently, the commonly used methods such as radiotherapy, chemotherapy and drug treatments are often ineffective and have significant side effects. Here we developed a safe and efficient biomaterials based anti-tumor nanoplatform (M@NPs/miR365), which was formed with poly (citrate-peptide) (PCP), miRNA365 mimic and MC38 cancer cell membrane (M). PCP could efficiently deliver miR365 mimic into MC38 cancer cells, promote the apoptosis of MC38 tumor cells and regulate the expression of Bcl2 and Ki67 in vitro. Tumor cell membranes were prepared by a fast and convenient sonication method. This tumor cell membrane-coated drug delivery system M@NPs can effectively reduce macrophage uptake and increase the stability of NPs. And the MC38 tumor model mice experiment showed that M@NPs/miR365 via caudal vein injection effectively inhibit tumor development. Based on the immune escape and homologous targeting of cancer cells and efficient gene transfection ability of NPs, this “Trojan horse” like “Pseudotumor cell” carries the target gene miR365 mimic to the tumor site and realizes cancer therapy. Noteworthy, the drug delivery system has good biocompatibility. Thus, this safe drug delivery strategy mediated by cancer cell membrane and gene therapy may have a certain significance for reducing the gap between nanoplatform and tumor clinical treatment.

Objective: To investigate the effect of tubeimoside-1 on the phenotype of skin squamous cell carcinoma SCL-1 cells and possible mechanism of action. Methods: SCL-1 cells were divided into the control group and the treatment groups, including different doses (5, 10, 20 μg/mL) of tubeimoside-1 groups, si-NC group, si-circ_0000376 group, tubeimoside-1+ pcDNA group, and tubeimoside-1+pcDNA-circ_0000376 group. CCK-8 method was used to detect cell proliferation inhibition rate.Transwell was used to detect cell migration and invasion. Flow cytometry was used to detect cell apoptosis. Western blot was used to detect the protein expression of Ki-67, MMP-2, MMP-9, Bcl-2 and Bax. RT-qPCR method was used to detect the expression of circ_0000376 and miR-203. The dual luciferase reporter gene experiment was used to verify the regulatory relationship between circ_0000376 and miR-203. Results: Compared with the control group, the proliferation inhibition rate, apoptosis rate and the Bax protein expression of cells in the tubeimoside-1 group were significantly increased (F=772.61, 352.20, 277.56, all P

Abstract In this study, we investigated the expression profiles of Toll-like receptors(TLRs) in eutopic endometrium(EU) and ectopic endometrium(EC) and its implication in the inflammatory pathogenesis of adenomyosis. Thirty adenomyosis patients who underwent laparoscopy were recruited in this study. We tested the mRNA and protein expression of TLRs, and the mRNA expression of IL-6 and IL-8 in EU and EC of adenomyosis patients, and control endometrium without adenomyosis(CE). We found that the mRNA expression of IL-6 and IL-8 in EU was significantly higher than that in CE, and was the highest in EC (P

Objective This study aimed to investigate RhoA, RhoA-associated coiled-coil containing protein kinase (ROCK) 1, ROCK2, and Rho GTPase-activating protein 26 (ARHGAP26) expression in the eutopic endometrium (EU) and ectopic endometrium (EC), and examine their relationships with the clinical characteristics of adenomyosis. Methods Twenty patients with adenomyosis who underwent laparoscopy were recruited. Protein and mRNA expression of RhoA, ROCK1, ROCK2, and ARHGAP26 in EU and EC of patients with adenomyosis and in control endometrium without adenomyosis (CE) was detected. Results ROCK1, ROCK2, and RhoA mRNA expression in EU was significantly higher than that in CE, and was highest in EC. ARHGAP26 mRNA expression in EC and EU was significantly lower than that in CE. ROCK1, ROCK2, and RhoA protein expression in EC and EU was significantly higher than that in CE. ARHGAP26 protein expression in EC and EU was significantly lower than that in CE. ROCK1, ROCK2, and RhoA gene and protein expression was positively associated and ARHGAP26 was negatively associated with the severity of menorrhagia and menstrual capacity in adenomyosis. Conclusions RhoA, ROCK1, and ROCK2 expression is upregulated, and ARHGAP26 expression is downregulated in adenomyosis. The RhoA/ROCK-mediated signaling pathway is associated with dysmenorrhea and menstrual capacity in adenomyosis.

Background. Inflammation plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We evaluated the lncRNA and mRNA expression profile of peripheral blood mononuclear cells (PBMCs) from healthy nonsmokers, smokers without airflow limitation, and COPD patients. Methods. lncRNA and mRNA profiling of PBMCs from 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated lncRNAs was validated by qPCR. The lncRNA targets in dysregulated mRNAs were predicted and the GO enrichment was analyzed. The regulatory role of lncRNA ENST00000502883.1 on CXCL16 expression and consequently the effect on PBMC recruitment were investigated by siRNA knockdown and chemotaxis analysis. Results. We identified 158 differentially expressed lncRNAs in PBMCs from COPD subjects compared with smokers. The dysregulated expression of 5 selected lncRNAs NR_026891.1 (FLJ10038), ENST00000502883.1 (RP11-499E18.1), HIT000648516, XR_429541.1, and ENST00000597550.1 (CTD-2245F17.3), was validated. The GO enrichment showed that leukocyte migration, immune response, and apoptosis are the main enriched processes that previously reported to be involved in the pathogenesis of COPD. The regulatory role of ENST00000502883.1 on CXCL16 expression and consequently the effect on PBMC recruitment was confirmed. Conclusion. This study may provide clues for further studies targeting lncRNAs to control inflammation in COPD.

The objective of the present study was to investigate differences in the expression of apoptosis-related factors in the eutopic and ectopic endometrium (EuE/EE) in women with adenomyosis before and after laparoscopic bilateral uterine artery occlusion (LUAO). Ten patients with uterine adenomyosis who received LUAO were selected as the research subjects, from whom EuE and EE tissues were obtained before and after LUAO and detected for the expression of apoptosis-related molecules in EuE and EE by PT-PCR and Western blot, and changes in the mitochondrial structure by electron microscopy. Normal endometrial stromal cells (NESC), and EuE/EE stromal cells in women with adenomyosis were cultured in a 1% O2, 5% CO2 incubator to establish a physical anoxia state in an in vitro stromal cell model. The expression of apoptosis-related molecules was observed at 0, 6, 12, 24 and 48h of hypoxic. The results showed that the expression of apoptosis-related factors in EuE and EE were increased significantly after LUAO and under hypoxic conditions in vitro, suggesting that transient ischemia and hypoxia were involved in the apoptosis of adenomysis lesions, and that uterine artery occlusion could remove adenomyosis lesions on tissue/cell level by cytoreduction, thus reaching the goal of treating adenomyosis effectively.

MADS-box proteins, a well-conserved family of transcription factors in eukaryotic organisms, specifically regulate a wide range of cellular functions, including primary metabolism, cell cycle, and cell identity. However, little is known about roles of the MADS-box protein family in the fungal pathogen Sclerotinia sclerotiorum. In this research, the S. sclerotiorum MADS-box gene SsMADS was cloned; it encodes a protein that is highly similar to Mcm1 orthologs from Saccharomyces cerevisiae and other fungi, and includes a highly conserved DNA-binding domain. MADS is a member of the MADS box protein SRF (serum response factor) lineage. SsMADS function was investigated using RNA interference. Silenced strains were obtained using genetic transformation of the RNA interference vectors pS1-SsMADS and pSD-SsMADS. SsMADS expression levels in silenced strains were analyzed using RT-PCR. The results showed that SsMADS mRNA expression in these silenced strains was reduced to different degrees, and growth rate in these silenced strains was significantly decreased. Infecting tomato leaflets with silenced strains indicated that SsMADS was required for leaf pathogenesis in a susceptible host. Our results suggest that the MADS-box transcription factor SsMADS is involved in S. sclerotiorum growth and virulence.

Arsenic trioxide (As(2)O(3)) has shown remarkable efficacy for the treatment of multiple myeloma (MM). Histone deacetylases (HDAC) play an important role in the control of gene expression, and their dysregulation has been linked to myeloma. Especially, HDAC6, a unique cytoplasmic member of class II, which mainly functions as α-tubulin deacetylase and Hsp90 deacetylase, has become a target for drug development to treat cancer due to its major contribution in oncogenic cell transformation. However, the mechanisms of action for As(2)O(3) have not yet been defined. In this study, we investigated the effect of As(2)O(3) on proliferation and apoptosis in human myeloma cell line and primary myeloma cells, and then we studied that As(2)O(3) exerts antimyeloma effects by inhibiting activity in the α-tubulin and Hsp90 through western blot analysis and immunoprecipitation. We found that As(2)O(3) acts directly on MM cells at relatively low concentrations of 0.5~2.5 µM, which effects survival and apoptosis of MM cells. However, As(2)O(3) inhibited HDAC activity at the relatively high concentration and dose-dependent manner (great than 4 µM). Subsequently, we found that As(2)O(3) treatment in a dose- and time-dependent fashion markedly increased the level of acetylated α-tubulin and acetylated Hsp90, and inhibited the chaperone association with IKKα activities and increased degradation of IKKα. Importantly, the loss of IKKα-associated Hsp90 occurred prior to any detectable loss in the levels of IKKα, indicating a novel pathway by which As(2)O(3) down-regulates HDAC6 to destabilize IKKα protein via Hsp90 chaperone function. Furthermore, we observed the effect of As(2)O(3) on TNF-α-induced NF-κB signaling pathway was to significantly reduced phosphorylation of Ser-536 on NF-κB p65. Therefore, our studies provide an important insight into the molecular mechanism of anti-myeloma activity of As(2)O(3) in HDAC6-Hsp90-IKKα-NFκB signaling axis and the rationale for As(2)O(3) can be extended readily using all the HDAC associated diseases.

Advancements in animal models and cell culture techniques have been invaluable in the elucidation of the molecular mechanisms that regulate muscle atrophy. However, few studies have examined muscle atrophy in humans using modern experimental techniques. The purpose of this study was to examine changes in global gene transcription during immobilization-induced muscle atrophy in humans and then explore the effects of the most prominent transcriptional alterations on protein expression and function. Healthy men and women (N = 24) were subjected to two weeks of unilateral limb immobilization, with muscle biopsies obtained before, after 48 hours (48 H) and 14 days (14 D) of immobilization. Muscle cross sectional area (approximately 5%) and strength (10-20%) were significantly reduced in men and women (approximately 5% and 10-20%, respectively) after 14 D of immobilization. Micro-array analyses of total RNA extracted from biopsy samples at 48 H and 14 D uncovered 575 and 3,128 probes, respectively, which were significantly altered during immobilization. As a group, genes involved in mitochondrial bioenergetics and carbohydrate metabolism were predominant features at both 48 H and 14 D, with genes involved in protein synthesis and degradation significantly down-regulated and up-regulated, respectively, at 14 D of muscle atrophy. There was also a significant decrease in the protein content of mitochondrial cytochrome c oxidase, and the enzyme activity of cytochrome c oxidase and citrate synthase after 14 D of immobilization. Furthermore, protein ubiquitination was significantly increased at 48 H but not 14 D of immobilization. These results suggest that transcriptional and post-transcriptional suppression of mitochondrial processes is sustained throughout 14 D of immobilization, while protein ubiquitination plays an early but transient role in muscle atrophy following short-term immobilization in humans.