Mesenchymal stem cells (MSCs) have been shown to exert immunomodulatory effects in both acute and chronic diseases. In acute inflammatory conditions like sepsis, cell therapy must be administered ...within hours of diagnosis, requiring "off-the-shelf" cryopreserved allogeneic cell products. However, their immunomodulatory potency, particularly in abilities to modulate innate immune cells, has not been well documented. Herein we compared the stabilities and functionalities of cultured versus thawed, donor-matched MSCs in modulating immune responses in vitro and in vivo. Cultured and thawed MSCs exhibited similar surface marker profiles and viabilities at 0 hr; however, thawed MSCs exhibited higher levels of apoptotic cells beyond 4 hrs. In vitro potency assays showed no significant difference between the abilities of both MSCs (donor-matched) to suppress proliferation of activated T cells, enhance phagocytosis of monocytes, and restore endothelial permeability after injury. Most importantly, in animals with polymicrobial sepsis, both MSCs significantly improved the phagocytic ability of peritoneal lavage cells, and reduced plasma levels of lactate and selected inflammatory cytokines without significant difference between groups. These results show comparable in vitro and in vivo immunomodulatory efficacy of thawed and fresh MSC products, providing further evidence for the utility of a cryopreserved MSC product for acute inflammatory diseases.
BACKGROUND:This is the first study to use meta-analysis as a scientific technique to provide an integrated analysis of the effectiveness of music intervention in cancer patients.
OBJECTIVES:The ...purpose of this study was, using the meta-analysis method, to present a summary of existing research and explore the effectiveness of music intervention in ameliorating anxiety, depression, pain, and fatigue in cancer patients.
METHODS:The present study collected quantitative study designs sought of music intervention for cancer patients published from 2002 to 2012. These studies were then cross-referenced using Medical Subject Headings for topics on music intervention and cancer patients. Outcome indicators were anxiety, depression, pain, and fatigue. The quality of the studies was evaluated using Cochrane Collaboration Guidelines. The effect size on outcome indicators used the formula devised by Hedges and Olkin (1985).
RESULTS:Results showed that music interventions were significantly effective in ameliorating anxiety (g = −0.553), depression (g = −0.510), pain (g = −0.656), and fatigue (g = −0.422) in cancer patients. Subgroup analyses revealed that age and who selected the music were major factors influencing the effect size on anxiety reduction.
CONCLUSIONS:Music interventions significantly ameliorate anxiety, depression, pain, and fatigue in cancer patients, especially adults. Music interventions were more effective in adults than in children or adolescents and more effective when patients, rather than researchers, chose the music.
IMPLICATIONS FOR PRACTICE:Our findings provide important information for future music-intervention planners to improve the design and processes that will benefit patients in such programs.
As activation of the coagulation system is both a consequence and contributor to acute lung injury (ALI), pulmonary coagulopathy has become a potential target for therapeutic intervention in ALI ...patients. We investigated the effects and possible mechanisms of endothelial cell (EC)-anchored tissue factor pathway inhibitor (TFPI) on lipopolysaccharide (LPS)-induced ALI in mice. To assess the effect of EC-anchored TFPI deletion on ALI indices, TFPI knockout (cKO) mice were generated. Mice were instilled by direct intratracheal injection LPS for the preparation of an ALI model. Evans blue dye (EBD) was injected intravenously 2 h prior to animal sacrifice (48 h post-LPS). Lungs were fixed for histopathology and the prepared tissue was homogenized or used to extract bronchoalveolar lavage fluid (BALF) or detect EBD concentration. TFPI knockdown mice with ALI were compared to wild-type (WT) mice with ALI to assess the effect of TFPI on endothelial barrier function and inflammation. TFPI deletion markedly exacerbated LPS histopathological changes in lung, and the LPS changes in protein, EBD extravasation, proinflammatory cytokines TNF-α, IL-1β, and IL-6 in BALF in lung. The number and infiltration of white blood cells (WBCs) from BALF and lung tissue of TFPI cKO mice with LPS-challenged ALI was increased compared to WT mice with LPS-challenged ALI. We also found further increased toll-like receptor 4 and nuclear factor kappa-light-chain-enhancer of activated B cells activation and additional expression of vascular cell adhesion molecule 1 and reduction of angiotensin converting enzyme 2 expression in TFPI cKO+LPS mice compared with WT+LPS mice. Endothelial-specific TFPI deficiency promoted LPS-induced pulmonary inflammation and endothelial barrier permeability possibly via toll-like receptor 4-mediated nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway activation.
Influenza A virus (IAV)-induced acute lung injury (ALI) is characterized by pronounced proinflammatory activation and respiratory lung dysfunction. In this study, we performed deep immune profiling ...on airway and circulating immune cells to examine the effect of immunomodulation and therapeutic outcomes of mesenchymal stem cells (MSCs) therapy in mice with IAV-induced ALI.
Animals were inoculated intranasally with H1N1 IAV, followed by intravenous administration of vehicle, or human clinical-grade, bone marrow-derived MSCs 24-h later, and monitored for six days to evaluate the survival. In another set of animals, bronchoalveolar lavage (BAL) fluid and whole blood were collected three days after infection for flow or mass cytometry (CyTOF) immune profiling analysis.
Immune cell population and phenotypic shifts in blood were mapped by CyTOF. Increases were observed in granulocytes and myeloid-derived cells in blood from vehicle-treated animals. While MSC treatment accentuated changes in these populations, naïve B, antibody-secreting B cells, and T cells were decreased in MSC-treated animals at day 3. Compared to sham animals, IAV infection induced a significant 5.5-fold increase in BAL total cell counts, including CD4
and CD8
T cells, CD19
B cells, CD11b + Ly6G + neutrophils, and CD11b + Ly6C + monocytes. MSC treatment significantly decreased BAL total cell counts in IAV-infected mice, specifically the number of infiltrating CD4
T cells and CD11b + Ly6G + neutrophils. In contrast, there were increases in CD8
T cells, B cells, and monocytes in the alveolar space in MSC-treated animals. Phenotypic immune cell profiling of blood and BAL revealed a significantly higher proportion of the monocyte population with the M2 phenotype (CD206) in MSC-treated animals; however, this failed to confer protective effects in the survival of infected mice or reduce viral titer in the lung. Further investigation revealed that MSCs were susceptible to IAV infection, leading to increased cell death and potentially affecting their efficacy.
These findings provided
evidence that MSCs promote the selective recruitment of immune cells to the site of infection during IAV infection, with reductions in proinflammatory phenotypes. However, MSCs offered no survival benefit in IAV-infected animals, possibly due to MSCs' H1N1 IAV susceptibility and subsequent cell death.
SETTING: During 2000-2006, a regional anti-tuberculosis drug resistance surveillance study was conducted in Shanghai, China.OBJECTIVE: To determine the prevalence, trends and risk factors for ...drug-resistant tuberculosis (TB) in Shanghai, China.DESIGN: A retrospective study
of all pulmonary TB patients reported in Shanghai during 2000-2006 was conducted.RESULTS: Of 8419 pulmonary TB patients, 16.6% had resistance to any first-line anti-tuberculosis drug and 4.0% had multidrug resistance (MDR). The percentage of TB patients with resistance to any first-line
anti-tuberculosis drug and MDR significantly increased during 2000-2003 (P = 0.01 and P < 0.01, respectively). After improvements in the TB control programme in 2004, the increasing trend in drug resistance was contained. Age 30-59 years, being an urban
migrant and residence in an urban area of Shanghai were independently associated with resistance to any first-line drug and MDR in new cases, while age 30-59 years and being an urban migrant were independently associated with resistance to any first-line drug and MDR in previously treated
cases.CONCLUSIONS: Drug-resistant TB and MDR-TB pose a challenge for TB control in Shanghai. Improved case management, including DOTS and appropriate treatment regimens, should be sustained to prevent further transmission and development of drug-resistant TB in this setting.
To evaluate the potential anticancer effects of 1175 FDA-approved drugs, cell viability screening was performed using 25 human cancer cell lines covering 14 human cancer types. Here, we focus on the ...action of paroxetine, which demonstrated greater toxicity toward human gastric adenocarcinoma cell-line AGS cells compared with the other FDA-approved drugs, exhibiting an IC50 value lower than 10 μM. Evaluation of the underlying novel mechanisms revealed that paroxetine can enhance DNA damage in gastric cancer cells and involves downregulation of Rad51, HR23B and ERCC1 expression and function, as well as nucleotide shortage. Enhancement of autophagy counteracted paroxetine-induced apoptosis but did not affect paroxetine-induced DNA damage. Paroxetine also enhanced ROS generation in AGS cells, but a ROS scavenger did not improve paroxetine-mediated DNA damage, apoptosis, or autophagy, suggesting ROS might play a minor role in paroxetine-induced cell toxicity. In contrast, paroxetine did not enhance DNA damage, apoptosis, or autophagy in another insensitive gastric adenocarcinoma cell-line MKN-45 cells. Interestingly, co-administration of paroxetine with conventional anticancer agents sensitized MKN-45 cells to these agents: co-treated cells showed increased apoptosis relative to MKN-45 cells treated with the anticancer agent alone. Unequivocally, these data suggest that for the first time that paroxetine triggers cytotoxicity and DNA damage in AGS cells at least partly by reducing the gene expression of Rad51, HR23B, and ERCC1. Our findings also suggest that paroxetine is a promising candidate anticancer agent and/or chemosensitizing agent for use in combination with other anticancer drugs in cancer therapy. The molecular mechanisms underlying the anticancer activity of co-treatment with paroxetine and chemotherapy appear to be complex and are worthy of further investigation.
The Proteasome (PSM) is a large multi-catalytic protease complex consisting of a 20S core particle and a 19S regulatory particle whose main function is to accept and degrade ubiquitinated substrates, ...are now considered as one of the potential regulators of tumor proliferation, and stemness maintenance. However, to date, studies on the relationship between PSM and hepatocellular carcinoma (HCC) are limited.
This study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with PSM. A series of experiments in vivo and in vitro were performed to explore the function of the 26S proteasome non-ATPase regulatory subunit 13 (PSMD13) in HCC.
HCC patients can be divided into two clusters. Cluster 1 (C1) patients having a significantly worse prognosis than Cluster (C2). Two subtypes had significant differences in proliferation-related signaling. In particular, the frequency of
mutation was significantly higher in C1 than in C2. In addition, PSM-associated genes were highly consistent with the expression of DNA repair-related signatures, suggesting a potential link between PSM and genomic instability. We also found that downregulation of PSMD13 expression significantly inhibited stemness of tumor cells and impaired the Epithelial mesenchymal transition (EMT) process. Finally, the correlation between the PSMD13 and Ki67 was found to be strong.
PSM is a valid predictor of prognosis and therapeutic response in patients with HCC disease. Furthermore, PSMD13 may be a potential therapeutic target.
Purpose: Heart rate variability (HRV) indices have been used as stress indicators. Rare studies investigated the associations of circadian rhythms of the HRV indices with the stress, mood, and sleep ...conditions in populations under stress. Methods: In total 257 female participants (203 shift workers and 54 non-shift workers) were included. All the participants completed a structured questionnaire to assess the stress, mood, and sleep conditions and performed 24-hour Holter electrocardiogram monitoring on the day away from shifts. Using epochs of 1-min or 5-min beat-to-beat intervals, the HRV indices (SDNN, RMSSD, LF, HF, LF/HF, and LFnu, SD1, SD2, SD1/SD2) were plotted as a function of time and fitted into cosine periodic curves, respectively. Three mathematical parameters based on the cosine periodic curves were extracted, MESOR (M, overall averages of the cosine curve), amplitude (A, amplitude of the peak of the cosine curve), and acrophase (9, latency to the peak) to quantify the circadian rhythms of the HRV indices. Multivariable linear regression models were used to reveal the associations of these parameters with the clinical assessments of stress, mood, or sleep conditions, as well as with the 24-h averages of the HRV indices. Results: The parameters M and A of SDNN, RMSSD, LF, and HF, and 9 of LF/HF and LFnu significantly differ between shift and non-shift workers. The parameter 9 of LF/HF positively correlates with the severity of stress and anxiety. The parameter A of LF/HF and LFnu also positively correlates with daytime sleepiness and sleep fragmentation. In addition, the parameters M and A instead of 9 of SDNN, RMSSD, LF, LF/HF, and LFnu significantly correlate with the 24-h averages of HRV indices. Conclusion: The circadian rhythms of the HRV indices over 24 hours can, to some extent, predict the severity of stress, emotion and sleep conditions in female populations under stress. Keywords: circadian rhythms, HRV indices, mental health, stress, sleepiness, fatigue, sleep fragmentation
The fundamental principles and assumptions underlying an FEM model are described and this model has been used to predict the final dimensions of shaped components produced by hot isostatically ...pressing (HIPping) Ti–6Al–4V powder. A CAD module (solidworks) has been used for dimensional calibration, tooling design and engineering drawings. A relatively simple small casing component has been produced and the dimensions compared with those predicted from the modelling. It has been shown that there is agreement within about 2% between the achieved geometries and the predictions for this axial-symmetric cylinder body. The physical bases for some of the local discrepancies are discussed and future developments required for improved modelling are outlined.
Ta(20nm)/NiFe(5nm)/FeMn(20nm) films were deposited on glass substrates by rotational deposition at room temperature. A significant enhancement in the exchange bias field (Heb) associated with very ...low coercivity (Hc) was achieved for the samples prepared at rotational speed (Rrpm) of 1rpm. The Heb and Hc of the samples with Rrpm=1rpm were approximately double and smaller than half of those deposited by conventional continuous sputtering, respectively. Structural studies reveal that the rotational deposition not only improves the crystallization of FeMn but also facilitates the development of (111) texture through a preferred Ta(200) orientation. The sputtering powers of the constituent layers: WTa, WNiFe and WFeMn significantly affected the magnetic properties. Remarkable exchange bias properties, such as Heb of 26.67kA/m and Hc of 1.99kA/m were achieved at Rrpm=1rpm, WTa=40W, WNiFe=70W and WFeMn=140W. The Heb value obtained with the Ta/NiFe/FeMn films is comparable to that with the commercialized NiFe/IrMn system with a similar layered structure and it is more than 3 times larger than that of the sample deposited with fixed substrate in this study. The intensity of the FeMn(111) peak and the Scherrer coherent length are proportional to the Heb, indicating that the exchange bias behavior of the sample was dominated by the stability of the antiferromagnetic spin structure. The rotational deposition method proposed in this study favors practical applications in terms of both production cost and performance of spintronic devices.
•Rotational deposition•Enhanced exchange bias field•No post-annealing under H field
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