Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review.

BACKGROUND: Mesenchymal stem cells (MSCs) have been reported to possess immune regulatory effects in innate and adaptive immune reactions. MSCs can mediate intercellular communications by releasing extracellular vesicles (EVs), which deliver functional molecules to targeted cells. MSC derived EVs (MSC-EVs) confer altering effects on many immune cells, including T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages. A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases. This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases. AIM: To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases. METHODS: Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language. The keywords, such as "MSCs," "EVs," "exosome," "autoimmunity," "tumor immunity," and "transplantation immunity," and Boolean operator "AND" and "NOT" coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases. Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded. RESULTS: A total of 96 articles were chosen for final reference lists. After analyzing those publications, we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells, like T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages, to regulate immune responses in innate immunity and adaptive immunity. Many validated EVs-delivered molecules have been identified as key biomarkers, such as proteins, lipids, and nucleotides. Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease. CONCLUSION: MSC-EVs play an equally important part in the differentiation, activation, and proliferation of immune cells, and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.

Mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles: Potential roles in rheumatic diseases.

BACKGROUND: Mesenchymal stem cells (MSCs) have been widely investigated in rheumatic disease due to their immunomodulatory and regenerative properties. Recently, mounting studies have implicated the therapeutic potency of MSCs mostly due to the bioactive factors they produce. Extracellular vesicles (EVs) derived from MSCs have been identified as a promising cell-free therapy due to low immunogenicity. Rheumatic disease, primarily including rheumatoid arthritis and osteoarthritis, is a group of diseases in which immune dysregulation and chronic progressive inflammation lead to irreversible joint damage. Targeting MSCs and MSC-derived EVs may be a more effective and promising therapeutic strategy for rheumatic diseases. AIM: To evaluate the potential therapeutic effectiveness of MSCs and EVs generated from MSCs in rheumatic diseases. METHODS: PubMed was searched for the relevant literature using corresponding search terms alone or in combination. Papers published in English language from January 1999 to February 2020 were considered. Preliminary screening of papers concerning analysis of "immunomodulatory function" or "regenerative function" by scrutinizing the titles and abstracts of the literature, excluded the papers not related to the subject of the article. Some other related studies were obtained by manually retrieving the reference lists of papers that comply with the selection criteria, and these studies were screened to meet the final selection and exclusion criteria. RESULTS: Eighty-six papers were ultimately selected for analysis. After analysis of the literature, it was found that both MSCs and EVs generated from MSCs have great potential in multiple rheumatic diseases, such as rheumatoid arthritis and osteoarthritis, in repair and regeneration of tissues, inhibition of inflammatory response, and regulation of body immunity via promoting chondrogenesis, regulating innate and adaptive immune cells, and regulating the secretion of inflammatory factors. But EVs from MSCs exhibit much more advantages over MSCs, which may represent another promising cell-free restorative strategy. Targeting MSCs and MSC-derived EVs may be a more efficient treatment for patients with rheumatic diseases. CONCLUSION: The enormous potential of MSCs and EVs from MSCs in immunomodulation and tissue regeneration offers a new idea for the treatment of rheumatism. However, more in-depth exploration is needed before their clinical application.

Lactobacillus paracasei modulates LPS-induced inflammatory cytokine release by monocyte-macrophages via the up-regulation of negative regulators of NF-kappaB signaling in a TLR2-dependent manner.

The application of the probiotic lactobacillus is suggested in the treatment of some inflammatory diseases of intestines due to its potential ability to attenuate inflammation. However, the mechanism is not completely understood. In PBMCs, Lactobacillus paracasei (L. Paracasei) down-regulated the LPS-induced production of TNF-α and IL-6. Using a macrophage-like differentiated THP-1 cell line induced by PMA, we investigated the effect of L. paracasei on the production of pro-inflammatory cytokines by monocyte-macrophages. Treatment of the differentiated THP-1 cells with L. paracasei either concurrently with or before LPS challenge attenuated the LPS-induced secretion of TNF-α and IL-1ß. This effect was due to a decrease in IκB phosphorylation and NF-κB nuclear translocation. Furthermore, treatment of the differentiated THP-1 cells with L. paracasei induced the expression of negative regulators of the NF-κB signaling pathway, including the deubiquitinating enzyme A20, suppressor of cytokine signaling (SOCS) 1, SOCS3, and IL-1 receptor-associated kinase (IRAK) 3. Pretreatment with an IRAK4 inhibitor suppressed the L. paracasei-induced expression of these negative regulators and further increased the LPS-mediated expressions of TNF-α and IL-1ß. Moreover, treatment with an antibody against Toll-like receptor (TLR) 2 reversed the effect of L. paracasei on inducing negative regulators and inhibiting TNF-α and IL-1ß productions. Our findings suggest that L. paracasei inhibits the production of pro-inflammatory cytokines by monocyte-macrophages via the induction of negative regulators of the NF-κB signaling pathway in a TLR2-IRAK4-dependent manner.

Associations between CD24 gene polymorphisms and inflammatory bowel disease: A meta-analysis.

AIM: To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The PubMed, Web of Science and Cochrane Library databases were searched (up to May 30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis", "IBD", "CD" or "UC"; and "polymorphism", "mutation" or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed. Stata SE12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T (rs8734) and TG1527del (rs3838646), in the CD24 gene were assessed. RESULTS: A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD (all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170T polymorphism was associated with an increased risk of UC in a dominant model (OR = 1.79, 95%CI: 1.15-2.77, P = 0.009) and an additive model (OR = 1.87, 95%CI: 1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570del polymorphism was significantly associated with CD in the additive model (OR = 1.24, 95%CI: 1.01-1.52, P = 0.037). CONCLUSION: Our findings provide evidence that the CD24 C170T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527del polymorphism might be associated with the risk of CD.

[Identification and conservation assessment of suitable habitats for Tibetan antelope in the alpine desert, Qinghai-Tibet Plateau].

As a flagship and one of most endangered ungulates in the alpine desert of Qinghai-Tibet Plateau, the habitat conservation of Tibetan antelope (Pantholops hodgsonii) is vital to sustain its long-term population existence. In consideration of key habitat factors of the Tibetan antelope (i.e., food, topography and water source) as well as human interference factors like roads and settlements, the habitat suitability was modeled, and potential and valid suitable habitats were identified for Tibetan antelope in the alpine desert, Qinghai-Tibet Plateau. Furthermore, the conservation proportion index and conservation efficacy index were developed to facilitate the conservation assessment of three national reserves (i.e., Altun Mountain, Kekexili and Qiangtang) and their associated functional zones in the study area. The results showed that potential and valid area of suitable habitat across overall study area were 2.84 x 10(5) and 2.08 x 10(5) km2 respectively, with 16.1% of suitable habitat loss by human disturbance. At reserve level, the potential suitable habitats of Altun Mountain, Kekexili and Qiangtang were 2.01 x 10(4), 3.13 x 104 and 1.26 x 10(5) km2, which however decreased by 12.9%, 10.2% and 21.1% human disturbance respectively, indicating a prominent habitat fragmentation especially in Qiangtang National Nature Reserve (NNR). Although three NNRs had captured nearly 2/3 of the potential/valid suitable habitats with favorable conservation efficacy, there were still obvious conservation gaps outside the existing reserve network. At the functional zone level, buffer and experimental zones also showed significant conservation proportion and efficacy besides the core zone. Our research highlighted the necessity to optimize the existing re serve system by filling the conservation gaps, restructuring the functional zones and safeguarding the potential refuge habitats for those endangered ungulates in face of climate change.

[Meta-analysis of the efficacy and safety of telaprevir combined with peginterferon alfa plus ribavirin in patients with chronic hepatitis C].

OBJECTIVE: To evaluate the efficacy and safety of telaprevir combined with peginterferon alfa (Peg-IFNa) plus ribavirin (RBV) (collectively, TPR therapy) in patients with chronic hepatitis C (CHC) using a meta-analysis approach. METHODS: The Pubmed literature database was searched for randomized controlled trials of TRP therapy in CHC patients published between 2009 and 2011. The following outcome data was extracted for meta-analysis of efficacy: sustained virological response (SVR), defined as serum HCV RNA of less than 1000 copies/ml at end-of-treatment (week 24); rapid virological response (RVR), defined as serum HCV RNA of less than 1000 copies/ml at treatment week 4; recurrence, defined as serum HCV RNA of less than 1000 copies/mL at end-of-treatment and more than 1000 copies/ml at follow-up (week 24 after treatment completion). The pooled odds ratio (OR) or relative risk (RR) were calculated, with 95% confidence interval (CI). Heterogeneity was assessed by the Chi-squared test based on the Q statistic. RESULTS: Six studies of TPR triple therapy, representing a total of 2677 CHC patients, were included in the meta-analysis. Among the 1850 patients who received TPR, 56.3% (n = 1041) achieved RVR, 66.8% (n = 1235) achieved SVR, and 12.1% (n = 176/1460) experienced recurrence. Among the 827 patients who received PR double-therapy, 7.0% (n = 58) achieved RVR, 35.8% (n = 296) achieved SVR, and 32.3% (n = 145/449) experienced recurrence. The TRP group had significantly higher rates of RVR (OR = 29.83, 95% CI: 16.16 to 55.05) and SVR (OR = 3.97, 95% CI: 2.58 to 6.11) than the PR group (both P less than 0.01), and significantly lower rate of recurrence (RR = 0.36, 95% CI: 0.24 to 0.56, P less than 0.01). CONCLUSION: The therapeutic effect of research group is better than that of control group, suggesting that ornithine aspartate combined with naloxone treatment in hepatic encephalopathy is worthy of promoting.

An investigation of oxidative DNA damage in pharmacy technicians exposed to antineoplastic drugs in two Chinese hospitals using the urinary 8-OHdG assay / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate oxidative DNA damage in pharmacy technicians preparing antineoplastic drugs at the PIVAS (Pharmacy Intravenous Admixture Service) in two Chinese hospitals.</p><p><b>METHODS</b>Urinary 8-OHdG served as a biomarker. 5-Fluorouracil (5-FU) concentrations in air, masks and gloves were determined. The spill exposure of each PIVAS technician to antineoplastic drugs was investigated. Eighty subjects were divided into exposed group I, II, and control group I, II.</p><p><b>RESULTS</b>5-FU concentration ratios for gloves and masks in exposed group I were significantly higher than those in exposed group II (P<0.05 or P<0.01). The average urinary 8-OHdG concentrations in exposed group I, control group I, exposed group II, and control group II were 14.69±0.93, 10.68±1.07, 10.57±0.55, and 11.96±0.73 ng/mg Cr, respectively. Urinary 8-OHdG concentration in exposed group I was significantly higher than that in control group I or that in exposed group II (P<0.01). There was a significant correlation between urinary 8-OHdG concentrations and spill frequencies per technician (P<0.01).</p><p><b>CONCLUSION</b>There was detectable oxidative DNA damage in PIVAS technicians exposed to antineoplastic drugs. This oxidative DNA damage may be associated with their spill exposure experience and contamination of their personal protective equipment.</p>

[Randomized controlled study on acupuncture treatment for chronic fatigue syndrome].

OBJECTIVE: To observe the therapeutic effect of acpuncture treatment for chronic fatigue syndrome (CFS). METHODS: Nighty cases of CFS were randomly divided into an observation group and a control group, 45 cases in each group. The observation group was treated with acupunture at Renying (ST 9), Fengfu (GV 16), Baihui (GV 20); the control group was treated with 250 mL 5% Glucose injectio combined with 20 mL Shenmai injectio. Fatigue Scale (FS) was used to compare the scores between the two groups after treatment. RESULTS: The total scores in the observation group were 9.37 +/- 2.33 and 5.41 +/- 1.96 before and after treatment respectively, and in the control group, they were 9.08 +/- 2.27 and 7.34 +/- 2.03 respectively. FS brainwork integral, physical fatigue integral, and total integral all decreased after treatment in two groups (all P < 0.001), and it decreased much more obviously in the observation group (P < 0.05, P < 0.01). CONCLUSION: Both of the acpuncture treatment and Shenmai injectio are able to decrease fatigue scale score, improve the fatigue symptoms of CFS patients, and the effect of acupucture treatment is obviously superior to that of Shenmai injectio.

XRCC1 polymorphisms and risk of colorectal cancer: a meta-analysis.

PURPOSE: Previous studies investigating the association between X-ray repair cross-complementation group 1 (XRCC1) polymorphisms and colorectal cancer (CRC) risk has provided inconsistent results. The aim of our study was to clarify the effects of XRCC1variants on CRC risk. MATERIALS AND METHODS: We conducted searches of the published literature in PubMed, Embase, and CBM databases up to July 6, 2009. Meta-analysis was performed by critically reviewing 14 studies with a total of 2,776 CRC cases and 4,402 controls on Arg399Gln polymorphism, four studies with a total of 931 CRC cases and 1,547 controls on Arg280His polymorphism, and nine studies with a total of 1,709 CRC cases and 3,233 controls on Arg194Trp polymorphism, respectively. Statistical analysis was performed with the software programs Review Manager (version 5.0.10) and STATA (version 9.2). RESULTS: No significant association between Arg399Gln polymorphism and CRC risk was observed in both total population analyses and subgroup analyses based on ethnicity (OR(Co-dominant model) = 1.04, 95% CI 0.74-1.45, P (OR) = 0.82; OR(Dominant model) = 1.02, 95% CI 0.80-1.30, P (OR) = 0.88; OR (Recessive model) = 1.04, 95% CI 0.81-1.34, P (OR) = 0.78). Arg280His polymorphism also had no significant association with CRC risk (OR(Co-dominant model) = 0.85, 95% CI 0.32-2.31, P (OR) = 0.76; OR(Dominant model) = 1.11, 95% CI 0.87-1.40, P (OR) = 0.40; OR(Recessive model) = 0.85, 95% CI 0.32-2.31, P (OR) = 0.75). Besides, there was also no evidence of association between Arg194Trp polymorphism and CRC risk (OR(Co-dominant model) = 1.43, 95% CI 0.83-2.48, P (OR) = 0.20; OR(Dominant model) = 1.14, 95% CI 0.87-1.51, P (OR) = 0.34; OR(Recessive model) = 1.32, 95% CI 0.82-2.13, P (OR) = 0.25). CONCLUSIONS: No association is found between the polymorphisms in XRCC1 (Arg399Gln, Arg280His, and Arg194Trp) and risk of colorectal cancer.