Digestive system manifestations and clinical significance of coronavirus disease 2019: A systematic literature review.

BACKGROUND AND AIM: A worldwide outbreak of coronavirus disease 2019 (COVID-19) has drawn global attention. Several reports have described the gastrointestinal (GI) manifestations in the infected patients. The systematic review was designed to highlight the gaps in our knowledge about the prevalence and clinical significance of GI symptoms in patients with COVID-19. METHODS: We searched PubMed database and Google articles published in both English and Chinese up to June 3, 2020, using search terms "clinical features," "2019 novel coronavirus," "2019-nCoV," "COVID-19," or "SARS-Cov-2." Observational studies, case reports, or letters describing the clinical features or observational studies regarding the detection and/or isolation of severe acute respiratory syndrome coronavirus 2 viruses in stools were included. RESULTS: A total of 22 publications were finally selected. It was reported that GI symptoms occurred in about 3-40.7% of patients. GI manifestations included nausea, diarrhea, anorexia, vomiting, abdominal pain, belching, abdominal distension, and GI hemorrhage. Diarrhea was the most common GI symptom. Infected patients had various degrees of liver dysfunction, and the severity of liver dysfunction was significantly associated with the severity of the disease. Therapy focusing on digestive system like liver supportive therapy or nutrition support or probiotics has been demonstrated to be effective interventions, which greatly improve prognosis. Fecal-oral transmission route is a potential risk for transmission. CONCLUSIONS: GI symptoms are common in COVID-19. Strengthening the recognition on abnormalities in digestive system of patients with COVID-19 is crucial for early identification and timely treatment, especially for those atypical patients. Hygiene protection and keeping the drainpipe free flowing are necessary for everyone.

A Modified Approach with Caval Transection for Supracardiac Total Anomalous Pulmonary Venous Connection: Comparison Between Conventional and Sutureless Surgery in 173 Patients.

The efficacy of primary sutureless repair for supracardiac total anomalous pulmonary venous connection (TAPVC) needs to be confirmed. This study aimed to compare the long-term outcomes between the conventional surgery and the sutureless technique with a modified approach in superior TAPVC. Between January 2008 and December 2018, 173 patients with supracardiac TAPVC underwent surgery either with the conventional procedure (n = 130) or the sutureless repair (n = 43). Multivariate analysis and competing-risk analysis were used to identify risk factors for early death and postoperative pulmonary venous obstruction (PVO), respectively. Among 173 patients who underwent repair of supracardiac TAPVC, 46 (28%) had preoperative PVO, and 22 (12.7%) had postoperative PVO. The sutureless group had a lower postoperative PVO rate compared with the conventional group (p = 0.027). The risk factors for death were age ≤ 28 days [odds ratio (OR), 11.56; 95% confidence interval (CI) 1.33-100.47, p = 0.015], weight ≤ 3 kg (OR 9.57; 95% CI 1.58-58.09, p = 0.009), emergency operation (OR 19.24; 95% CI 3.18-116.35, p = 0.002), cardiopulmonary bypass time (OR 2.16; 95% CI 1.36-3.43, p = 0.003), cross-clamp time (OR 1.73; 95% CI 1.20-2.50, p = 0.022), and duration of ventilation (OR 1.11; 95% CI 1.02-1.21, p = 0.027). Age ≤ 28 days [Hazard Ratio (HR) 1.92; 95% CI 1.92-11.02, p < 0.001] and preoperative PVO (HR 41.70; 95% CI 8.15-213.5, p < 0.001) were associated with postoperative PVO. The sutureless repair is a reliable technique for supracardiac TAPVC. Age ≤ 28 days is associated with 30-day mortality and postoperative PVO.

Prognostic nomogram based on immune scores for laryngeal squamous cell cancer.

PURPOSE: Immune scores have been used as a prognostic factor for various types of cancer. However, the association between immune scores and the prognosis of laryngeal squamous cell cancer (LSCC) has not yet been investigated. This study aimed to explore the prognostic significance of immune scores and construct a clinical nomogram to predict the survival of patients with LSCC. METHODS: The clinicopathological characteristics and immune scores of 102 patients with LSCC were obtained from TCGA database and a nomogram was developed. C-index and calibration curves were applied to assess the performance of the model. RESULTS: Patients with higher immune scores had significantly better overall survival (OS). The prognostic nomogram presented a good performance in survival prediction. CONCLUSIONS: High immune scores are correlated with improved OS in patients with LSCC. In addition, the nomogram developed for this study may assist clinicians in the prognostic evaluation of patients with LSCC.

Systematic evaluation of therapeutic effects of stem cell transplantation trials for heart diseases in China.

BACKGROUND: To systematically assess the quality of reports of clinical trials of stem cell for heart diseases published in Chinese. METHODS: The quality of reports was assessed according to the CONSORT statement and the Jadad score. The association between the CONSORT scores and the reported therapeutic effects was evaluated. RESULTS: A total of 36 randomized clinical trials were identified, and 1552 patients were included. The mean CONSORT score was 7.06 (SD = 2.99). The proportion of reports with a Jadad score of 3 was 8.33%. The improvement of left ventricular function, myocardial perfusion area, left ventricular diastolic diameter, and cardiac output decreased with the increase in the CONSORT score. CONCLUSIONS: The percentages of high-quality reports published in Chinese on stem cell therapy for heart diseases are low. Although stem cell transplantation seems promising for heart diseases, high-quality studies are needed to verify the conclusions．.

Identification of core biomarkers associated with pathogenesis and prognostic outcomes of laryngeal squamous-cell cancer using bioinformatics analysis.

PURPOSE: Despite advances in the treatment of laryngeal squamous-cell carcinoma (LSCC), the survival rate of LSCC remains poor. Thereby, it is urgent to identify novel diagnostic and prognostic biomarkers for LSCC. The study aimed to identify potential core genes associated with the pathogenesis and prognosis of LSCC. METHODS: Differentially expressed genes between LSCC and normal laryngeal tissue samples were screened by an integrated analysis of data from GEO and TCGA databases. Core genes related to the pathogenesis and prognosis of LSCC were identified by employing protein-protein interaction network and Cox proportional hazards model analyses. RESULTS: Ten hub genes (AURKA, AURKB, CDC45, KIF2C, NDC80, EXO1, TYMS, RAD51AP1, ITGA3, and UBE2T) that might be highly related to the pathogenesis of LSCC were identified. An eight-gene prognostic signature consisted of ZG16B, STATH, RTN4R, MSRA, CBX8, SLC5A1, EFNB1 and CNTFR was constructed with a good performance in predicting overall survivals. CONCLUSION: Our findings might shed some new light on the pathogenesis of LSCC and help identify new therapeutic targets of LSCC.

Comparison of the short-term and long-term outcomes of surgical treatment versus endoscopic treatment for early esophageal squamous cell neoplasia larger than 2 cm: a retrospective study.

BACKGROUND: NCCN Guidelines of esophageal cancer recommend that endoscopic therapy is considered "preferred" for patients with limited early-stage disease less than or equal to 2 cm. However, there is currently no definite evidence to support either endoscopic therapy or esophagectomy for early esophageal cancer larger than 2 cm. We aimed to explore the optimal treatment for this condition. METHODS: From January 2010 to June 2016, 116 patients with early esophageal neoplasia [high-grade dysplasia (HGD), lamina propria and muscularis mucosae (T1a) cancer, selected superficial submucosa (T1b) cancer without lymph node metastases] larger than 2 cm and treated either surgically or endoscopically were included. RESULTS: Endoscopic therapy was performed in 69 patients and esophagectomy in 47 patients, respectively. The median follow-up time was 43.8 months in the endoscopic cohort and 49.4 months in the surgical cohort. The overall survival was similar between the two cohorts (97.1% vs. 91.5%, P = 0.18). Survival without readmission for treatment-related complicates was also similar. Minor and severe procedure-related complications occurred more often in the surgical cohort than in the endoscopic cohort (63.8% vs. 43.5% and 8.5% vs. 0 respectively, P < 0.05 for both). Four patients in the endoscopic cohort had to undergo additional esophagectomy and were alive during follow-up. There were no procedure-related deaths in the endoscopic cohort, whereas two deaths occurred in the surgical cohort. Recurrence occurred in nine patients in the endoscopic group (13%): six with local recurrence, one with residual neoplasia and two with metachronous neoplasia. None of them died after repeated endoscopic treatments. CONCLUSIONS: Efficacy was similar between endoscopic therapy and esophagectomy in the treatment of early esophageal squamous cell neoplasia larger than 2 cm and endoscopic therapy was associated with fewer and manageable complications. We recommend endoscopic treatment should be preferred selected for early esophageal neoplasia larger than 2 cm.

The safety of catheter ablation for premature ventricular contractions in patients without structural heart disease.

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often symptomatic. Catheter ablation was usually indicated to eliminate symptoms in patients with PVCs-induced cardiomyopathy. Currently, PVCs-ablation is also applied for patients with PVCs and no structural heart diseases (SHD); however, the safety and efficacy of ablation in these patients remains unclear. METHODS: In this retrospective study, data from patients who underwent ablation for PVCs from January 2010 to December 2016 at our hospital was retrieved. Predictors of complications and acute procedural success were evaluated. RESULTS: A total of 1231 patients (mean age 47.8 ± 16.8 years, 59% female) were included. The overall complication rate was 2.7%, and the most common complication was hydropericardium. Two ablation-related mortalities occurred. One patient died of coronary artery injury during the procedure and the other died from infectious endocarditis. Location (left ventricle and epicardium) was the main predictor of complications, with right ventricular outflow tract (RVOT) predicting fewer complications. The acute procedural success rate was 94.1% in all patients. The main predictor of acute procedural success was RVOT origin, while an epicardial origin was a predictor of procedural failure. CONCLUSION: Locations of left ventricle and epicardium were predictors of procedural complications for patients with PVCs. Therefore, ablation is not recommended in these patients. For other origins of PVCs, particularly RVOT origin, ablation is a safety and effective treatment.

Red yeast rice induces less muscle fatigue symptom than simvastatin in dyslipidemic patients: a single center randomized pilot trial.

BACKGROUND: About 10-15% patients who take statins experience skeletal muscle problems. Red yeast rice has a good safety profile could provide a compromise therapeutic strategy. Therefore, the aim of this study was to evaluate the effects of red yeast rice, when compared to simvastatin, on the muscle fatigue symptom and the serum lipid level in dyslipidemic patients with low to moderate cardiovascular risk. METHODS: A total of 60 dyslipidemic patients with low to moderate cardiovascular risk were recruited and randomly assigned to receive either simvastatin (n = 33) or red yeast rice (n = 27) for 4 weeks. The muscle fatigue score, the physical activity, the serum lipid profile and the safety profile were then evaluated. RESULTS: At the end of study, the fatigue score was significantly increased in patients treated with simvastatin, whereas no significant change was observed in patients receiving red yeast rice. In addition, the physical activity level was significantly decreased in patients from simvastatin group when compared to those from red yeast rice group. Similar lipid-lowering effects were observed in two groups. The safety profile was not affected after the treatments. CONCLUSIONS: Among dyslipidemic patients with low to moderate cardiovascular risk, red yeast rice induced less fatigue side effect and exerted comparable lipid-lowering effects when compared to simvastatin in this pilot primary prevention study. TRIAL REGISTRATION: NCT01686451 .

Very early recurrence predicts long-term outcome in patients after atrial fibrillation catheter ablation: a prospective study.

BACKGROUND: Long-term recurrence (LR) is a tendency that re-occurs within 3 months after catheter ablation for atrial fibrillation (AF). Whether very early recurrence (VER) within 7 days of post ablation is a prognostic factor of LR or not is unclear. For this reason, present study sought to examine the relationship between VER and LR. METHODS: In this prospective analysis 378 consecutive patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between VER and LR was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operator characteristic (ROC) analysis. RESULTS: After a mean follow-up of 14.71 ± 8.58 months, 81 (65.90%) patients with VER experienced LR and were associated with lower event of free survival from LR (Log rank test, P < 0.001). Multivariate Cox regression analysis revealed that VER (HR = 7.02, 95% CI = 4.78-10.31; P < 0.001), left atrial enlargement (HR = 2.92, 95% CI = 1.88-4.54; P < 0.001), tendency in advanced age (HR = 1.50, 95% CI = 0.99-2.28; P = 0.054), and tendency in male (HR = 0.71, 95% CI = 0.50-1.01; P = 0.060) were independent predictors of LR. According to time-dependent ROC analysis, it was found that VER was more sensitive than common risk factors in predicting LR (0.74 vs 0.66, P < 0.001) and combination model further improved the C statistic for predicting LR (0.82 vs 0.66, P < 0.001). CONCLUSIONS: After a single procedure of catheter ablation, patients with VER were strongly associated with LR and combination of VER and common risk factors could further improve prediction of patients who were at high risk for LR.

Comparing Cerebralcare Granule and aspirin for neurological dysfunction in acute stroke in real-life practice.

BACKGROUND: Cerebralcare Granule (CG) is a polyherbal Chinese medicine that has been shown to have neuroprotective effects in experimental models of stroke. We compared the efficacy and safety of CG with aspirin in patients with acute stroke. METHODS: For this open-label, controlled trial, we recruited patients with angiographically confirmed strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 4-22 within 2 weeks of symptom onset; recruitment was performed at 55 sites in China. Patients received CG or aspirin. The primary efficacy end-point was neurological function. Analyses were done by intention to treat. Patients were measured for NIHSS, Montreal Cognitive Assessment, and Mini-Mental State Examination scores and Barthel index at baseline and at 4, 8, and 12 weeks after treatment. RESULTS: Between January 2013 and January 2014, we treated 1963 patients with CG and 1288 patients with aspirin. Baseline NIHSS, Mini-Mental State Examination, and Montreal Cognitive Assessment scores were comparable between the two groups. Patients in the CG group had a greater improvement than the aspirin group in terms of NIHSS (P < 0.01) and Barthel index at 4, 8, and 12 weeks. At 12 weeks, patients in the CG group had a greater improvement than the aspirin group in terms of Mini-Mental State Examination (P < 0.01) and Montreal Cognitive Assessment (P < 0.05). Adverse reactions were similar between the two groups. CONCLUSIONS: This large-scale, controlled trial indicated that CG may be a useful treatment in the management of post-stroke patients.

Applications of Nanoparticles for Anticancer Drug Delivery: A Review.

Biodegradable nanometer-sized particles have novel structural and physical properties that are attracting great interests from pharmaceuticals for the targeted delivery of anticancer drugs and imaging contrast agents. These smart nanoparticles are designed to ferry chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells. In this review, we describe currently clinically used chemotherapeutics in nanoparticle formulation and discuss the current status of nanoparticles developed as targeting delivery systems for anticancer drugs, with emphasis on formulations of micelles, liposome, polymeric nanoparticles, gold nanoparticle dendrimers, and bionanocapsules.

Evaluation of Hemostatic Effects of Carbonized Hair-Loaded Poly(L-Lactic) Acid Nanofabrics.

Carbonized human hair is used to stop bleeding in traditional Chinese medicine. The present study was aimed to prepare a novel nanofiber containing carbonized human hair and evaluate its hemostatic effect. Carbonized human hair-loaded poly(L-lactic) acid nanofiber was prepared by electrospinning. The hemostatic efficacies of dressings composed of either carbonized human hair, carbonized human hair-loaded poly(L-lactic) acid nanofiber, Yunnan White Drug power or poly(L-lactic) acid nanofiber were investigated in several swine arterial and venous bleeding models. Blood loss and bleeding time were measured. In vitro, carbonized human hair, carbonized human hair-loaded nanofiber and Yunnan White Drug Powder significantly shortened the clotting time in comparison with the nanofiber control group. The hemostatic effects of the carbonized human hair-load nanofiber on liver and spleen traumatic wounds were better than those of carbonized human hair and Yunnan White Drug Powder in terms of blood loss and bleeding time. Similar effects were observed in swine femoral artery wound model. In the swine femoral vein wound model, bleeding could not be stopped in the control animals. In the carbonized human hair group, Yunnan White Drug Powder group and carbonized human hair-load nanofiber group, bleeding was stopped in 83.3%, 83.3% and 100% of the animals, respectively. In conclusion, dressing using carbonized human hair-load nanofibers is effective in controlling severe, uncontrolled bleeding. This dressing may offer a cheap alternative to dressings composed of coagulation proteins.

The Inhibition of Escherichia coli Biofilm Formation by Gallium Nitrate-Modified Titanium.

Periprosthetic infections are notoriously difficult to treat due to biofilm formation. Previously, we reported that gallium-EDTA attached to PVC (polyvinyl chloride) surface could prevent bacterial colonization. Herein we examined the effect of this gallium-EDTA complex on Escherichia coli biofilm formation on titanium. It was clearly demonstrated that gallium nitrate significantly inhibited the growth and auto-aggregation of Escherichia coli. Furthermore, titanium with gallium-EDTA coating resisted bacterial colonization as indicated by crystal violet staining. When the chips were immersed in human serum and incubated at 37 °C, they demonstrated significant antimicrobial activity after more than 28 days of incubation. These findings indicate that gallium-EDTA coating of implants can result in a surface that can resist bacterial colonization. This technology holds great promise for the prevention and treatment of periprosthetic infections.

Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage.

Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH.

Exploration of the mechanisms by which 3,4-benzopyrene promotes angiotensin II-induced abdominal aortic aneurysm formation in mice.

OBJECTIVE: This study examined the influence of 3,4-benzopyrene (BaP), a compound found in cigarette smoke, on the formation of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) formation in mice and the underlying mechanisms. METHODS: C57/B6n mice were divided into four groups. The control group received a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal injection of medium-chain triglycerides. The Ang II/BaP group received a daily Ang II infusion (0.72 mg/kg) and a weekly intraperitoneal BaP injection (10 mg/kg, dissolved in medium-chain triglycerides). The BaP group received a weekly intraperitoneal BaP injection (10 mg/kg). After 5 weeks, abdominal aortic diameter was determined. Aortic tissues underwent hematoxylin and eosin, Masson, and immunochemistry staining for evaluation of vascular wall structure, collagen, macrophage infiltration, matrix metalloproteinases (MMPs), and apoptosis. RESULTS: The Ang II infusion and BaP injection induced AAAs in 41.67% of mice vs 25% in the Ang II group (P < .05). The average aortic diameter increased in the Ang II/BaP group compared with the Ang II group (1.40 ± 0.25 vs 1.2 ± 0.23 mm; P < .05). Average aortic muscular cell apoptosis was higher in the Ang II/BaP group (31% ± 12%) than in the Ang II (19% ± 5%; P < .05) or BaP groups (23% ± 4%; P < .05). Aortic macrophage infiltration and expression of MMP-2, MMP-9, MMP-12, and nuclear factor-κB increased (0.56 ± 0.12, 0.47 ± 0.13, 0.49 ± 0.14, 0.49 ± 0.11, and 0.42 ± 0.12, respectively) in the Ang II/BaP group compared with the Ang II group (0.27 ± 0.08, 0.25 ± 0.06, 0.24 ± 0.09, 0.24 ± 0.09, and 0.23 ± 0.06, respectively; P < .05 for all). CONCLUSIONS: BaP promotes Ang II-induced AAA formation in mice via elevating infiltration of macrophages, activating nuclear factor-κB, upregulating the expression of MMP-2, MMP-9, and MMP-12, and increasing the apoptosis of vascular muscle cells in its synergistic effect with Ang II in aortic wall.

Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in type 2 diabetes mellitus: an open-label, randomized controlled clinical trial.

BACKGROUND AIMS: The use of bone marrow mononuclear cells (BM-MNCs) has achieved great outcomes in clinical practice. We aim to evaluate the efficacy and safety of autologous BM-MNC infusion and hyperbaric oxygen therapy (HOT) in type 2 diabetes mellitus. METHODS: This single-center, randomized, open-label, controlled clinical trial with a factorial design included two phases. The patients received standard medical therapy in the run-in phase; in the treatment phase, patients with glycated hemoglobin of 7.5-9.5% were randomly assigned into four groups and underwent BM-MNC infusion along with HOT (BM-MNC+HOT group), BM-MNC infusion (BM-MNC group), HOT (HOT group) and standard medical therapy (control group), respectively. The area under the curve of C-peptide was recorded as a primary end point. Our research is registered at ClinicalTrials.gov (NCT00767260). RESULTS: A total of 80 patients completed the follow-up. At 12 months after treatment, the area under the curve of C-peptide (ng/mL per 180 min) of the BM-MNC+HOT group and the BM-MNC group were significantly improved (34.0% and 43.8% from the baseline, respectively). The changes were both significant compared with that in the control group, but no remarkable change was observed in the HOT group. Treatment-related adverse events were mild, including transient abdominal pain (n = 5) and punctual hemorrhage (n = 3). CONCLUSIONS: BM-MNC infusion for type 2 diabetes mellitus improves islet function and metabolic control, with mild adverse effects. HOT does not synergize with BM-MNC infusion.

Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms.

BACKGROUND AIMS: Minimal change nephrotic syndrome is the most frequent cause of nephrotic syndrome in childhood. Current treatment regimes, which include glucocorticoid hormones and immunosuppressive therapy, are effective and have fast response. However, because of the side effects, long treatment course, poor patient compliance and relapse, novel approaches for the disease are highly desired. METHODS: The adriamycin-induced nephrotic rat model was established. Rats were allocated to a model group, a prednisone group or mesenchymal stromal cell (MSC) group. Clinical parameters in each treatment group were determined at 2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin, p21 and monocyte chemoattractant protein-1 were determined through the use of quantitative real-time-polymerase chain reaction. Protein levels were determined by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were isolated and apoptotic rate after adriamycin with or without MSC treatment was analyzed by means of flow cytometry. RESULTS: MSC intervention improved renal function as assessed by urinary protein, blood creatinine and triglyceride levels. MSC intervention reduced adriamycin-induced renal tissue damage visualized by immunohistochemistry and light and electron microscopic analysis and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA and protein levels of synaptopodin and p21 in renal cortex were significantly increased. MSCs also restored synaptopodin mRNA and protein expression in isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal cortex and protein level in serum of the MSC treatment group were significantly decreased compared with that in the adriamycin-induced nephropathy model group. CONCLUSIONS: Our data indicate that MSCs could protect rats from adriamycin-induced minimal change nephrotic syndrome, and the protective effects of MSCs are mediated through multiple actions.

Mesenchymal stem/stromal cells induce the generation of novel IL-10-dependent regulatory dendritic cells by SOCS3 activation.

Suppression of immune response by mesenchymal stem/stromal cells (MSCs) is well documented. However, their regulatory effects on immune cells, especially regulatory dendritic cells, are not fully understood. We have identified a novel Sca-1(+)Lin(-)CD117(-) MSC population isolated from mouse embryonic fibroblasts (MEF) that suppressed lymphocyte proliferation in vitro. Moreover, the Sca-1(+)Lin(-)CD117(-) MEF-MSCs induced hematopoietic stem/progenitor cells to differentiate into novel regulatory dendritic cells (DCs) (Sca-1(+)Lin(-)CD117(-) MEF-MSC-induced DCs) when cocultured in the absence of exogenous cytokines. Small interfering RNA silencing showed that Sca-1(+)Lin(-)CD117(-) MEF-MSCs induced the generation of Sca-1(+)Lin(-)CD117(-) MEF-MSC-induced DCs via IL-10-activated SOCS3, whose expression was regulated by the JAK-STAT pathway. We observed a high degree of H3K4me3 modification mediated by MLL1 and a relatively low degree of H3K27me3 modification regulated by SUZ12 on the promoter of SOCS3 during SOCS3 activation. Importantly, infusion of Sca-1(+)CD117(-)Lin(-) MEF-MSCs suppressed the inflammatory response by increasing DCs with a regulatory phenotype. Thus, our results shed new light on the role of MSCs in modulating regulatory DC production and support the clinical application of MSCs to reduce the inflammatory response in numerous disease states.

Nanoparticle-dependent labeling of mesenchymal stem cell.

Mesenchymal stem cells (MSCs) are able to differentiate into osteoblasts, adipocytes and chondroblasts. They hold great promise for tissue regeneration and treatment of immune-related diseases. Efficient application of MSCs requires safe cell tracking to follow stem cell fate over time in the host environment after infusion. This review discusses the nanoparticle-mediated MSC labeling, with special emphasis on the influence of nanoparticles on MSC bioactivities. We emphasize the importance of establishing guidelines, protocols and standards for labeling of MSCs in future clinical trials, so that MSCs can become a therapeutic agent with a reliable safety.