Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study.

Introduction: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. Methods: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. Results: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = -0.212, p = 0.010) and in the subgroup with higher positive scores (r = -0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. Discussion: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.

Association of Attenuated Niacin Response With Inflammatory Imbalance and Prediction of Conversion to Psychosis From Clinical High-risk Stage.

Objective: Attenuated niacin responses and changes in cytokine levels have been reported in schizophrenia. However, prior studies have typically focused on schizophrenia, and little is known about the association between niacin response and inflammatory imbalance in clinically high-risk psychosis (CHR). This study aimed to assess the niacin response to inflammatory imbalance for association with conversion to psychosis within 2 years.Methods: A prospective case-control study was performed to assess the niacin response and interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels in 60 CHR individuals and 60 age- and sex-matched healthy controls (HC) from May 2019 to December 2021. Participants with CHR were identified using the Structured Interview for Prodromal Syndromes. The niacin-induced responses were measured using laser Doppler flowmetry. From the dose-response curves, the log-transferred concentration of methylnicotinate required to elicit a half-maximal blood flow response (LogEC50) and maximal minus minimal blood flow response (Span) values were calculated for each subject. Serum cytokine levels were measured using enzyme-linked immunosorbent assay. Individuals with CHR were then divided into converters (CHR-C, n = 15) and non-converters (CHR-NC, n = 45) to psychosis based on their 2-year follow-up clinical status.Results: The CHR group exhibited significantly higher LogEC50 (t = 3.650, P < .001) and Span (t = 2.657, P = .009) values than the HC group. The CHR-C group exhibited a significantly shorter Span (t = 4.027, P < .001) than the CHR-NC group. The LogEC50 showed a trend toward significance (t = 1.875, P = .066). None of the cytokine levels were significant. The conversion outcome can therefore be predicted by applying LogEC50 (P = .049) and Span (P < .001). The regression model with variables of LogEC50, Span, family history, and scores of positive symptoms showed good discrimination of subsequent conversion to psychosis and achieved a classification accuracy of 91.7%. The decreased LogEC50 in the CHR-C group was significantly correlated with the increased IL-1ß/IL-10 ratio (Spearman ρ = -0.600, P = .018), but this correlation was nonsignificant in the CHR-NC group.Conclusions: Our findings indicate a significant association between niacin response and psychosis conversion outcomes in individuals with CHR. Compared with peripheral inflammatory cytokines, the niacin response can better predict conversion, although there may be an intersection between the two in biological mechanisms.

A review of different breast reconstruction methods.

Breast reconstruction is necessary for the comprehensive treatment of breast cancer. For successful breast reconstruction, the timing of surgery and the surgical methods used are vital. The methods of breast reconstruction can be divided into implant-based breast reconstruction (IBBR) and autologous breast reconstruction (ABR). With the development of acellular dermal matrix (ADM), IBBR has become more common in clinical practice. However, the choice for the position in which the implant should be placed (prepectoral or subpectoral) and the use of ADM is currently controversial. We summarized the differences in indications, complications, advantages, disadvantages, and prognosis between IBBR and ABR. We also compared the indications and complications of different flaps in ABR and found that the LD (latissimus dorsi) flap is suitable for Asian women who have a low body mass index (BMI) and a low incidence of obesity, while the DIEP (deep inferior epigastric perforator) flap can be used in patients with severe breast ptosis. In conclusion, immediate breast reconstruction with an implant or expander is the primary method, as it causes lesser scarring and requires a shorter time compared to ABR. However, for patients with severe breast ptosis or reluctant to receive an implant, ABR can be performed for a satisfying cosmetic result. Indications and complications of different flaps in ABR are also inconsistent. Surgeons should make surgical plans based on the preferences and conditions of each patient. In the future, breast reconstruction methods need to be further refined, and minimally invasive and personalized approaches need to be implemented to provide more benefits to patients.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis.

INTRODUCTION: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). METHODS: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. RESULTS: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1ß (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. DISCUSSION: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Inhomogeneous Microstructure Evolution of 6061 Aluminum Alloyat High Rotating Speed Submerged Friction Stir Processing.

An inhomogeneous microstructure induced by high rotating speed submerged friction stir processing (HRS-SFSP) on 6061 aluminum alloy was researched in detail.The microstructures of the aluminum alloy processing zone were characterized by electron backscattered diffraction (EBSD) and transmission electron microscope (TEM) qualitatively and quantitatively.The results show that the recrystallization proportion in the inhomogeneous structure of the processing zone is 14.3%, 37.8% and 35.9%, respectively. Different degrees of grain deformation can affect the dislocation and lead to the formation of a plastic-elastic interface. At the same time, the second-phase particles in the processing zone were inhomogeneity and relatively, which further promotes the plastic-elastic interface effect. The plastic-elastic interface can significantly improve the strength of aluminum alloy, whileat the same time, rely on recrystallized grains to provide enough plasticity. When the rotation speed was 3600 r/min, the strength and ductility of the aluminum alloy after HRS-SFSP were increased by 48.7% and 10.2% respectively compared with that of BM. In all, the plastic-elastic interface can be formed by using high rotating speed submerged friction stir processing, and the strength-ductility synergy of aluminum alloy can be realized at the plastic-elastic interface.

Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk.

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1ß, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.

Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: A prospective cohort study.

Previous studies have revealed that the imbalance between Th1 cytokines and Th2 cytokines plays a role in disturbance of cellular responses in the brain during psychosis. Cross-sectional studies have implied that inflammatory cytokine changes emerge in early psychosis, even at the at-risk stage. This study aimed to test the hypothesis that inflammatory imbalance in clinical high-risk (CHR) individuals is associated with an increased risk of future psychosis. A prospective case-control study was performed to assess the Th1(interleukin (IL)-1ß)/Th2(IL-6) balance in 84 CHR individuals and 65 age- and sex-matched healthy controls (HC). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay at baseline and 1-year after the completion of the clinical assessment. Sixteen (19.0%) CHR participants converted to full psychosis during the 1-year follow-up period. At baseline, serum IL-1ß level was significantly lower in the CHR-converter group - resulting in decreased IL-1ß/IL-6 ratios - compared to those of the CHR-non-converter and HC groups. At the 1-year follow-up, IL-1ß level had decreased, and IL-1ß/IL-6 ratios had decreased in the CHR-non-converter group, such that these were comparable to values in the CHR-converter at this time point. Analysis of the changes in IL-1ß/IL-6 ratio between the baseline and 1-year follow-up measurements identified different trajectories in the CHR-converter and CHR-non-converter groups. Our findings demonstrate that a specific pattern of Th1/Th2 imbalance (decreased IL-1ß/IL-6 ratios with lower serum IL-1ß level) is associated with an increased risk of developing psychosis. Such specific pattern has potential for predicting conversion outcomes and selecting a distinct subgroup of CHR with immune-imbalanced-phenotype, that relevance in precise prevention.

RUNX1 overexpression triggers TGF-ß signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest.

p15INK4b (cyclin-dependent kinase inhibitor 2B, CDKN2B, p15), a cyclin-dependent kinase inhibitor (CKI) belonging to the INK4 family, plays an important role in hematopoiesis. Its expression level was positively related to the blockage effects of RUNX1b at the early stage. Experiments using human embryonic stem cell (hESC) lines with inducible p15 expression suggested that p15 overexpression can significantly decrease the proportion of KDR+ cells in S and G2-M stages 4 days after induction from day 0. Moreover, p15 overexpression from the early stage can decrease production of CD34highCD43- cells and their derivative populations, but not CD34lowCD43- cells. These effects were weakened if induction was delayed and disappeared if induction started after day 6. All these effects were counteracted by inhibition of TGF-ß signaling. TGF-ß1 stimulation elicited similar effects as p15 overexpression. RUNX1 overexpression and activation of the TGF-ß signaling pathway upregulate the expression of p15, which is partially responsible for blockade of hematopoiesis and relevant to a change in the cell cycle status. However, it is possible that other mechanisms are involved in the regulation of hematopoiesis.

Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells.

The generation of blood cells in a significant amount for clinical uses is still challenging. Human pluripotent stem cells-derived hemopoietic cells (hPSC-HCs) are a promising cell source to generate blood cells. Previously, it has been shown that the attached substrates are crucial in the maintenance or differentiation of hPSCs. In this study, a new family of artificial extracellular matrix (ECM) called colloidal self-assembled patterns (cSAPs: #1-#5) was used for the expansion of mouse and human PSCs. The optimized cSAP (i.e., #4 and #5) was selected for subsequent hemopoietic differentiation of human embryonic stem cells (hESCs). Results showed that the hematopoietic potential of hESCs was enhanced approx 3-4 folds on cSAP #5 compared to the flat control. The cell population of hematopoietic progenitors (i.e., CD34+CD43+ cells) and erythroid progenitors (i.e., CD71+GPA+ cells) were enhanced 4 folds at day 8 and 3 folds at day 14. RNA sequencing analysis of cSAP-derived hESCs showed that there were 300 genes up-regulated and 627 genes down-regulated compared to the flat control. The enriched signaling pathways, including up-regulation (i.e., Toll-like receptor, HIF-1a, and Notch) or down-regulation (i.e., FAs, MAPK, JAK/STAT, and TGF-ß) were classic in the maintenance of hESC phenotype Real time PCR confirmed that the expression of focal adhesion (PTK2, VCL, and CXCL14) and MAPK signaling (CAV1) related genes was down-regulated 2-3 folds compared to the flat control. Altogether, cSAP enhances the pluripotency and the hematopoietic potential of hESCs that subsequently generates more blood-like cells. This study reveals the potential of cSAPs on the expansion and early-stage blood cell lineage differentiation of hPSCs.

The distinct effects of P18 overexpression on different stages of hematopoiesis involve TGF-ß and NF-κB signaling.

Deficiency of P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of P18 overexpression, which is involved in the inhibitory effects of RUNX1b at the early stage of hematopoiesis, have not been examined in detail. In this study, we established inducible P18/hESC lines and monitored the effects of P18 overexpression on hematopoietic differentiation. Induction of P18 from day 0 (D0) dramatically decreased production of CD34highCD43- cells and derivative populations, but not that of CD34lowCD43- cells, changed the cell cycle status and apoptosis of KDR+ cells and downregulated the key hematopoietic genes at D4, which might cause the severe blockage of hematopoietic differentiation at the early stage. By contrast, induction of P18 from D10 dramatically increased production of classic hematopoietic populations and changed the cell cycle status and apoptosis of CD45+ cells at D14. These effects can be counteracted by inhibition of TGF-ß or NF-κB signaling respectively. This is the first evidence that P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs).

Effect of curcumin on the non-alcoholic steatohepatitis via inhibiting the M1 polarization of macrophages.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global medical problem and macrophages' activation is closely related to the pathogenesis of NASH. Curcumin is a polyphenol from turmeric with significant anti-inflammatory activity. OBJECTIVE: The objective of present study was to observe the effect of curcumin on macrophages' activation and secretion of pro-inflammatory cytokines in NASH. METHODS: Hematoxylin and eosin and TUNEL staining were used to observe the hepatic function. RT-PCR was conducted to evaluate the hepatic mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Flow cytometry was adopted to detect the M1 polarization of macrophages. The RAW264.7 macrophage was pretreated with different doses of curcumin, and then lipopolysaccharide (LPS) and interferon-γ (IFN-γ) were given to activate the M1 macrophage. The activation ratio of M1 macrophage was observed by flow cytometry, and IL-1ß and TNF-α expression was detected by RT-PCR and ELISA. RESULTS: After treatment with curcumin, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the mRNA expression of TNF-α and IL-1ß, and M1 polarization of macrophages were significantly decreased. Hematoxylin and eosin and TUNEL staining showed that inflammation and apoptosis in the liver were improved. What is more, curcumin can effectively inhibit M1 macrophage activation induced by lipopolysaccharide and IFN-γ and reduce the secretion of IL-1ß and TNF-α. CONCLUSION: Curcumin can effectively improve NASH and reduce hepatic cell necrosis by inhibiting the M1 polarization of macrophages and the secretion of inflammatory factors.

Symptom trajectories and influencing factors of prostate cancer following radical prostatectomy in Chinese patients.

BACKGROUND: Patients following radical prostatectomy will encounter various symptoms that may vary depending on the recovery of surgery and the use of adjuvant treatments. However, few studies have used the scale developed for prostate cancer to longitudinally assess the course of symptoms in Chinese patients. This study aimed to identify the symptom trajectories and the influencing factors in the prostate cancer patients of our area. METHODS: A prospective observational study was conducted, and 155 patients with prostate cancer from 3 hospitals in Shanghai were recruited. Demographic and disease-related information was collected during the hospitalization. Further information on symptoms, adjuvant treatment, and functional exercise was collected across 4 time points. Growth mixture modeling was used to identify the trajectory patterns of symptoms, and logistic regression was used to determine the predictors. RESULTS: A total of 143 patients completed the investigation of all points, with a lost-to-follow-up rate of 7.7%. Urinary incontinence, urinary tract irritation, sexual dysfunction, pelvic pain, and hormone related symptoms all had group heterogeneity, and the number of latent category trajectories obtained was 4, 3, 3, 4, and 3 respectively. There were differences in demographic, disease, and treatment-related information between the groups. CONCLUSIONS: Patients with prostate cancer have different symptom levels across different periods after radical prostatectomy. Medical staff can predict these changes based on the initial level of symptoms and related factors such as age, prostate volume, medical comorbidities, drug of adjuvant treatment to clarify the critical points, populations, and symptoms that require monitoring during follow-up.

Overexpression of HOXA9 upregulates NF-κB signaling to promote human hematopoiesis and alter the hematopoietic differentiation potentials.

BACKGROUND: The HOX genes are master regulators of embryogenesis that are also involved in hematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles in hematopoiesis and leukemogenesis. METHODS: We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normal pluripotency and potential for hematopoiesis, which could be used to analyze gene function with high accuracy. HOXA9/hESCs co-cultured with aorta-gonad-mesonephros-derived stromal cells (AGM-S3) were induced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started and then subjected to flow cytometry. RESULTS: Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increased the production of CD34+ cells and derived populations. The potential for myelogenesis was significantly elevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion of S phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κB signaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could be counteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX. CONCLUSIONS: Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promoted hematopoiesis and the production of myeloid progenitors while reduced the production of erythroid progenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoietic lineages.

First case of COVID-19 complicated with fulminant myocarditis: a case report and insights.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

RUNX1-205, a novel splice variant of the human RUNX1 gene, has blockage effect on mesoderm-hemogenesis transition and promotion effect during the late stage of hematopoiesis.

Runt-related transcription factor 1 (RUNX1) is required for definitive hematopoiesis; however, the functions of most human RUNX1 isoforms are unclear. In particular, the effects of RUNX1-205 (a novel splice variant that lacks exon 6 in comparison with RUNX1b) on human hematopoiesis are not clear. In this study, a human embryonic stem cell (hESC) line with inducible RUNX1-205 overexpression was established. Analyses of these cells revealed that induction of RUNX1-205 overexpression at early stage did not influence the induction of mesoderm but blocked the emergence of CD34+ cells, and the production of hematopoietic stem/progenitor cells was significantly reduced. In addition, the expression of hematopoiesis-related factors was downregulated. However, these effects were abolished when RUNX1-205 overexpression was induced after Day 6 in co-cultures of hESCs and AGM-S3 cells, indicating that the inhibitory effect occurred prior to generation of hemogenic endothelial cells, while the promotive effect could be observed during the late stage of hematopoiesis. This is very similar to that of RUNX1b. Interestingly, the mRNA expression profile of RUNX1-205 during hematopoiesis was distinct from that of RUNX1b, and the protein stability of RUNX1-205 was much higher than that of RUNX1b. Thus, the function of RUNX1-205 in normal and diseased models should be further explored.

HOXC4 up-regulates NF-κB signaling and promotes the cell proliferation to drive development of human hematopoiesis, especially CD43+ cells.

The hematopoietic function of HOXC4 has not been extensively investigated. Our research indicated that induction of HOXC4 in co-culture system from D10 significantly promoted productions of most hematopoietic progenitor cells. CD34-CD43+ cells could be clearly classified into CD34-CD43low and CD34-CD43high sub-populations at D14. The former cells had greater myelogenic potential, and their production was not significantly influenced by induction of HOXC4. By contrast, the latter cells had greater potential to differentiate into megakaryocytes and erythroid cells, and thus had properties of erythroid-megakaryocyte common progenitors, which abundance was increased by ∼2-fold when HOXC4 was induced from D10. For CD34-CD43low, CD34+CD43+, and CD34-CD43high sub-populations, CD43 level served as a natural index for the tendency to undergo hematopoiesis. Induction of HOXC4 from D10 caused more CD43+ cells sustain in S-phase with up-regulation of NF-κB signaling, which could be counteracted by inhibition of NF-κB signaling. These observations suggested that promotion of hematopoiesis by HOXC4 is closely related to NF-κB signaling and a change in cell-cycle status, which containing potential of clinical applications.

Effects of cadmium-resistant plant growth-promoting rhizobacteria and Funneliformis mosseae on the cadmium tolerance of tomato (Lycopersicon esculentum L.).

Microorganisms are used to alleviate heavy metal stress in plants cultivated in contaminated fields. However, the relevant mechanisms have been rarely explored. The goal of this study was to investigate effects of arbuscular mycorrhizal fungus Funneliformis mosseae and two Cd-resistant bacterial strains (Enterobacter sp. EG16 and Enterobacter ludwigii DJ3) on growth and Cd tolerance of tomato when applied with different inoculation strategies (single or dual) and Cd concentrations (50 and 100 mg kg-1). Better plant growth was observed in mycorrhizal alone or combined treatments. In F. mosseae and EG16 co-inoculation treatment, shoot and root dry weight were 119-154% and 91-173% higher than those of the control, respectively. Higher bacterial and mycorrhizal colonization rate and root Cd concentration were also found in this treatment. However, the decrease of shoot Cd concentration and translocation factor values indicated this treatment was effective in improving Cd tolerance of the host plants. In addition, the increase in soil pH and decline in bioavailable Cd in the rhizosphere might be partly involved in reduction of Cd accumulation in plants. Our results suggest that co-inoculation with suitable microorganisms is important in plant growth and tolerance to Cd in Cd-contaminated soil.

Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis.

BACKGROUND: The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis. MATERIALS AND METHODS: To diagnosis of GHD, the Body Mass Index (BMI), Insulin Like Growth Factor-1(IGF-1) and peak growth hormone (GH) values after insulin stimulation test of 15 aCP patients were recorded. Histological staining was performed on the aCP samples. Levels of 9 proinflammatory cytokines in tumor tissue and cell supernatant were detected using Millipore bead arrays. The effect of IL-1α on GH secretion was evaluated in vivo and in vitro. Western blot, qRT-PCR and cell functional assays were used to explore the potential mechanism through which IL-1α acts on GH secretion. The stereotactic ALZET osmotic pump technique was used to simulate aCP secretion of proinflammatory cytokines in rats. Recombinant IL-1α (rrIL-1α) and conditioned media (CM) prepared from the supernatant of aCP cells was infused directly into the intra-sellar at a rate of 1 µl/h over 28 days, and then the effects of IL-1α treatment on pathological changes of pituitary gland and GH secretion were measured. To further confirm whether IL-1α affects GH secretion through IL-1R1, an IL-1R1 blocker (IL-1R1a, 10 mg/kg body weight, once daily) was administered subcutaneously from the first day until day 28. RESULTS: There was a significant positive correlation between pituitary fibrosis and GHD (rS = 0.756, P = 0.001). A number of cytokines, in particular IL-1α, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), were elevated in tumor tissue and cell supernatant. Only IL-1α showed a significant difference between the GHD group and the No-GHD group (P < 0.001, F = 6.251 in tumor tissue; P = 0.003, F = 1.529 in cell supernatant). IL-1α significantly reduced GH secretion in coculture of GH3 and pericytes. The activation of pericytes induced by IL-1α was mediated by the IL-1R1 signaling pathway. In vivo, IL-1α induces pituitary fibrosis, further leading to a decreased level of GH. This pathological change was antagonized by IL-1R1a. CONCLUSION: This study found that the cross talk between aCP cells and stroma cells in the pituitary, i.e. pericytes, is an essential factor in the formation of GHD, and we propose that neutralization of IL-1α signaling might be a potential therapy for GHD in aCP.