Stem cell factor SALL4, a potential prognostic marker for myelodysplastic syndromes

Background: Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases with variable clinical course. Predicting disease progression is difficult due to lack of specific molecular marker(s). SALL4 plays important roles in normal hematopoiesis and leukemogenesis. SALL4 transgenic mice develop MDS prior to acute myeloid leukemia (AML) transformation. However, the role of SALL4 in human MDS has not been extensively investigated. In this study, we evaluate the diagnostic/prognostic value of SALL4 in MDS by examining its expression levels in a cohort of MDS patients. Methods: Fifty-five newly diagnosed MDS, twenty MDS-AML, and sixteen post-treatment MDS patients were selected for our study along with ten healthy donors. Results: We demonstrated that SALL4 was over-expressed in MDS patients and proportionally increased in MDS patients with high grade/IPSS scores. This expression pattern was similar to that of Bmi-1, an important marker in predicting MDS/AML progression. In addition, the level of SALL4 was positively correlated with increased blast counts, high-risk keryotypes and increased significantly in MDS-AML transformation. Furthermore, higher level of SALL4 expression was associated with worse survival rates and SALL4 level decreased following effective therapy. Conclusions: To the best of our knowledge, this is the largest series and the first to report the expression pattern of SALL4 in detail in various subtypes of MDS in comparison to that of Bmi-1. We conclude that SALL4 is a potential molecular marker in predicting the prognosis of MDS

Cortisol dysregulation in anxiety infertile women and the influence on IVF treatment outcome

IntroductionDysregulation of the stress-regulatory hormone cortisol is associated with anxiety, but its potential impact on infertile women and in vitro fertilization (IVF) treatment remains unclear. This prospective cross-sectional study aimed at evaluating the dysregulation of cortisol and its correlation to anxiety in infertile women. The influence of stress on IVF outcomes was also investigated.MethodsA point-of-care test was used for the measurement of morning serum cortisol in 110 infertile women and 112 age-matching healthy individuals. A Self-Rating Anxiety Scale (SAS) was used for the anxiety assessment of infertile women, and 109 of them underwent IVF treatment starting with the GnRH-antagonist protocol. If clinical pregnancy was not achieved, more IVF cycles were conducted with adjusted protocols until the patients got pregnant or gave up.ResultsHigher morning serum cortisol level was identified for infertile patients, especially for the elder. Women with no anxiety showed significant differences in cortisol levels, monthly income, and BMI compared with those with severe anxiety. A strong correlation was found between the morning cortisol level and the SAS score. When the cutoff value is 22.25 μg/dL, cortisol concentration could predict the onset of anxiety with high accuracy (95.45%) among infertile women. After IVF treatments, women with high SAS scores (>50) or cortisol levels (>22.25 μg/dL) demonstrated a lower rate of pregnancy (8.0%-10.3%) and more IVF cycles, although the impact of anxiety was not affirmative.ConclusionHypersecretion of cortisol related to anxiety was prevalent among infertile women, but the influence of anxiety on multi-cycle IVF treatment was not affirmative due to the complicated treatment procedures. This study suggested that the assessment of psychological disorders and stress hormone dysregulation should not be overlooked. An anxiety questionnaire and rapid cortisol test might be included in the treatment protocol to provide better medical care

Changes of serum cortisol during pregnancy and labor initiation: an onsite cross-sectional study

BackgroundIncreased maternal cortisol secretion has been observed during pregnancy and labor. However, due to the limitations in diagnostic methods, the dynamic change of cortisol during the short period between threatened labor and labor is unknown. In this study, we aim to evaluate the changes in serum cortisol during late pregnancy and full-term labor initiation, verifying if cortisol could serve as a biomarker for the diagnosis of labor initiation from threatened labor.MethodsThis cross-sectional onsite study involved 564 participants of 6 different gestational stages (C: Control; T1: Trimester 1; T3: Trimester 3; E: expectant; TL: threatened labor; L: labor), all patients in the E, TL, and L groups were at full term. The serum cortisol concentration was quantified with a point-of-care test (POCT), and the gestation, age, parity, and BMI of participants were documented. Morning serum cortisol was collected between 8:00 and 10:00 a.m., except for the TL and L group women who were tested upon arrival or during latent labor. With cortisol levels or all five variables, L was distinguished from TL using machine learning algorithms.ResultsSignificant elevation of cortisol concentration was observed between T1 and T3, or TL and L group (P< 0.001). Women belonging to the E and TL group showed similar gestation week and cortisol levels. Diagnosis of labor initiation using cortisol levels (cutoff = 21.46 μg/dL) yielded sensitivity, specificity, and AUC of 86.50%, 88.60%, and 0.934. With additional variables, a higher specificity (89.29%) was achieved. The diagnostic accuracy of all methods ranged from 85.93% to 87.90%.ConclusionSerum cortisol could serve as a potential biomarker for diagnosis of L form TL. The rapid onsite detection of serum cortisol with POCT could facilitate medical decision-making for admission and special treatments, either as an additional parameter or when other technical platforms are not available

Predictors of tropical cyclone-induced urban tree failure: an international scoping review

Background: Trees are critical components of rural and urban ecosystems throughout the world. While they have adapted to the historic conditions of their native environments, climate change, urbanization, and human-assisted range expansion may test the storm resiliency of many tree species. Objective: In this global multilingual scoping review, we investigate a range of intrinsic (i.e., tree characteristics) and external (i.e., environmental and management) factors which have been used to predict tree failure during tropical cyclones. Design: We searched online databases and journals in English, Chinese, French, Japanese, Portuguese, and Spanish to find peer-reviewed papers and dissertations. We retained papers that used ground-based methods to study tree damage following a tropical cyclone and conducted a statistical analysis of factors that influence tree resistance to damage. From each paper we extracted details of study methods, and the relationships between damage and predictors. Results: Our efforts generated 65 peer-reviewed papers and dissertations that met our final criteria for inclusion (i.e., data on the relative proportion of trees failed/intact as assessed no more than a year after the storm event). Of these papers 37 independent variables were assessed to predict tree failure. Research in both urban and rural settings tends to be concentrated in regions frequently impacted by tropical cyclones. Characteristics of species such as wood density have been studied in rural environments and are also relevant predictors for tree failure in urban trees. Environmental characteristics unique to urban settings such as planting areas surrounded by pavement need further research. Several urban studies demonstrate that risk assessment methods can predict tree failure during a storm. Conclusion: Results can be used by future storm researchers to identify both predictors may warrant inclusion in their models as well as predictors which have yet to be tested. Results can also inform planning and activities that can mitigate tropical cyclone damage to the urban forest

Predictors of tropical cyclone-induced urban tree failure: an international scoping review

BackgroundTrees are critical components of rural and urban ecosystems throughout the world. While they have adapted to the historic conditions of their native environments, climate change, urbanization, and human-assisted range expansion may test the storm resiliency of many tree species.ObjectiveIn this global multilingual scoping review, we investigate a range of intrinsic (i.e., tree characteristics) and external (i.e., environmental and management) factors which have been used to predict tree failure during tropical cyclones.DesignWe searched online databases and journals in English, Chinese, French, Japanese, Portuguese, and Spanish to find peer-reviewed papers and dissertations. We retained papers that used ground-based methods to study tree damage following a tropical cyclone and conducted a statistical analysis of factors that influence tree resistance to damage. From each paper we extracted details of study methods, and the relationships between damage and predictors.ResultsOur efforts generated 65 peer-reviewed papers and dissertations that met our final criteria for inclusion (i.e., data on the relative proportion of trees failed/intact as assessed no more than a year after the storm event). Of these papers 37 independent variables were assessed to predict tree failure. Research in both urban and rural settings tends to be concentrated in regions frequently impacted by tropical cyclones. Characteristics of species such as wood density have been studied in rural environments and are also relevant predictors for tree failure in urban trees. Environmental characteristics unique to urban settings such as planting areas surrounded by pavement need further research. Several urban studies demonstrate that risk assessment methods can predict tree failure during a storm.ConclusionResults can be used by future storm researchers to identify both predictors may warrant inclusion in their models as well as predictors which have yet to be tested. Results can also inform planning and activities that can mitigate tropical cyclone damage to the urban forest

Differential Proteome Analysis of Bone Marrow Mesenchymal Stem Cells from Adolescent Idiopathic Scoliosis Patients

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional deformity of the spine. The cause and pathogenesis of scoliosis and the accompanying generalized osteopenia remain unclear despite decades of extensive research. In this study, we utilized two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) to analyze the differential proteome of bone marrow mesenchymal stem cells (BM-MSCs) from AIS patients. In total, 41 significantly altered protein spots were detected, of which 34 spots were identified by MALDI-TOF/TOF analysis and found to represent 25 distinct gene products. Among these proteins, five related to bone growth and development, including pyruvate kinase M2, annexin A2, heat shock 27 kDa protein, γ-actin, and β-actin, were found to be dysregulated and therefore selected for further validation by Western blot analysis. At the protein level, our results supported the previous hypothesis that decreased osteogenic differentiation ability of MSCs is one of the mechanisms leading to osteopenia in AIS. In summary, we analyzed the differential BM-MSCs proteome of AIS patients for the first time, which may help to elucidate the underlying molecular mechanisms of bone loss in AIS and also increase understanding of the etiology and pathogenesis of AIS

TGF-β Signaling in Progression of Oral Cancer

Oral cancer is a common malignancy worldwide, accounting for 1.9% to 3.5% of all malignant tumors. Transforming growth factor β (TGF-β), as one of the most important cytokines, is found to play complex and crucial roles in oral cancers. It may act in a pro-tumorigenic and tumor-suppressive manner; activities of the former include cell cycle progression inhibition, tumor microenvironment preparation, apoptosis promotion, stimulation of cancer cell invasion and metastasis, and suppression of immune surveillance. However, the triggering mechanisms of these distinct actions remain unclear. This review summarizes the molecular mechanisms of TGF-β signal transduction, focusing on oral squamous cell and salivary adenoid systemic carcinomas as well as keratocystic odontogenic tumors. Both the supporting and contrary evidence of the roles of TGF-β is discussed. Importantly, the TGF-β pathway has been the target of new drugs developed in the past decade, some having demonstrated promising therapeutic effects in clinical trials. Therefore, the achievements of TGF-β pathway-based therapeutics and their challenges are also assessed. The summarization and discussion of the updated knowledge of TGF-β signaling pathways will provide insight into the design of new strategies for oral cancer treatment, leading to an improvement in oral cancer outcomes

Verification of the Efficacy and Safety of Qi-Replenishing Chinese Medicine in Treating Prediabetes: A Meta-Analysis and Literature Review

Background. Qi-replenishing Chinese medicines (QCMs) are used for treating prediabetes in the traditional Chinese medicine (TCM) clinical practice. The aims of this meta-analysis were to (i) verify the efficacy and safety of QCMs in treating prediabetes and (ii) investigate the clinical outcomes between the trials complying with and not complying with the principle of “syndrome differentiation.” Methods. We included only randomized controlled clinical trials (RCTs) whose Jadad scores were not less than 4. The overall clinical outcomes, including the incidence rate of diabetes, normalization of blood glucose, changes in fasting blood glucose (FBG), 2 h postprandial blood glucose, HbA1c, and occurrence of adverse events, were evaluated. Subgroup analyses were performed. Results. A total of 11 RCTs that enrolled 2210 patients with prediabetes were included. We observed that overall treatment with QCMs significantly ameliorated the clinical outcomes of prediabetes without increasing incidence of adverse events. The results of subgroup analyses revealed that prescribing QCMs complying with syndrome differentiation ameliorated all the clinical indices, whereas prescribing not complying with syndrome differentiation could not achieve significant amelioration in FBG and HbA1c levels. Furthermore, the subgroup with syndrome differentiation reported more adverse events. Conclusions. The overall results suggested that QCMs are effective and safe in treating prediabetes. Results of subgroup analyses indicated that the groups with syndrome differentiation presented better efficacy but had a higher occurrence of adverse events. This study indicated the important role of the principle of syndrome differentiation in TCM and that the adverse events of QCMs cannot be ignored in TCM clinical practice

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines

Background. Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. Methods. MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. Results. We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. Conclusion. The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo

Anti-atherosclerosis effect of Angong Niuhuang pill via regulating Th17/Treg immune balance and inhibiting chronic inflammatory on apoE^-/- Mice model of early and mid-term atherosclerosis

Angong Niuhuang Pill (ANP) is a well-known patented Chinese medicine which is used for hundreds of years for treating the central nervous system diseases. Atherosclerosis is a polyaetiological chronic inflammatory vascular disease. Preventing inflammation is fundamental for treating atherosclerosis in early stages. In this study, we investigated the protective effects and possible mechanisms of ANP action on a high-fat diet induced early and mid-term atherosclerosis ApoE-/- mice. The effects of ANP were compared with accepted drug simvastatin. Twelve male C57BL/6J mice were used as the control group, and 60 male ApoE-/- mice were randomly divided into five groups: Model group, Simvastatin group, Low-, Medium-, and High-dose ANP group these groups received, respectively, saline, simvastatin (3.0mg/kg), low-dose ANP (0.25 g/kg), medium-dose ANP (0.50 g/kg), and high-dose ANP (1.0 g/kg), once every other day for 10 weeks. After administration, serum biochemical indices were detected by the automatic biochemical analyzer, the concentrations of IL-6 and IL-10 in the serum were assayed by ELISA, expression levels of IL-1b, TNF-a, MMP-2, MMP-9, CCL2, and its receptor CCR2 in the full-length aorta, and expression levels of transcription factors Foxp3, RORgt in the spleen were assayed via western blotting and RT-qPCR. Flow cytometry was used to analyze Th17 cells and Treg cells. Pathological and histological analysis was completed on aortic root. ANP decreased LDL/HDL ratio, concentrations of IL-6 while increased IL-10 in serum. Moreover, ANP down-regulated the expression levels of IL-1b, TNF-a, MMP-2, MMP-9, CCL2, and CCR2 receptor in the full-length aorta. In addition, ANP decreased Th17 cells and expression levels of transcription factor RORgt, increased Treg cells and expression levels of transcription factor Foxp3. ANP decreased content of collagen fibers and infiltration of inflammatory cells in the aortic root. In conclusion, we demonstrated that ANP has anti-atherosclerosis effects on a high-fat diet induced ApoE-/mice early and mid-term AS model via regulating Th17/Treg balance, inhibiting chronic inflammation, reducing plaque collagen fibers, and reducing inflammatory cells infiltration, to exert its multi-channel multi-target anti-early and mid-term AS effects.</p