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Background: Esophageal cancer (ESCA) is a highly invasive malignant tumor with poor prognosis. This study aimed to discover a generalized and high‐sensitivity immune prognostic signature that could stratify ESCA patients and predict their overall survival, and to discover potential therapeutic drugs by the connectivity map. Methods: The key gene modules significantly related to clinical traits (survival time and state) of ESCA patients were selected by weighted gene coexpression network analysis (WCGNA), then the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a 15‐immune‐related gene prognostic signature. Results: The immune‐related risk model was related to clinical and pathologic factors and remained an effective independent prognostic factor. Enrichment analyses revealed that the differentially expressed genes (DEGs) of the high‐ and low‐risk groups were associated with tumor cell proliferation and immune mechanisms. Based on the gathered data, a small molecule drug named perphenazine (PPZ) was elected. The pharmacological analysis indicates that PPZ could help in adjuvant therapy of ESCA through regulation of metabolic process and cellular proliferation, enhancement of immunologic functions, and inhibition of inflammatory reactions. Furthermore, molecular docking was performed to explore and verify the PPZ‐core target interactions. Conclusion: We succeed in structuring the immune‐related prognostic model, which could be used to distinguish and predict patients' survival outcome, and screening a small molecule drug named PPZ. Prospective studies also are needed to further validate its analytical accuracy for estimating prognoses and confirm the potential use of PPZ for treating ESCA. [ABSTRACT FROM AUTHOR]

Background: Histone deacetylases (HDACs) have been demonstrated to be aberrantly activated in tumorigenesis and cancer development. Thus, HDAC inhibitors (HDACIs) are considered to be promising anti‐cancer therapeutics. However, recent studies have shown that HDACIs promote the migration of many cancer cells. Therefore, there is a need to elucidate the underlying mechanisms of HDACIs on cancer cell migration to establish a combination therapy that overcomes HDACI‐induced cell migration. Methods: KYSE‐150 and EC9706 cells were treated differently. Effects of drugs and siRNA treatment on tumor cell migration and cell signaling pathways were investigated by transwell migration assy. Gene expression for SNAI2 was tested by RT‐qPCR. Western blot analysis was employed to detect the level of E‐cadherin, β‐catenin, vimentin,Slug，ERK1/2, H3, PAI‐1 and BRD4. The effect of drugs on cell morphology was evaluated through phase‐contrast microscopic images. Results: TSA promotes epithelial‐mesenchymal transition (EMT) in ESCC cells by downregulating the epithelial marker E‐cadherin and upregulating mesenchymal markers β‐catenin, vimentin, Slug, and PAI‐1. Knockdown of Slug by siRNA or inhibition of PAI‐1 clearly suppressed TSA‐induced ESCC cell migration and resulted in the reversal of TSA‐triggered E‐cadherin, β‐catenin, and vimentin expression. However, no crosstalk between Slug and PAI‐1 was observed in TSA‐treated ESCC cells. Blocking ERK1/2 activation also inhibited TSA‐induced ESCC cell migration, EMT, and upregulation of Slug and PAI‐1 levels in ESCC cells. Interestingly, inhibition of BRD4 suppressed TSA‐induced ESCC cell migration and attenuated TSA‐induced ERK1/2 activation and upregulation of Slug and PAI‐1 levels. Conclusions: Our data indicate the existence of at least two separable ERK1/2‐dependent signaling pathways in TSA‐mediated ESCC cell migration: an ERK1/2–Slug branch and an ERK1/2‐PAI‐1 branch. Both branches of TSA‐induced ESCC cell migration appear to favor the EMT process, while BRD4 is responsible for two separable ERK1/2‐dependent signaling pathways in TSA‐mediated ESCC cell migration. [ABSTRACT FROM AUTHOR]

As a tumor-associated microRNA (miR), miR-212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR-212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus-mediated gain-of-function demonstrated promotion of ESCC cell migration and invasion when miR-212 was overexpressed, and no effect on cell proliferation. miR-212 resulted in downregulation of the expression of E-cadherin, β-catenin, vimentin and Twist1. Moreover, it led to increased levels of extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinase-9 and urokinase-type plasminogen activator. Furthermore, berberine inhibited miR-212-induced ESCC cell migration, unlike the PI3K inhibitor LY294002, rapamycin (mTOR inhibitor), 5-(Tetradecyloxy)-2-furoic acid (TOFA; an acetyl-CoA carboxylase 1 inhibitor), metformin and propranolol. These data suggest that miR-212 activates multiple signaling cascades and facilitates ESCC cell motility and invasion by promoting the epithelial-mesenchymal transition and degrading the ECM. Berberine may be a potential therapeutic agent against metastasis in patients with ESCC, who express high levels of miR-212. [ABSTRACT FROM AUTHOR]

Impaired wound-healing activity in diabetes could result from several factors, including severely damaged angiogenic responses, which can affect wound healing process to cause delayed wound repair. Mesenchymal stem cells (MSCs) have been shown to enhance wound healing via multiple effects, including promoting angiogenesis both in vitro and in vivo; however, the mechanisms involved in enhancing diabetic wound healing are barely understood. This article reviews the recent literatures on MSCs treatment for promoting angiogenesis or vascularization in diabetic wounds and the potential mechanisms involved, with an emphasis on the role of paracrine soluble factors. Meanwhile, the potential benefits and related risks associated with the therapeutic use of MSCs have been presented and may lead to better understanding of the influence of MSCs without increasing potential risks. Further investigation will be required to determine the molecular basis of paracrine mechanisms and regulated angiogenesis of MSCs for its rational manipulation for impaired angiogenesis repair and diabetic wound healing. [ABSTRACT FROM AUTHOR]

Despite extensive researches in acute lung injury ( ALI) and acute respiratory distress syndrome ( ARDS), current pharmacological therapies and respiratory support are still the main methods to treat patients with ALI and ARDS and the effects remain limited. Hence, innovative therapies are needed to decrease the morbidity and mortality. Because of the proven therapeutic effects in other fields, mesenchymal stem cells ( MSCs) might be considered as a promising alternative to treat ALI and ARDS. Numerous documents demonstrate that MSCs can exert multiple functions, such as engraftment, differentiation and immunoregulation, but now the key researches are concentrated on paracrine factors secreted by MSCs that can mediate endothelial and epithelial permeability, increase alveolar fluid clearance and other potential mechanisms. This review aimed to review the current researches in terms of the effects of MSCs on ALI and ARDS and to analyse these paracrine factors, as well as to predict the potential directions and challenges of the application in this field. [ABSTRACT FROM AUTHOR]

A new measurement and analysis method was proposed to investigate the changes in elbow joint moments that occur with the use of a front-wheeled walker. A strain gauge-based walker instrumentation system was developed to monitor the hand loads during walker-assisted walking and integrated with an upper extremity biomechanical model. Preliminary system data were collected for 12 subjects following informed consent. Bilateral upper extremity kinematic data were acquired with a six-camera motion analysis system. Internal joint moments at the elbow were determined in the three clinical planes using the inverse dynamics method. Results showed that during a walker-assisted gait elbow joint moments mainly distributed in the walker stance period. There was a noted demand on the elbow extensor in the sagittal plane with the greatest record as 0.381 N·m/(kg·m). An interesting “bare phase” of mean elbow joint moments was also found in phase angle −240°–340° of gait cycle. Complete description of elbow joint moments of walker-assisted gait may provide insight into walker use parameters and rehabilitative strategies. [ABSTRACT FROM AUTHOR]