Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune ...responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades. BMB Reports 2019; 52(7): 415-423.
The present study intends to develop and validate a multidimensional evaluation standard for customers' participation in corporate social responsibility (CSR) value co‐creation (VCC), which has grown ...exponentially since the start of the Internet commonweal platform era. A Delphi study was conducted with a group of 30 professionals and local community members. Initial items for measuring CSR VCC were derived from the Delphi study. These items were then used to devise a questionnaire that was ultimately administered to 844 customers. Exploratory and confirmatory factor analysis resulted in 28 items based on five factors: customer participation, customer response, corporate response, interaction, and sustainability. Both convergent validity and discriminant validity were verified between factors. Finally, structural equation modeling was used to verify the nomological validity of the scale. This evaluation scale is expected to provide a criterion that can help companies effectively manage CSR aspects of corporate‐customer VCC and help customers choose CSR campaigns they can trust.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Corn starch was gelatinized by high hydrostatic pressure (HHP) and spray drying to make amorphous granular starch (AGS), and their physicochemical properties were compared with the conventionally ...prepared (heat-gelatinized and spray dried) AGS to devise a novel AGS preparation methodology. Pressure-induced (PAGS) and heat-induced AGS (HAGS) maintained their granular shape but lost their birefringence indicating that both methods could prepare AGS. DSC (differential scanning calorimeter) and XRD (X-ray diffraction) analysis confirmed the complete loss of amylopectin double helices and crystallinity of both PAGS and HAGS. However, their swelling power, solubility, RVA pasting properties, acid/shear stability, gel forming ability and textural properties were completely different. PAGS exhibited constrained swelling, suppressed amylose leaching, and reduced viscosity. Notably, HAGS formed a gel without heating, whereas PAGS yielded a viscous paste with water-soluble attributes. Even after reheating, PAGS maintained its granular structure with comparably less swelling and weaker gel strength than HAGS. Consequently, newly developed PAGS exhibited distinctive characteristics compared to the conventional HAGS, such as lower solubility and swelling power, viscosity, textural properties, and high acid and shear stabilities, rendering it a viable option for various applications within the food industry.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Natural surfaces excel in self-renewal and preventing bio-fouling, while synthetic materials placed in contact with complex fluids quickly foul1,2. We present a novel biophysics-inspired mechanism3,4 ...for surface renewal using actuating surface topography, generated by wrinkling. We calculate a critical surface curvature, given by an intrinsic characteristic length scale of the fouling layer that accounts for its effective flexural or bending stiffness and adhesion energy, beyond which surface renewal occurs. The effective bending stiffness includes the elasticity and thickness of the fouling patch, but also the boundary layer depth of the imposed wrinkled topography. The analytical scaling laws are validated using finite-element simulations and physical experiments. Our data span over five orders of magnitude in critical curvatures and are well normalized by the analytically calculated scaling. Moreover, our numerics suggests an energy-release mechanism whereby stored elastic energy in the fouling layer drives surface renewal. The strategy is broadly applicable to any surface with tunable topography and fouling layers with elastic response.
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IJS, NUK, SBMB, UL, UM, UPUK
Diabetes mellitus (DM) characterized by hyperglycemia leads to a variety of complications, including cognitive impairment or memory loss. The hippocampus is a key brain area for learning and memory ...and is one of the regions that is most sensitive to diabetes. However, the pathogenesis of diabetic neuronal lesion is not yet completely understood. We focused on the association of microglia activation and brain lesions in diabetes. In this study, we investigated whether and how signal transducer and activator of transcription 3 (STAT3) activation in microglia affects neuronal lesions in diabetic brains. Using a streptozotocin‐induced type 1 DM model, we showed enhanced hippocampal neuronal apoptosis that was associated with increased STAT3 activation. We found that hyperglycemia increased the expression of inflammatory cytokines such as interferon‐γ (IFN‐γ) and interleukin‐6, in the diabetic hippocampus. In particular, IFN‐γ induced autocrine activation of microglia, and STAT3 activation is important for this process. We also demonstrated that STAT3 activation in microglia increased tumor necrosis factor‐α (TNF‐α) expression; subsequently, TNF‐α increased neuronal apoptosis by increasing reactive oxygen species (ROS) levels in the neuronal cells. We also took advantage of mice lacking STAT3 in microglia and demonstrated that depletion of microglial STAT3 reduced neuronal apoptosis in the diabetic hippocampus. Taken together, these results suggest that STAT3 activation in microglia plays an important role in hyperglycemia‐induced neuronal apoptosis in the diabetic hippocampus and provide a potential therapeutic benefit of STAT3 inhibition in microglia for preventing diabetic neuronal lesions.
We demonstrated that signal transducer and activator of transcription 3 (STAT3) activation in microglia exacerbates neuronal apoptosis of the diabetic hippocampus and that increased tumor necrosis factor‐α (TNF‐α) through STAT3 activation causes neuronal apoptosis. We also took the advantage of mice lacking STAT3 in microglia and demonstrated that depletion of microglial STAT3 reduced neuronal apoptosis in the diabetic hippocampus. There results suggest that STAT3 activation in microglia plays an important role in hyperglycemia‐induced neuronal apoptosis in the diabetic hippocampus and provide a potential therapeutic benefit of STAT3 inhibition in microglia for preventing diabetic neuronal lesions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most lethal neoplasm, causing an estimated 700000 deaths annually. Currently HCC has only one systemic molecular targeted ...therapy, the multi-kinase inhibitor, sorafenib. The standard-of-care for advanced liver cancer is limited because sorafenib can expand the median life expectancy of patients for only 1 year. Thus there is an urgent need to develop a novel molecular targeted therapy to improve therapeutic outcomes for HCC. HCCs are phenotypically and genetically heterogeneous tumors driven by diverse molecular mechanisms. However, HCCs exhibit certain common traits selected through genetic and epigenetic alterations. The identification of common molecular alterations may provide an opportunity to develop more effective anticancer treatment through targeted therapy. Recent studies in liver cancer biology have revealed a limited number of molecular targets responsible for initiating and maintaining dysregulated cell proliferation, including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), c-mesenchymal-epithelial transition factor-1 (c-Met), mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). New treatments involving inhibitors targeting several of these critical pathways are in development. This review describes the current understanding of target pathways, ongoing clinical trials using HCC-targeted agents, and future directions in the treatment of HCC.
Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and ...identification of high-risk patients for early intervention are challenging. Using a large computed tomography (CT) database from 3,777 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19.
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•AI system that can diagnose COVID-19 pneumonia using CT scans•Prediction of progression to critical illness•Potential to improve performance of junior radiologists to the senior level•Can assist evaluation of drug treatment effects with CT quantification
Zhang et al. present an AI-based system, based on hundreds of thousands of human lung CT scan images, that can aid in distinguishing patients NCP versus other common pneumonia and can help to predict the prognosis of COVID-19 patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its ...clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling up‐regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL‐6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL‐6, with a concomitant decrease of hypoxia‐inducible factor 1 alpha (HIF‐1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF‐κB) p65 subunit to positively regulate the transcription of HIF‐1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF‐1α and CD133 expression were not observed in Toll‐like receptor 4/IL‐6 double‐knockout mice. Long‐term silencing of CD133 by a lentiviral‐based approach inhibited cancer cell‐cycle progression and suppressed in vivo tumorigenicity by down‐regulating expression of cytokinesis‐related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF‐1α proteins. Conclusion: IL‐6/STAT3 signaling induces expression of CD133 through functional cooperation with NF‐κB and HIF‐1α during liver carcinogenesis. Targeting STAT3‐mediated CD133 up‐regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. (Hepatology 2015;62:1160‐1173)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of a variety of genes to regulate important biological functions, ...including cell proliferation, differentiation, survival, angiogenesis, and immune response. Constitutive activation of STAT3 is important in oncogenic signaling and occurs at high frequency in human cancers, including diverse solid tumors and hematologic malignancies. Moreover, it is associated with a poor prognosis. The tumor microenvironment has recently been recognized as a key condition for cancer progression, invasion, angiogenesis, metastasis, and drug resistance by activation of STAT3 signaling. Therefore, understanding the biology associated with STAT3-mediated signaling cascades in the tumor microenvironment may offer the therapeutic potential to treat human cancers. This review presents an overview of the critical roles of STAT3 in the tumor microenvironment related to cancer biology and discusses recent advancements in the development of anticancer drugs that therapeutically inhibit STAT3 signaling cascades.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Polydimethylsiloxane (PDMS) is commonly used in medical devices because it is non-toxic and stable against oxidative stress. Relatively high blood platelet adhesion and the need for chemical ...crosslinking through curing, however, limit its utility. In this research, a biostable PDMS-based polyurethane-urea bearing zwitterion sulfobetaine (
PDMS-SB-UU
) was synthesized for potential use in the fabrication or coating of blood-contacting devices, such as a conduits, artificial lungs, and microfluidic devices. The chemical structure and physical properties of synthesized
PDMS-SB-UU
were confirmed by
1
H-nuclear magnetic resonance (
1
H-NMR), X-ray diffraction (XRD), and uniaxial stress-strain curve.
In vitro
stability of
PDMS-SB-UU
was confirmed against lipase and 30% H
2
O
2
for 8 weeks, and
PDMS-SB-UU
demonstrated significantly higher resistance to fibrinogen adsorption and platelet deposition compared to control PDMS. Moreover,
PDMS-SB-UU
showed a lack of hemolysis and cytotoxicity with whole ovine blood and rat vascular smooth muscle cells (rSMCs), respectively. The
PDMS-SB-UU
was successfully processed into small-diameter (0.80 ± 0.05 mm) conduits by electrospinning and coated onto PDMS- and polypropylene-based blood-contacting biomaterials due to its unique physicochemical characteristics from its soft- and hard- segments.
Development and processing of a biostable, anti-fouling zwitterionic polyurethane-urea based on PDMS for blood-contacting medical devices.
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