There is growing evidence for a connection between inflammation and tumor development, and the nuclear factor kappa B (NF-B), a proinflammatory transcription factor, is hypothesized to promote tumorigenesis. Although the genetic evidence for the hypothesis has been lacking, recent papers have lent credence to this hypothesis. It has been reported that constitutive NF-B activation in inflammatory bowel diseases (

Background & Aims Constitutive activation of NF-κB and STAT3 pathways in human colorectal cancers links inflammation to CRC development and progression. However, the underlying mechanisms remain to be elucidated. Here we investigated the roles of miR-221 and miR-222 in regulating both NF-κB and STAT3 activities and colorectal tumorigenesis. Methods miR-221/222 mimics and their inhibitors/sponges were transiently or stably transfected into cells. Dual luciferase reporter assays were utilized to examine the activation of both NF-κB and STAT3 signaling, as well as the regulation of miR-221/222. Quantitative PCR and immunoblot analysis were employed to examine the mRNA and protein expression. MTT assay, flow cytometric analysis and xenotransplant of tumor cells were performed to investigate the CRC cell growth in vitro and in vivo. Results miR-221 and miR-222 positively regulate both NF-κB and STAT3 activities, which in return induce miR-221/222 expression, creating a positive feedback loop in human CRCs. miR-221/222 directly bind to the coding region of RelA, leading to increased RelA mRNA stability. In addition, miR-221/222 reduce ubiquitination of RelA and STAT3 proteins by directly targeting the 3′ UTR of PDLIM2, an E3 ligase for both RelA and STAT3. We demonstrate that disruption of the positive feedback loop suppresses human CRC cell growth in vitro and in vivo. The expression of miR-221/222 correlates with the expression of RelA, STAT3 and PDLIM2 in human CRC clinical samples. Conclusions Our findings define a novel miR-221/222 mediated mechanism underlying constitutive activation of NF-κB and STAT3 pathways in human CRCs and provide a promising therapeutic target for human CRCs.

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Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGFβ signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGFβ treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.

Schistosoma egg-induced liver granuloma is a dynamic inflammatory reaction that results from complex immune responses to the infection. However, the role of B cells in inflammatory granuloma development is not yet fully understood. We report here that B cell function is required for S. japonicum egg-induced granuloma pathology in early infection. Both OBF-1 knockout mice and µMT mice develop severely reduced hepatic granulomas at five weeks post-infection compared to their wild-type counterparts. In contrast, they display no significant difference in granuloma pathology at eight weeks post-infection. Moreover, we find that B cells and antibodies accumulate in the granulomas of wild-type mice early in the infection, indicating a contribution of the B cell response to the granulomatous inflammation. Furthermore, defects in B cell function markedly reduce liver egg burden. These results suggest an important role for B cells in early granuloma pathology. Surprisingly, we found that the S. japonicum infection destroys the structure of the lymphoid follicles. This disruptive effect is correlated with a severely impaired T cell-dependent antibody response upon challenge with ovalbumin. Thus, these findings reveal a novel aspect of the interaction between Schistosoma and the host immune system.

miR-449a has been reported to act as a tumor suppressor in several cancers, however, it is controversial whether it inhibits tumor growth in colorectal cancer. The mechanisms underlying its expression and functions in colorectal cancers are still largely unknown. SATB2 is a sensitive and specific marker for CRC diagnosis. However, the mechanisms by which the expression and functions of SATB2 are regulated still remain to be clarified. We investigated the expression and functional significance of miR-449a and SATB2 and the mechanisms of their dysregulation in human CRC cells. miR-449a overexpression or SATB2 depletion inhibited tumor growth and promoted apoptosis in colorectal tumor cells in vitro and in xenograft mouse model, partially by downregulating SATB2. Expression of miR-449a was increased epigenetically via knocking down their targets, particularly SATB2. miR-449a was downregulated and STAB2 expression was upregulated in human CRCs. Their expressions were significantly associated with overall survival of CRC patients. Our findings demonstrate the existence of a miR-449a-SATB2 negative feedback loop that maintains low levels of miR-449a as well as high level of SATB2, thereby promoting CRC development.

Flexible optical sensors are widely studied and applied in many fields. However, developing highly stable and washable wearable sensors in optics is still facing significant challenges. Here, we demonstrate an AIEgen–organosilica framework (TPEPMO) hybrid nanostructure-based flexible optical sensor, which is prepared by a two-step co-condensation and electrospinning superassembly process. Organosilica precursors with aggregation-induced emission (AIE) features are covalently linked into periodic mesoporous organosilica (PMO) frameworks with high fluorescent efficiency due to the restriction of intramolecular motion. The three-dimensional space of ordered porous materials provides abundant reaction sites, allowing rapid and sensitive monitoring of analytes. TPEPMOs exhibit good properties as acidic pH fluorescent sensors with a pK a of 4.3. A flexible film is obtained by dispersing TPEPMO nanospheres in a poly­(lactic-co-glycolic acid) (PLGA) and polyacrylonitrile (PAN) hybrid fibrous matrix (TPEPMO-CFs) using the electrospinning superassembly technique and is successfully served as an efficient fluorescent probe for the naked eye detection of ammonia gas and HCl vapor by emission changes. The fluorescence of TPEPMO-CFs can be reversed in the presence of volatile acidic/alkaline gas for more than five cycles, exhibiting excellent recyclability. In addition, TPEPMO-CF sensors show excellent washability and long-term photostability (fluorescence was maintained above 94% after washing 10 times). These stimuli-responsive AIEgen–organosilica frameworks featuring diversified forms and superstability for wearable and washable solid-state fluorescence exhibit great potential for smart gas sensors, wearable devices, and solid-state lighting applications.

We present a method to characterize the wettability of powders, based on the penetration dynamics of a sessile drop deposited on a slightly compressed powder bed. First, we show that a direct comparison of the wetting properties of different liquids is possible without having to solve the three-dimensional liquid penetration problem, by considering the appropriate dimensionless variables. We show that the contact area between the sessile drop and the powder bed remains constant during most of the penetration process and demonstrate that as a result, the evolution of the dimensionless penetration volume is given by a universal function of the dimensionless time, with no dimensionless parameters. Then, using a reference liquid that completely wets the powder, it is possible to obtain an effective contact angle for a test liquid of interest, independent of other properties of the powder bed, such as permeability and a characteristic pore size. We apply the proposed method to estimate the contact angle of water with different powder blends, by using silicone oil as the reference liquid. Finally, to highlight the potential of the proposed method to characterize pharmaceutical powders, we consider a blend of lactose, acetaminophen, and a small amount of lubricant (magnesium stearate). The proposed method adequately captures a significant decrease in hydrophilicity that results from exposing the blend to excessive mixing, a well-known effect in the pharmaceutical industry.