Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC). OSCC is ...characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP) and induced cytochrome c and apoptosis inducing factor (AIF) release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER) stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways.
Recent studies have shown that free fatty acids are associated with chronic inflammation, which may be involved in vascular injury. The intake of eicosapentaenoic acid (EPA) can decrease ...cardiovascular disease risks, but the protective mechanisms of EPA on endothelial cells remain unclear. In this study, primary human umbilical vein endothelial cells (HUVECs) treated with palmitic acid (PA) were used to explore the protective effects of EPA. The results revealed that EPA attenuated PA-induced cell death and activation of apoptosis-related proteins, such as caspase-3, p53 and Bax. Additionally, EPA reduced the PA-induced increase in the generation of reactive oxygen species, the activation of NADPH oxidase, and the upregulation of inducible nitric oxide synthase (iNOS). EPA also restored the PA-mediated reduction of endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK) phosphorylation. Using AMPK siRNA and the specific inhibitor compound C, we found that EPA restored the PA-mediated inhibitions of eNOS and AKT activities via activation of AMPK. Furthermore, the NF-κB signals that are mediated by p38 mitogen-activated protein kinase (MAPK) were involved in protective effects of EPA. In summary, these results provide new insight into the possible molecular mechanisms by which EPA protects against atherogenesis via the AMPK/eNOS-related pathway.
•Under investigation in this paper is a (2+1)-dimensional Broer-Kaup-Kupershmidt system for the nonlinear and dispersive long gravity waves on two horizontal directions in the shallow water of ...uniform depth. Bilinear forms, Bäcklund transformation and Lax pair are derived based on the Bell polynomials and symbolic computation.•One- and two-soliton solutions with a real function Φ (y) are constructed via the Hirota method, where y is the scaled space coordinate.•Propagation and interaction of the solitons are illustrated graphically: (i)Φ(y) affects the shape of the solitons. (ii) Interaction of the solitons including the elastic and inelastic interactions are discussed. When the solitons’ interaction is elastic, the amplitude, velocity and shape of the soliton remain invariant after the interaction except for a phase shift, and the smaller-amplitude soliton has a larger phase shift. (iii) Height of the water surface above a horizontal bottom can be a bell-shaped soliton or an upside-down bell-shaped soliton under certain conditions, while horizontal velocity of the water wave always keeps bell-shaped.
Under investigation in this paper is a (2+1)-dimensional Broer-Kaup-Kupershmidt system for the nonlinear and dispersive long gravity waves on two horizontal directions in the shallow water of uniform depth. Bilinear forms, Bäcklund transformation and Lax pair are derived based on the Bell polynomials and symbolic computation. One- and two-soliton solutions with a real function ϕ(y) are constructed via the Hirota method, where y is the scaled space coordinate. Propagation and interaction of the solitons are illustrated graphically: (i) ϕ(y) affects the shape of the solitons. (ii) Interaction of the solitons including the elastic and inelastic interactions are discussed. When the solitons’ interaction is elastic, the amplitude, velocity and shape of the soliton remain invariant after the interaction except for a phase shift, and the smaller-amplitude soliton has a larger phase shift. (iii) Height of the water surface above a horizontal bottom can be a bell-shaped soliton or an upside-down bell-shaped soliton under certain conditions, while horizontal velocity of the water wave always keeps bell-shaped.
Severe infection commonly results in immunosuppression, which leads to impaired pathogen clearance or increased secondary infection in both humans and animals. However, the exact mechanisms remain ...poorly understood. Here, we demonstrate that IL-33 results in immunosuppression by inducing thymic involution-associated naive T cell dysfunction with aberrant expression of aging-associated genes and impairs host control of infection in mouse disease models of schistosomiasis or sepsis. Furthermore, we illustrate that IL-33 triggers the excessive generation of medullary thymic epithelial cell (mTEC) IV (thymic tuft cells) in a Pou2f3-dependent manner, as a consequence, disturbs mTEC/cortical TEC (cTEC) compartment and causes thymic involution during severe infection. More importantly, IL-33 deficiency, the anti-IL-33 neutralizing antibody treatment, or IL-33 receptor ST2 deficient thymus transplantation rescues T cell immunity to better control infection in mice. Our findings not only uncover a link between severe infection-induced IL-33 and thymic involution-mediated naive T cell aging, but also suggest that targeting IL-33 or ST2 is a promising strategy to rejuvenate T cell immunity to better control severe infection.
In this paper we aim to implement a highly distributed information infrastructure—MADIP by using Intelligent Agent paradigm, which is able to notify the responsible care-provider of abnormality ...automatically, offer distance medical advice, and perform continuous health monitoring for those who need it. To confront the issues of interoperability, scalability, and openness in heterogeneous e-health environments, a FIPA2000 standard compliant agent development platform—JADE (Java Agent DEvelopment Framework) was adopted for the design and implementation of the proposed intelligent multi-agent based MADIP system.
Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships ...between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.
Adequate global sourcing makes a strategic difference to an organization's ability to reduce cost and improve the quality of its product. However, the global sourcing makes the process of supplier ...selection riskier and more complex. The data required for confronting the criteria needs to be specific and up-to-date. Now that we have entered the Big Data era with the prominence of social media and social networks such as Twitter, Facebook, LinkedIn; we now have access to global insights and knowledge regarding international suppliers. In this research, we propose a Twitter Enabled Supplier Status Assessment (TESSA) tool that can assist companies in their global supplier selection process. TESSA firstly retrieves a target supplier's related information from the most popular microblog Twitter and then obtains potential risk and uncertainty regarding the supplier through text mining. The discovered risks and uncertainties for companies making better decision on their global supplier selection process.
A growing corpus of evidence implicates the involvement of the commensal microbiota and immune cytokines in the initiation and progression of systemic lupus erythematosus (SLE). Glucocorticoids have ...been widely used in the treatment of SLE patients, however, glucocorticoid treatment carries a higher risk of other diseases. Using the 16S rRNA technique, we investigated the differences between the gut microbiota associated with the immune cytokines of SLE and relevant glucocorticoid treatment in a female cohort of 20 healthy control subjects (HC), 17 subjects with SLE (SLE-G), and 20 SLE patients having undergone glucocorticoid treatment (SLE+G). We observed that the diversity and structure of the microbial community in SLE+G patients were significantly changed compared to that of SLE-G patients, whereas the gut microbial community of the SLE+G group showed a similarity with the HC group, which implicate that the shift in the gut microbiome could represent a return to homeostasis. Furthermore, the up-regulations of immune cytokines in SLE-G were identified as closely related to gut dysbiosis, which indicates that the overrepresented genera in SLE patients may play roles in regulating expression level of these immune cytokines. This associated analysis of gut microbiota, glucocorticoid therapy, and immune factors might provide novel and insightful clues revealing the pathogenesis of SLE patients.
An electrophilic substitution reaction, without acid and metal, of indole with ammonium tetramethylnitrate for accessing 3-nitroindole has been developed. In this protocol, trifluoroacetyl nitrate ...(CF
3
COONO
2
) was produced by metathesis of ammonium tetramethyl nitrate and trifluoroacetic anhydride at sub-room temperature. Trifluoroacetyl nitrate (CF
3
COONO
2
) is an electrophilic nitrating agent for a variety of indoles, aromatic and heterocyclic aromaticity. Meanwhile, this strategy could be applied to construct the skeleton structure of many kinds of bioactive molecules. Interestingly, 3-nitroindole can be further derivatived as a pyrrolo2,3-
b
indole.
An electrophilic substitution reaction, without acid and metal, of indole with ammonium tetramethylnitrate for accessing 3-nitroindole has been developed.
The penetration depth and the power density of photobiomodulation (PBM) in human tissue under real conditions remain unclear to date. A novel quantitative measurement method was proposed in this ...study. This study aimed to design a noninvasive measurement system for the quantitative calculation of PBM dose on the attached gingiva. A flexible facial fixture appliance (FFFA) and nine piece detectors were mounted on the retainer to detect the real dose of 660 and 830 nm lasers on the attached gingiva. In addition, the angular distribution of light scattering and the light propagation in the biotissue were obtained. Two cases (a female and a male) are presented in this study. Experimental results demonstrated that the real power density of laser in the target tissue can be measured exactly after the laser light penetrates the orbicularis oris. Simulation results match with real conditions. Conversely, slight differences in power density are observed in the tissue radiated with collimated and uncollimated laser. The proposed method can be used to calculate the real dose in the target tissue for stomatology and deep acupoint stimulation.
PDF
