Promyelocytic leukemia protein targets MK2 to promote cytotoxicity.

Promyelocytic leukemia protein (PML) is a tumor suppressor possessing multiple modes of action, including induction of apoptosis. We unexpectedly find that PML promotes necroptosis in addition to apoptosis, with Pml-/- macrophages being more resistant to TNF-mediated necroptosis than wild-type counterparts and PML-deficient mice displaying resistance to TNF-induced systemic inflammatory response syndrome. Reduced necroptosis in PML-deficient cells is associated with attenuated receptor-interacting protein kinase 1 (RIPK1) activation, as revealed by reduced RIPK1[S166] phosphorylation, and attenuated RIPK1-RIPK3-MLKL necrosome complex formation. We show that PML deficiency leads to enhanced TNF-induced MAPK-activated kinase 2 (MK2) activation and elevated RIPK1[S321] phosphorylation, which suppresses necrosome formation. MK2 inhibitor treatment or MK2 knockout abrogates resistance to cell death induction in PML-null cells and mice. PML binds MK2 and p38 MAPK, thereby inhibiting p38-MK2 interaction and MK2 activation. Moreover, PML participates in autocrine production of TNF induced by cellular inhibitors of apoptosis 1 (cIAP1)/cIAP2 degradation, since PML-knockout attenuates autocrine TNF. Thus, by targeting MK2 activation and autocrine TNF, PML promotes necroptosis and apoptosis, representing a novel tumor-suppressive activity for PML.

Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence.

Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

Production of a neutralizing antibody against envelope protein of dengue virus type 2 using the linear array epitope technique.

Dengue virus (DENV; genus Flavivirus) contains a positive-stranded RNA genome. Binding of DENV to host cells is mediated through domain III of the viral envelope protein. Many therapeutic mAbs against domain III have been generated and characterized because of its high antigenicity. We have previously established a novel PCR method named the linear array epitope (LAE) technique for producing monoclone-like polyclonal antibodies. To prove this method could be utilized to produce antibody against epitopes with low antigenicity, a region of 10 aa (V365NIEAEPPFG374) from domain III of the envelope protein in DENV serotype 2 (DENV2) was selected to design the primers for the LAE technique. A DNA fragment encoding 10 directed repeats of these 10 aa for producing the tandem-repeated peptides was obtained and fused with glutathione S-transferase (GST)-containing vector. This fusion protein (GST-Den EIII10-His6) was purified from Escherichia coli and used as antigen for immunizing rabbits to obtain the polyclonal antibody. Furthermore, the EIII antibody could recognize envelope proteins either ectopically overexpressed or synthesized by DENV2 infection using Western blot and immunofluorescence assays. Most importantly, this antibody was also able to detect DENV2 virions by ELISA, and could block viral entry into BHK-21 cells as shown by immunofluorescence and quantitative real-time PCR assays. Taken together, the LAE technique could be applied successfully for the production of antibodies against antigens with low antigenicity, and shows high potential to produce antibodies with good quality for academic research, diagnosis and even therapeutic applications in the future.

Orbital hemangiopericytoma in an Asian population.

BACKGROUND/PURPOSE: Hemangiopericytoma is a very rare orbital tumor. The purpose of this study was to report the clinical and histopathological features of six cases of orbital hemangiopericytoma in an Asian population. METHODS: Clinical and histopathological features were reviewed in six patients who were histopathologically confirmed as having primary orbital hemangiopericytoma in National Taiwan University Hospital between May 2001 and December 2010. RESULTS: Among the six cases who were diagnosed as having primary orbital hemangiopericytoma, all lesions were reported as vascular tumors and featured branching "staghorn appearance" vessels. All patients, including one male and five females, presented with progressive proptosis and some associated symptoms such as extraocular motility limitation with diplopia, displacement of the globe, afferent pupillary defect, congested vessels of conjunctiva, or decreased visual acuity. On computed tomography, the orbital tumors tended to manifest as circumscribed masses with homogeneous medium-to-high enhancement with contrast studies. All six patients received surgical treatments, and four of them had additional radiotherapy. Three patients had recurrence after surgeries, and one of them had multiple metastases to lung and liver. All patients were still alive after a follow-up period of 5-10 years. CONCLUSION: Orbital hemangiopericytoma has malignant potential, which may lead to local recurrence and/or metastasis. Histopathological findings alone are insufficient to predict the behavior of this tumor. Therefore, both clinical and histopathological findings are important to evaluate the treatment outcomes. Total excision accompanied with radiotherapy is suggested and long-term follow-up is required.

Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes.

Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

Predicting Athlete Intentions for Using Sports Complexes in the Post-Pandemic Era.

In recent years, the concept of health has gradually fit into people's lives through the government's promotion. The indoor sports complex is becoming more and more popular, offering people the opportunity to engage in physical and recreational activities regardless of weather conditions. Psychological and social abundance is the key to improving happiness, and the most important thing is to treat and care for yourself. Many fitness venues have emerged to provide athletes with a wide range of choices. However, the advent of the COVID-19 pandemic, which is caused by a virus mainly transmitted through direct contact or air droplets, has had a severe impact on indoor gym users. Therefore, based on the Theory of Planned Behavior (TPB) and Health-Promoting Lifestyle (HPL), this research investigated athletes' behavioral intentions regarding sports halls and perceived risks as interfering variables. For data collection, we collected data samples from sports complexes athletes in Taiwan. A total of 263 responses were analyzed via SPSS 20.0 (IBM Corporation, New York, NY, USA) and AMOS 20.0 (IBM Corporation, New York, NY, USA) seis tests. The study's results indicate that health-promoting lifestyle cognition has a positive and significant effect on behavioral intention; athletes' attitudes, subjective norms, and perceived behavioral control significantly affects the behavioral intention of using the facilities in a sports complex. Athletes' risk perceptions have an interference effect between HPL, attitude, subjective norm, perceived behavioral control, and behavioral intentions of using the facilities in a sports complex. Sports venue managers can refer to the results of this project to develop marketing strategies and promoting.

How to improve the problem of hotel manpower shortage in the COVID-19 epidemic environment? Exploring the effectiveness of the hotel practice training system.

This study aimed to examine the role of effective employee training in the sustainable growth and corporate social responsibility of hotels during the postpandemic period. An initial respondent pool was selected using purposive sampling, and 280 questionnaires were finally obtained by snowball sampling from September 2019 to February 2020. The sample was analyzed using basic statistical tests, the Pearson correlation coefficient, and multivariate regression. We then interpreted the sample data through consultation with scholars and practitioners in hotel management. Finally, the data were analyzed using multivariate verification. The results indicated that China Binhai Hotel could not foster consistent employee enthusiasm and fulfill its corporate social responsibilities during the postpandemic period due to deficiencies in its human resources training, employee benefit, job rotation, and incentive systems. We suggest for hotels to promote corporate culture, improve the system of promotion, increase employee benefits, and adjust the workplace environment and equipment provided to employees. These will improve employee attitudes toward hotel management, improve work efficiency, increase retention, and solve the problem of personnel shortage during the postpandemic period.

Travel for survive! Identifying the antecedents of vaccine tourists' travel intention: Using a stimulus-organism-response model.

The COVID-19 global pandemic and the uneven distribution of vaccines have resulted in alternative medical tourism, vaccine tourism. The purpose of this study is to identify the antecedents of vaccine tourists' travel intention. The Stimulus-organism-response model was used as a framework to understand the relationship between risk perception (stimulus), pandemic prevention attitude (organism), decision making (organism), and travel intention (response) in vaccine tourism. An online questionnaire survey method was adopted to address the purpose of the research. Purposive and snowball sampling were used to select eligible respondents who were over 18 years old and had experience in vaccine tourism. A total of 520 online questionnaires were collected, and description analysis, confirmatory factor analysis, and structural equation modeling were utilized to analyze the collected data. The findings indicated that pandemic prevention attitude is a full mediator between risk perception and travel intention. There is a significant causal relationship between risk perception and pandemic prevention attitude and between pandemic prevention attitude and travel intention. Furthermore, tourists' travel decision-making also significantly influences their travel intention. However, the relationship between tourists' risk perception and travel decision-making has no significant effect. Vaccine tourism was created based on the COVID-19 context. Therefore, in order to avoid vaccine travel becoming an infection control breach, pandemic prevention planning and the medical quality of the destination, and the prevention policies between the countries should be completely assessed and conducted.

Malignant peripheral nerve sheath tumor of the orbit: malignant transformation from neurofibroma without neurofibromatosis.

A 52-year-old woman suffered from progressive proptosis and vision loss due to a large tumor in her right orbit. Multiple recurrences of the tumor were treated with surgical excision. The pathologic diagnosis in each recurrence was neurofibroma, and the tumor transformed to malignant peripheral nerve sheath tumor in the final pathologic diagnosis. Orbital exenteration and postoperative irradiation were applied and there has been no evidence of tumor recurrence 5 years postoperatively.

Prevalence of advanced colonic polyps in asymptomatic Chinese.

AIM: To investigate the prevalence of advanced polyps in asymptomatic Chinese and to determine the risk of proximal advanced colonic polyps in subjects with and without polyps in the distal colon. METHODS: Data were collected prospectively during colonoscopic examinations performed in 5 973 subjects as part of health evaluation at our unit from December 1997 to December 2003. Polyps were considered advanced, if they were larger than 10 mm or were tubovillous, villous or malignant. Proximal colon was defined as the splenic flexure and more proximal portions of the colon. RESULTS: Colon polyps were detected in 971 (16.3%) subjects (613 males and 358 females) with their mean age being 56.6+/-10.7 years. Advanced polyps were noted in 199 (3.3%) individuals. Subjects were sub-classified according to the location of polyps into three groups: distal (569, 58.6%), proximal (284, 29.2%), and combined proximal and distal (118, 12.2%) groups. Subjects with advanced polyps in these three groups were 95 (9.8%), 56 (5.8%), and 48 (4.9%) respectively. In the 48 subjects with advanced combined polyps, 13 advanced polyps were distributed at the distal colon, 17 at the proximal colon, and 18 at both. Eighteen colon cancers including 12 at sigmoid and 6 at ascending colon were confirmed by final pathology. The relative risk for advanced proximal polyp according to distal findings was 3.1 (95%CI: 1.3-7.4) for hyperplastic polyp, 2.7 (95%CI: 1.4-5.3) for tubular polyp and 13.5 (95%CI: 5.1-35.4) for advanced polyp as compared to that for no polyp. However, 56 (28.2%) of 199 subjects with advanced polyps had no index polyps at the distal colon and might go undetected under sigmoidoscopic screening. CONCLUSION: Although distal lesions can predict the risk of advanced proximal polyps, a substantial portion of Chinese with advanced proximal polyps is not associated with any distal sentinel lesions. These data have implications for screening policy of colon cancers in Taiwanese Chinese.

Ionic liquids promote PCR amplification of DNA.

A bicyclic imidazolium ionic liquid (4d), [b-4C-im][Br], was found to be highly effective not only for promoting PCR of GC-rich DNA by minimizing non-specific amplification, but also for facilitating PCR of normal-GC DNA under mild conditions.

Increased hyaluronan and CD44 expressions in intravenous leiomyomatosis.

BACKGROUND: To determine the influence of hyaluronan and its receptor CD44 in the angiogenesis and invasiveness of intravenous leiomyomatosis (IVL). METHODS: Paraffin-embedded sections from four IVL cases and 10 uterine leiomyoma cases were immunohistochemically stained for CD34, CD44, basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and platelet-derived growth factor and assayed for microvessel densities. Hyaluronan was immunostained by biotinylated hyaluronan-binding peptide and the results were clinically correlated. RESULTS: CD34 labeling showed significantly increased microvessel counts in IVL (156.6+/-3.7), when compared to uterine leiomyomas (61.3+/-27.3; P<0.001). Hyaluronan and its receptor CD44 were prominently expressed in IVL when compared to leiomyomas and associated with an elevation in bFGF expression. CONCLUSIONS: IVL is a highly vascular neoplasm with elevated microvessel counts. The increase of hyaluronan and CD44 expression in IVL suggests that it is highly angiogenic and has an invasive potential. Elevation of hyaluronan may play a possible role in the pathogenesis of IVL.