Protective Effect and Mechanisms of Eckol on Chronic Ulcerative Colitis Induced by Dextran Sulfate Sodium in Mice.

The use of functional foods and their bioactive components is receiving increasing attention as a complementary and alternative therapy for chronic ulcerative colitis (UC). This study explored the protective effect and mechanisms of Eckol, a seaweed-derived bioactive phlorotannin, on the dextran sodium sulfate (DSS)-induced chronic UC in mice. Eckol (0.5-1.0 mg/kg) reduced DSS-enhanced disease activity indexes, and alleviated the shortening of colon length and colonic tissue damage in chronic UC mice. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were significantly decreased, and the level of anti-inflammatory IL-10 was enhanced in the serum and colonic tissues collected from Eckol-treated mice compared with the DSS controls. Eckol administration significantly reduced the number of apoptotic cells and the expression of cleaved Caspase-3, and increased the B-cell lymphoma-2 (Bcl-2)/B-cell lymphoma-2- associated X (Bax) ratio in DSS-challenged colons. There were more cluster of differentiation (CD)11c+ dendritic cells and CD8+ T cells, and less CD4+ T cells infiltrated to inflamed colonic tissues in the Eckol-treated groups. Expression of colonic Toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) p65, phosphorylated-signal transducer and activator of transcription (pSTAT)3 was significantly down-regulated by Eckol compared with the DSS-challenged group. In conclusion, our data suggest that Eckol appeared to be a potential functional food ingredient for protection against chronic UC. The anti-colitis mechanisms of Eckol might be attributed to the down-regulation of the TLR4/NF-κB/STAT3 pathway, inhibition of inflammation and apoptosis, as well as its immunoregulatory activity.

Risks of benzalkonium chlorides as emerging contaminants in the environment and possible control strategies from the perspective of ecopharmacovigilance.

An unprecedented increase in the use of disinfection products triggered by the coronavirus disease 2019 (COVID-19) pandemic is resulting in aggravating environmental loads of disinfectants as emerging contaminants, which has been considered a cause for worldwide secondary disasters. This review analyzed the literature published in the last decade about occurrence, bioaccumulation, and possible environmental risks of benzalkonium chlorides (BKCs) as emerging contaminants. Results indicated that BKCs globally occurred in municipal wastewater, surface water, groundwater, reclaimed water, sludge, sediment, soil, roof runoff, and residential dust samples across 13 countries. The maximum residual levels of 30 mg/L and 421 µg/g were reported in water and solid environmental samples, respectively. Emerging evidences suggested possible bioaccumulation of BKCs in plants, even perhaps humans. Environmentally relevant concentrations of BKCs exert potential adverse impacts on aquatic and terrestrial species, including genotoxicity, respiratory toxicity, behavioural effects and neurotoxicity, endocrine disruption and reproductive impairment, phytotoxicity, etc. Given the intrinsic biocidal and preservative properties of disinfectants, the inductive effects of residual BKCs in environment in terms of resistance and imbalance of microorganisms have been paid special attention. Considering the similarities of disinfectants to pharmaceuticals, from the perspective of ecopharmacovigilance (EPV), a well-established strategy for pharmaceutical emerging contaminants, we use the control of BKC pollution as a case, and provide some recommendations for employing the EPV measures to manage environmental risks posed by disinfectant emerging contaminants.

TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155.

Ulcerative colitis (UC) has closely been associated with an increased risk of colorectal cancer. However, the exact mechanisms underlying colitis-associated cancer (CAC) development remain unclear. As a classic pattern-recognition receptor, Toll like receptor (TLR)4 is a canonical receptor for lipopolysaccharide of Gram-negative bacteria (including two CAC-associated pathogens Fusobacterium nucleatum and Salmonella), and functions as a key bridge molecule linking oncogenic infection to colonic inflammatory and malignant processes. Accumulating studies verified the overexpression of TLR4 in colitis and CAC, and the over-expressed TLR4 might promote colitis-associated tumorigenesis via facilitating cell proliferation, protecting malignant cells against apoptosis, accelerating invasion and metastasis, as well as contributing to the creation of tumor-favouring cellular microenvironment. In recent years, considerable attention has been focused on the regulation of TLR4 signaling in the context of colitis-associated tumorigenesis. MicroRNA (miR)-155 and TLR4 exhibited a similar dynamic expression change during CAC development and shared similar CAC-promoting properties. The available data demonstrated an interplay between TLR4 and miR-155 in the context of different disorders or cell lines. miR-155 could augment TLR4 signaling through targeting negative regulators SOCS1 and SHIP1; and TLR4 activation would induce miR-155 expression via transcriptional and post-transcriptional mechanisms. This possible TLR4-miR-155 positive feedback loop might result in the synergistic accelerating effect of TLR4 and miR-155 on CAC development. Video abstract.

Associations between metal(loid) exposure with overweight and obesity and abdominal obesity in the general population: A cross-sectional study in China.

Previous studies have revealed links between metal(loid)s and health problems; however, the link between metal(loid)s and obesity remains controversial. We evaluated the cross-sectional association between metal(loid) exposure in whole blood and obesity among the general population. Vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), thallium (T1), and lead (Pb) were measured in 3029 subjects in Guangdong Province (China) using ICP-MS. The prevalence of overweight and obesity (OWO) and abdominal obesity (AOB) was calculated according to body mass index (BMI) and waist circumference (WC), respectively. Multivariate analysis showed that elevated blood Cu, Cd, and Pb levels were inversely associated with the risk of OWO, and these associations were confirmed by a linear dose-response relationship. Elevated blood Co concentration was associated with a decreased risk of AOB. A quantile g-computation approach showed a significantly negative mixture-effect of 13 metal(loid)s on OWO (OR: 0.96; 95% CI: 0.92, 0.99). Two metals-Ni and Mo-were inversely associated with the risk of OWO but positively associated with AOB. We cross-grouped the two obesity measurement types and found that the extremes of metal content were present in people with AOB only. In conclusion, blood Cu, Mo, Ni, Cd, and Pb were inversely associated with the risk of OWO. The presence of blood Co may be protective, while Ni and Mo exposure might increase the risk of AOB. The association between metal(loid) exposure and obesity warrants further investigation in longitudinal cohort studies.

Attitudes and opinions about ecopharmacovigilance from multi-disciplinary perspectives: a cross-sectional survey among academic researchers in China.

As a promising upstream strategy to reduce the environmental loads of pharmaceutical emerging contaminants (PECs) through source control, ecopharmacovigilance (EPV) is concerned with the set of activities to identify, evaluate, understand, and prevent against diverse PEC-related problems, and has been accepted as a multi-disciplinary and multi-stakeholder system. This cross-sectional observational survey aimed to assess the attitudes and opinions about EPV from multi-disciplinary perspectives among Chinese academic professors from four main EPV-related disciplines including pharmacy, management, clinical medicine, and environmental and ecological science based on a self-developed questionnaire. Forty-two usable survey instruments were acquired. Results showed that the responding Chinese academic researchers from different disciplines expressed consistently positive attitudes and strong intentions for EPV, in spite of several disparities existing among disciplinary groups showing that pharmacy and medical researchers felt more certain of the environmental adverse effects of PECs, and researchers in pharmacy and environmental and ecological science were more interested in EPV. A multi-disciplinary consensus was achieved in regard to the types of key stakeholders in EPV practices including the pharmaceutical manufacturers, the public, the drug safety authority, hospitals, and the environmental protection agency. The main roles and responsibilities of each stakeholder identity in EPV practices were summarized based on the expert opinions.

Vaccination practices, knowledge and attitudes regarding COVID-19 vaccines among Chinese university students: a cross-sectional study from a comprehensive university in Wuhan.

OBJECTIVE: In China, a free national COVID-19 vaccination programme has been launched in spring 2021 and is ongoing across the country. This study aimed to preliminarily understand the current COVID-19 vaccination practices and the associated knowledge/attitude factors among Chinese university students. DESIGN AND SETTING: A single-centre cross-sectional questionnaire-based study was conducted between 1 and 20 May 2021 among a convenience sample of Chinese university students recruited from a comprehensive university in Wuhan. A total of 359 valid questionnaires were obtained. RESULTS: Just 1 month after the commencement of the university vaccination process, 75% of responding students had received the COVID-19 vaccination. Students without experience of COVID-19 infection were more likely to get vaccinated than those who had been infected. Most (57%) received information about COVID-19 vaccination through official announcements released by the university, and 67% were vaccinated at vaccination place arranged by the university. An interesting finding is that, although the overall vaccine uptake rate was 75%, nearly one-third of vaccinees did not know or incorrectly stated the type of COVID-19 vaccines that they had received. Mean knowledge test score was 3.05 out of 6, suggesting poor knowledge regarding COVID-19 vaccines. The vaccinated showed more positive attitudes towards the importance of establishing herd immunity through the COVID-19 vaccination programme for pandemic control than the non-vaccinated did. 'Effectiveness in preventing COVID-19' was perceived by 76% respondents as the most important factor contributing to COVID-19 vaccination. A total of 76% were worried about safety-related issues, including 'unknown long-term safety', 'vaccine allergy' and 'vaccine-caused COVID-19 infection'. CONCLUSIONS: Data suggested a rapid and effective progress of the national COVID-19 vaccination programme in China among university students. Taking effective official actions, as well as enhancing the belief in vaccines' effectiveness, might be necessary for the good implementation of COVID-19 vaccination programmes.

Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression.

As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.

Impact of the COVID-19 pandemic on household disinfectant consumption behaviors and related environmental concerns: A questionnaire-based survey in China.

Considering the potential hazardous effects of disinfectant residues on environment, organisms and biodiversity, the sharp rise in use of disinfectants during COVID-19 pandemic has been considered highly likely to cause worldwide secondary disasters in ecosystems and human health. This questionnaire-based survey investigated the impact of COVID-19 outbreak on household disinfectant product consumption levels and behavior of 3667 Chinese residents. In particular, in the context that no strategy is currently available to minimize the disinfectant pollution, based on the similarities between disinfectants and pharmaceuticals, we proposed a perspective of ecopharmacovigilance (EPV), which is an effective measure to minimize the environmental risks posed by pharmaceuticals using drug administration protocols, for disinfectant environmental risk management. The public's environmental perceptions, attitudes and the related practices regarding household disinfectant consumption from an EPV perspective were also included in the study. The results showed that the COVID-19 outbreak caused a tremendous rise in the public's household disinfectant consumption and usage levels in China. After the COVID-19 outbreak, the chlorine-based and alcohol-based disinfectants were considered as the most preferred products for household disinfection and hand sanitization, respectively. Importantly, the Chinese public's environmental perceptions and practice on disinfectants were poor. Less than half respondents had positive attitudes toward the source control of disinfectant pollution. The population groups including females, the middle aged adults, those having healthcare professional background, as well as the higher-educated could be focused on to develop targeted efforts for the future control of disinfectant pollution in environment.