Nod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt ...bacterial recognition are paradoxically among the highest risk factors for Crohn’s disease, which involves an exaggerated immune response directed at intestinal bacteria. Here, we identified several abnormalities in the small-intestinal epithelium of Nod2−/− mice including inflammatory gene expression and goblet cell dysfunction, which were associated with excess interferon-γ production by intraepithelial lymphocytes and Myd88 activity. Remarkably, these abnormalities were dependent on the expansion of a common member of the intestinal microbiota Bacteroides vulgatus, which also mediated exacerbated inflammation in Nod2−/− mice upon small-intestinal injury. These results indicate that Nod2 prevents inflammatory pathologies by controlling the microbiota and support a multihit disease model involving specific gene-microbe interactions.
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•Nod2−/− mice develop inflammatory gene expression and goblet cell defects•Intestinal abnormalities are associated with an excessive immune response•Nod2−/− mice are susceptible to expansion and colonization by B. vulgatus•B. vulgatus mediates intestinal abnormalities and inflammation in Nod2−/− mice
Deficient bacterial recognition by NOD2 is associated with inflammatory bowel disease. Cadwell and colleagues demonstrate that mice deficient in Nod2 display a pathological expansion of the commensal bacterium Bacteroides vulgatus and subsequent inflammatory abnormalities in the small intestine.
Since the coronavirus disease 2019 (COVID-19) pandemic outbreak, the incidence of mental health problems in perinatal women has been high, and particularly prominent in China which was the first ...country affected by COVID-19. This paper aims to investigate the current situation and the related factors of maternal coping difficulties after discharge during COVID-19.
General information questionnaires (the Perinatal Maternal Health Literacy Scale, Postpartum Social Support Scale and Post-Discharge Coping Difficulty Scale-New Mother Form) were used to investigate 226 puerperal women in the third week of puerperium. The influencing factors were analyzed by single factor analysis, correlation and multiple linear regression.
The total score of coping difficulties after discharge was 48.92 ± 12.05. At the third week after delivery, the scores of health literacy and social support were 21.34 ± 5.18 and 47.96 ± 12.71. There were negative correlations among health literacy, social support and coping difficulties after discharge (r = -0.34, r = -0.38, P < 0.001). Primipara, family income, health literacy and social support were the main factors influencing maternal coping difficulties after discharge.
During the COVID-19 pandemic, puerperal women in a low- and middle-income city had moderate coping difficulties after discharge and were affected by many factors. To meet the different needs of parturients and improve their psychological coping ability, medical staff should perform adequate assessment of social resources relevant to parturients and their families when they are discharged, so they can smoothly adapt to the role of mothers.
Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
An efficient and mild zinc-mediated decarboxylative alkylation of gem-difluoroalkenes with N-hydroxyphthalimide (NHP) esters, to give monofluoroalkenes in moderate to excellent yields with high ...Z-selectivity is reported. The reaction tolerates a broad range of functional groups and can be easily scaled up, which thus may pave the way for its further applications in medicinal chemistry and materials science.
Purpose
This paper aims to examine the role of extraversion and agreeableness personality traits on Generation Y (Gen Y) consumers’ attitudes toward and willingness to pay for green hotels. Gen Y is ...a large and influential generational group, with a significant interest in green issues. There has been a lack of research on the consumer decision-making process toward green hotels. Specifically, the impact of personality on green attitudes and behavioral intentions is rarely investigated.
Design/methodology/approach
A major survey consisting of 406 final respondents was conducted. The 29-item survey questionnaire comprises items for extraversion, agreeableness, attitudes toward green hotels and behavioral intention toward green hotels. Numerous statistical techniques, including structural equation modeling, were used to evaluate the data collected.
Findings
The results show that extraversion and agreeableness personality traits are positively associated with respondents’ attitudes toward green hotels. Stronger and more positive attitudes toward green hotels lead to greater willingness to pay for green hotels. Moreover, attitudes toward green hotels mediate the relationship between the two personality traits and willingness to pay. These findings of Gen Y subsegments can be useful to hotel managers in identifying who are more likely to stay in and pay for environmentally friendly hotels.
Originality/value
Gen Ys are an influential consumer age group in the service industry, and their general attitudes toward “green” products are important to modern hoteliers. However, few researchers have examined Gen Ys’ attitudes and behavioral intentions toward green issues. No research has examined the role of personality traits on consumers’ perceptions of green hotels. The present study found that the extraversion and agreeableness traits of Gen Y individuals are linked to their attitudes toward and willingness to pay for green hotels.
Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth ...colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.
Resistance to chemotherapy represents a major cause for treatment failure in multiple myeloma (MM). Herein, this study was conducted to explore the effect of SDF‐1/CXCR4 and interleukin‐6 (IL‐6) in ...MM cell adhesion‐mediated chemoresistance. Enzyme‐linked immunosorbent assay was applied to detect expressions of SDF‐1α and IL‐6 in MM patients and healthy controls. RPMI‐8226 cells and isolated bone marrow stromal cells (BMSCs) were stimulated using recombinant SDF‐1α and IL‐6. Effect of cocultured BMSCs and RPMI‐8226 cells on chemosensitivity and apoptosis of RPMI‐8226 cells was analyzed. Effect of doxorubicin on the adhesion rate of RPMl‐8226 cells to BMSCs was analyzed by calcitonin test. Effect of SDF‐1α‐induced upregulation of IL‐6 on chemotherapeutic resistance and apoptosis of RPMI‐8226 cells in adhesion state was analyzed. Cell adhesion model was treated with recombinant protein SDF‐1α and phosphoinositide 3‐kinase (P13K) inhibitor Wortmarmin. The levels of P13K and protein kinase B (AKT) and its phosphorylation as well as the expression of IL‐6 were analyzed. SDF‐1α was positively correlated with IL‐6. Recombinant human SDF‐1α increased IL‐6 expression and induced IL‐6 secretion in a time‐ and dose‐dependent manner in BMSCs, which was inhibited by IL‐6 and SDF‐1α neutralizing antibodies. Coculture of MM cells with BMSCs increased the drug resistance and inhibited the apoptosis on MM cells. SDF‐1α‐induced IL‐6 upregulation mediates chemoresistance and apoptosis of RPMI‐8226 cells in adhesion state. SDF‐1α may up‐regulate the expression of IL‐6 by activating the P13K/AKT signaling pathway. SDF‐1/CXCR4 may up‐regulate the expression of IL‐6 through the activation of the P13K/AKT signaling pathway, thereby affecting the chemoresistance mediated by adhesion in MM cells.
Evidence suggests that PD-L1 can be induced with radiotherapy and may be an immune escape mechanism in cancer. Monitoring this response is limited, as repetitive biopsies during therapy are ...impractical, dangerous, and miss tumor stromal cells. Monitoring PD-L1 expression in both circulating tumor cells (CTCs) and circulating stromal cells (CStCs) in blood-based biopsies might be a practical alternative for sequential, noninvasive assessment of changes in tumor and stromal cells.
Peripheral blood was collected before and after radiotherapy from 41 patients with lung cancer, as were primary biopsies. We evaluated the expression of PD-L1 and formation of RAD50 foci in CTCs and a CStC subtype, cancer-associated macrophage-like cells (CAMLs), in response to DNA damage caused by radiotherapy at the tumor site.
Only 24% of primary biopsies had sufficient tissue for PD-L1 testing, tested with IHC clones 22c3 and 28-8. A CTC or CAML was detectable in 93% and 100% of samples, prior to and after radiotherapy, respectively. RAD50 foci significantly increased in CTCs (>7×,
< 0.001) and CAMLs (>10×,
= 0.001) after radiotherapy, confirming their origin from the radiated site. PD-L1 expression increased overall, 1.6× in CTCs (
= 0.021) and 1.8× in CAMLs (
= 0.004): however, individual patient PD-L1 expression varied, consistently low/negative (51%), consistently high (17%), or induced (31%).
These data suggest that RAD50 foci formation in CTCs and CAMLs may be used to track cells subjected to radiation occurring at primary tumors, and following PD-L1 expression in circulating cells may be used as a surrogate for tracking adaptive changes in immunotherapeutic targets.
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Abstract
Background
In the United States, liver cancer is the fifth and seventh most common cause of cancer-related death among men and women, respectively. Compared with other racial or ethnic ...groups in the United States, Asian and Pacific Islander populations experience the highest incidence rates of liver cancer, but little is known about disparities in risk of advanced-stage disease or risk of liver cancer mortality across these heterogenous populations.
Methods
In a population-based cohort of 60 146 patients aged 20-79 years diagnosed with liver cancer from 2004 to 2018 identified through the Surveillance, Epidemiology, and End Results Program, we examined associations between race or ethnicity, including specific Asian and Pacific Islander subgroups, and risk of advanced-stage liver cancer and liver cancer–specific mortality.
Results
Compared with non-Hispanic White patients, non-Hispanic Black, Filipino, and Laotian patients had 30%-85% elevated odds of being diagnosed with stage IV liver cancer, whereas Hispanic, Vietnamese, and Chinese patients had 7%-33% lower odds of being diagnosed with stage IV liver cancer (all P <.05). Additionally, non-Hispanic Black, Kampuchean, and Laotian patients had 6%-22% elevated hazards of liver cancer–specific mortality, and Hispanic, Vietnamese, Chinese, and Korean patients had 3%-27% lower hazards of liver cancer–specific mortality (all P <.05). All statistical tests were 2-sided.
Conclusions
Substantial variations in risk of advanced-stage liver cancer and risk of liver cancer mortality were observed by race and ethnicity, including considerable heterogeneity across individuals broadly defined as Asians and Pacific Islanders. Further efforts to understand the contributors to these disparities are needed to inform potential targeted screening and treatment interventions.
CCR5 is a motility chemokine receptor implicated in tumor progression, whose activation and subsequent endocytosis may identify highly aggressive breast cancer cell subtypes likely to spread into the ...circulatory system.
The MDA-MB-231 cell line was used to model and visualize CCR5 activation by stimulation with RANTES, in an effort to quantify CCR5 endocytosis from the cell surface to the perinuclear space. CCR5 expression was then examined in tumor-associated cells (TACs), consisting of circulating tumor cells and circulating stromal cells, isolated from the peripheral blood of 54 metastatic breast cancer (mBC) patients to evaluate these CCR5 pooling patterns as they relate to progression and survival over 2 years.
In MB231 experiments, it was observed that CCR5 formed ~ 1 micron clusters identified as "CCR5 pools" on the surface of the cell, which in the presence of RANTES were endocytosed and translocated to the cell cytoplasm. When TACs from patients were analyzed, CCR5 pools were observed on the cell surface and translocating to the nuclear area, with CCR5 also having a positive statistical correlation between increased numbers of TACs and increased CCR5 pools on the cells. Further, it was determined that patients with very high numbers of CCR5 (> 10 CCR5 pools), specifically in the circulating stromal cells, were associated with worse progression-free survival (hazard ratio = 4.5, p = 0.002) and worse overall survival (hazard ratio = 3.7, p = 0.014).
Using a liquid biopsy approach, we evaluated two populations of tumor-associated cells emanating from primary tumors, with data suggesting that upregulation of the motility chemokine CCR5 in TACs provides clinically relevant opportunities for treating and tracking drug targetable receptors in mBC.
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