Hypoxia-inducible factor 3α1 increases epithelial-to-mesenchymal transition and iron uptake to drive colorectal cancer liver metastasis.

BACKGROUND/OBJECTIVES: Hypoxia-inducible factor (HIF)-3α1's role in colorectal cancer (CRC) cells, especially its effects on epithelial-mesenchymal transition (EMT), zinc finger E-box binding homeobox 2 (ZEB2) gene expression, and iron metabolism, remains largely unstudied. This research sought to elucidate these relationships. METHODS: RNA-seq was conducted to investigate the impact of HIF-3α1 overexpression in CRC cells. Dual-luciferase reporter assays assessed the direct targeting of ZEB2 by HIF-3α1. Scratch assays measured changes in cell migration following HIF-3α1 overexpression and ZEB2 knockdown. The effects of HIF-3α1 overexpression on colon tumour growth and liver metastasis were examined in vivo. Iron chelation was used to explore the role of iron metabolism in HIF-3α1-mediated EMT and tumour growth. RESULTS: HIF-3α1 overexpression induced EMT and upregulated ZEB2 expression, enhancing cancer cell migration. ZEB2 knockdown reduced mesenchymal markers and cell migration. HIF-3α1 promoted colon tumour growth and liver metastasis, increased transferrin receptor (TFRC) expression and cellular iron levels, and downregulated HIF-1α, HIF-2α, and NDRG1. Iron chelation mitigated HIF-3α1-mediated EMT, tumour growth, and survival. CONCLUSIONS: HIF-3α1 plays a critical role in colon cancer progression by promoting EMT, iron accumulation, and metastasis through ZEB2 and TFRC regulation, suggesting potential therapeutic targets in CRC.

Oct4 activates IL-17A to orchestrate M2 macrophage polarization and cervical cancer metastasis.

BACKGROUND: Cervical cancer is a common malignant tumor in the female. Interleukin (IL)-17A is a proinflammatory factor and exerts a vital function in inflammatory diseases and cancers. M2 macrophage has been confirmed to promote tumor development. Nevertheless, it is not yet known whether IL-17A facilitates cervical cancer development by inducing M2 macrophage polarization. Therefore, this study was conducted to investigate the regulatory effect of IL-17A on M2 macrophage polarization and the underlying mechanism in cervical cancer development. METHODS: RT-qPCR was utilized for testing IL-17A expression in cancer tissues and cells. Flow cytometry was applied to evaluate the M1 or M2 macrophage polarization. Cell proliferative, migratory, and invasive capabilities were measured through colony formation and transwell assays. ChIP and luciferase reporter assays were applied to determine the interaction between IL-17A and octamer-binding transcription factor 4 (OCT4). RESULTS: IL-17A expression and concentration were high in metastatic tissues and cells of cervical cancer. IL-17A was found to facilitate M2 macrophage polarization in cervical cancer. Furthermore, IL-17A facilitated the macrophage-mediated promotion of cervical cancer cell proliferative, migratory, and invasive capabilities. Mechanistic assays manifested that Oct4 binds to and transcriptionally activated IL-17A in cervical cancer cells. Furthermore, Oct4 promoted cervical cancer cell malignant phenotype and M2 macrophage polarization by activating the p38 pathway that, in turn, upregulated IL-17A. Additionally, in vivo experiments confirmed that Oct4 knockdown reduced tumor growth and metastasis. CONCLUSION: Oct4 triggers IL-17A to facilitate the polarization of M2 macrophages, which promotes cervical cancer cell metastasis.

Exosomes from senescent epithelial cells activate pulmonary fibroblasts via the miR-217-5p/Sirt1 axis in paraquat-induced pulmonary fibrosis.

BACKGROUND: Paraquat (PQ) is a widely used and highly toxic herbicide that poses a significant risk to human health. The main consequence of PQ poisoning is pulmonary fibrosis, which can result in respiratory failure and potentially death. Our research aims to uncover a crucial mechanism in which PQ poisoning induces senescence in epithelial cells, ultimately regulating the activation of pulmonary fibroblasts through the exosomal pathway. METHODS: Cellular senescence was determined by immunohistochemistry and SA-ß-Gal staining. The expression of miRNAs was measured by qPCR. Pulmonary fibroblasts treated with specific siRNA of SIRT1 or LV-SIRT1 were used to analysis senescent exosomes-mediated fibroblasts activation. Luciferase reporter assay and western blot were performed to elucidated the underlying molecular mechanisms. The effects of miR-217-5p antagomir on pulmonary fibrosis were assessed in PQ-poisoned mice models. RESULTS: Impairing the secretion of exosomes effectively mitigates the harmful effects of senescent epithelial cells on pulmonary fibroblasts, offering protection against PQ-induced pulmonary fibrosis in mice. Additionally, we have identified a remarkable elevation of miR-217-5p expression in the exosomes of PQ-treated epithelial cells, which specifically contributes to fibroblasts activation via targeted inhibition of SIRT1, a protein involved in cellular stress response. Remarkably, suppression of miR-217-5p effectively impaired senescent epithelial cells-induced fibroblasts activation. Further investigation has revealed that miR-217-5p attenuated SIRT1 expression and subsequently resulted in enhanced acetylation of ß-catenin and Wnt signaling activation. CONCLUSION: These findings highlight a potential strategy for the treatment of pulmonary fibrosis induced by PQ poisoning. Disrupting the communication between senescent epithelial cells and pulmonary fibroblasts, particularly by targeting the miR-217-5p/SIRT1/ß-catenin axis, may be able to alleviate the effects of PQ poisoning on the lungs.

Effect of marital status on the survival outcomes of cervical cancer: a retrospective cohort study based on SEER database.

BACKGROUND: Cervical cancer is the fourth most common malignant tumor troubling women worldwide. Whether marital status affects the prognosis of cervical cancer is still unclear. Here, we investigate the prognostic value of marital status in patients with cervical cancer based on the seer database. MATERIAL/METHODS: The demographic and clinical data of patients with cervical cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. Patients were divided into two groups (married and unmarried) according to marital status, and then the clinical characteristics of each group were compared using the chi-square test. Propensity score matching (PSM) was used to reduce differences in baseline characteristics. The overall survival (OS) and cervical cancer-specific survival (CCSS) were assessed by the Kaplan-Meier method, univariate and multivariate Cox regression models, and stratified analysis. Moreover, univariate and multivariate competing risk regression models were performed to calculate hazard ratios (HR) of death risk. RESULTS: A total of 21,148 patients were included in this study, including 10,603 married patients and 10,545 unmarried patients. Married patients had better OS(P < 0.05) and CCSS (P < 0.05) compared to unmarried patients, and marital status was an independent prognostic factor for both OS (HR: 0.830, 95% CI: 0.798-0.862) and CCSS (HR: 0.892, 95% CI: 0.850-0.937). Moreover, after eliminating the competing risk, married patients (CCSD: HR:0.723, 95% CI: 0.683-0.765, P < 0.001) had a significantly decreased risk of death compared to unmarried patients. In stratified analysis, the married patients showed better OS and CCSS than the unmarried patients diagnosed in 1975-2000 and 2001-2017. CONCLUSIONS: Being married was associated with a favorable prognosis of cervical cancer, and marital status was an independent prognostic factor for cervical cancer.

Preliminary clinical study of personalized neoantigen vaccine therapy for microsatellite stability (MSS)-advanced colorectal cancer.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis.

Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining.

MmuPV1 is a useful model for studying papillomavirus-induced tumorigenesis. We used RNA-seq to look for chimeric RNAs that map to both MmuPV1 and host genomes. In tumor tissues, a higher proportion of total viral reads were virus-host chimeric junction reads (CJRs) (1.9‰ - 7‰) than in tumor-free tissues (0.6‰ - 1.3‰): most CJRs mapped to the viral E2/E4 region. Although most of the MmuPV1 integration sites were mapped to intergenic regions and introns throughout the mouse genome, integrations were seen more than once in several genes: Malat1, Krt1, Krt10, Fabp5, Pard3, and Grip1; these data were confirmed by rapid amplification of cDNA ends (RACE)-Single Molecule Real-Time (SMRT)-seq or targeted DNA-seq. Microhomology sequences were frequently seen at host-virus DNA junctions. MmuPV1 infection and integration affected the expression of host genes. We found that factors for DNA double-stranded break repair and microhomology-mediated end-joining (MMEJ), such as H2ax, Fen1, DNA polymerase Polθ, Cdk1, and Plk1, exhibited a step-wise increase and Mdc1 a decrease in expression in MmuPV1-infected tissues and MmuPV1 tumors relative to normal tissues. Increased expression of mitotic kinases CDK1 and PLK1 appears to be correlated with CtIP phosphorylation in MmuPV1 tumors, suggesting a role for MMEJ-mediated DNA joining in the MmuPV1 integration events that are associated with MmuPV1-induced progression of tumors.

Fine mapping and candidate gene analysis of qSB12YSB, a gene conferring major quantitative resistance to rice sheath blight.

KEY MESSAGE: qSB12YSB, a major quantitative sheath blight resistance gene originated from rice variety YSBR1 with good breeding potential, was mapped to a 289-Kb region on chromosome 12. Sheath blight (ShB), caused by Rhizoctonia solani kühn, is one of the most serious global rice diseases. Rice resistance to ShB is a typical of quantitative trait controlled by multiple quantitative trait loci (QTLs). Many QTLs for ShB resistance have been reported while only few of them were fine-mapped. In this study, we identified a QTL on chromosome 12, in which the qSB12YSB resistant allele shows significant ShB resistance, by using 150 BC4 backcross inbred lines employing the resistant rice variety YSBR1 as the donor and the susceptible variety Lemont (LE) as the recurrent parent. We further fine-mapped qSB12YSB to a 289-kb region by generating 34 chromosomal segment substitution lines and identified a total of 18 annotated genes as the most likely candidates for qSB12YSB after analyzing resequencing and transcriptomic data. KEGG analysis suggested that qSB12YSB might activate secondary metabolites biosynthesis and ROS scavenging system to improve ShB resistance. qSB12YSB conferred significantly stable resistance in three commercial rice cultivars (NJ9108, NJ5055 and NJ44) in field trials when introduced through marker assisted selection. Under severe ShB disease conditions, qSB12YSB significantly reduced yield losses by up to 13.5% in the LE background, indicating its great breeding potential. Our results will accelerate the isolation of qSB12YSB and its utilization in rice breeding programs against ShB.

Relationship between sleep disorders and female infertility among US reproductive-aged women.

PURPOSE: Sleep disorders are a risk factor for a wide variety of dysfunctions of endocrine, metabolic, cardiovascular, and neurological diseases. However, the risk of sleep disorders to female infertility has not been thoroughly explored. Our study aimed to examine whether or not sleep disorders increase the risk of female infertility. METHODS: Cross-sectional data on sleep disorders and fertility history were obtained from the National Health and Nutrition Examination Survey 2013-2018. Women aged 20 to 40 years old were enrolled in our study. Weighted multivariable logistic regression models and stratified analysis by age, smokers, and patient health questionnaire-9 (PHQ-9) score were conducted to estimate the effect of sleep disorders on female infertility. RESULT: Among 1820 reproductive-age females, 248 individuals had infertility and 430 individuals had sleep disorders. Two weighted logistic regression models found that sleep disorders were an independent risk factor for infertility. After adjusting for the covariates (age, race/ethnicity, marital status, education level, poverty income ratio, body mass index (BMI), waist circumference, PHQ-9 score, smokers, drinkers, and sleeping hours), the risk of infertility was 2.14-fold higher in individuals with sleep disorders than in those without. The further stratified analysis demonstrated that the relationship between sleep disorders and infertility was maintained and that the risk was higher particularly in infertile women aged 40-44 years, with PHQ-9 score greater than 10, and smokers. CONCLUSION: A strong association was found between sleep disorders and female infertility, and the association remained after adjusting for other confounding factors.

Erythropoietin inhibits neutrophil extracellular traps formation to ameliorate lung injury in a pneumonia model.

BACKGROUND: Severe pneumonia is a kind of disease that develops from lung inflammation, and new drugs are still required to treat the same. Erythropoietin (EPO) is widely used to treat anemia in patients. However, there are fewer studies on the role of EPO in neutrophil extracellular trappings (NETs) and pneumonia, and the mechanism is unclear. OBJECTIVE: To investigate the possible effects of EPO on the formation of NETs and progression of pneumonia. METHODS: Mice pneumonia model was induced by tracheal lipopolysaccharide (LPS) administration. Hematoxylin and eosin (H&E) staining and automatic blood cell analysis were performed in this model to confirm the effects of EPO on lung injury. Flow cytometry, enzyme-linked immunosorbent serological assay, and immunostaining assay were conducted to detect the effects of EPO on the inflammation as well as formation of NETs in mice. Immunoblot was further conducted to confirm the mechanism. RESULTS: EPO alleviated LPS-induced lung injury. EPO reduced the release of inflammatory factors induced by LPS. In addition, EPO inhibited the formation of NETs. Mechanically, EPO inhibited tumor necrosis factor (TNF) receptor associated factor 2 (TRAF2)/nuclear factor kappa-B (NF-κB) activity in mouse models, and therefore suppressed the progression of pneumonia. CONCLUSION: EPO inhibited formation of NETs to ameliorate lung injury in a pneumonia model, and could serve as a drug of pneumonia.

Use of a two-handed model to improve comprehension of ventricular outflow tract anatomy.

BACKGROUND: Mastering cardiac anatomy is a formidable obstacle in the learning process for cardiac electrophysiology trainees. The complex three-dimensional characteristics and contiguous relationship of the ventricular outflow tract are particularly difficult to visualize with the limited study methods available. The hands can recreate a morphology similar to the ventricular outflow tract; this study explored whether a two-handed model of the heart helps electrophysiology trainees improve their understanding of ventricular outflow tract anatomy. METHODS: After an initial assessment, trainees were randomly placed into variable and control groups. Subsequently, all trainees learned the outflow tract anatomy using routine methods, with the variable group receiving additional instruction using the two-handed model. One day and one week after the course conclusion, knowledge of the ventricular outflow tract anatomy was assessed for the participants in both groups. RESULTS: Thirty-eight trainees participated (19 in each group). The median scores obtained for the first, second, and third tests were 38 (24,55), 80 (70,86), and 75 (70,81) points, respectively. In the second test, trainees in the variable group had a mean score 6.8 points higher than those in the control group (p = 0.103); in the last test, the mean score was 9.7 points higher in the variable group than in the control group (p = 0.003). CONCLUSIONS: It is convenient to use hands to create a model representing the ventricular outflow tract. Trainees using this model had a better understanding and retention of the ventricular outflow tract anatomy compared to those of the control group.

Can cognition help predict suicide risk in patients with major depressive disorder? A machine learning study.

BACKGROUND: Previous studies suggest that deficits in cognition may increase the risk of suicide. Our study aims to develop a machine learning (ML) algorithm-based suicide risk prediction model using cognition in patients with major depressive disorder (MDD). METHODS: Participants comprised 52 depressed suicide attempters (DSA) and 61 depressed non-suicide attempters (DNS), and 98 healthy controls (HC). All participants were required to complete a series of questionnaires, the Suicide Stroop Task (SST) and the Iowa Gambling Task (IGT). The performance in IGT was analyzed using repeated measures ANOVA. ML with extreme gradient boosting (XGBoost) classification algorithm and locally explanatory techniques assessed performance and relative importance of characteristics for predicting suicide attempts. Prediction performances were compared with the area under the curve (AUC), decision curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: DSA and DNS preferred to select the card from disadvantageous decks (decks "A" + "B") under risky situation (p = 0.023) and showed a significantly poorer learning effect during the IGT (F = 2.331, p = 0.019) compared with HC. Performance of XGBoost model based on demographic and clinical characteristics was compared with that of the model created after adding cognition data (AUC, 0.779 vs. 0.819, p > 0.05). The net benefit of model was improved and cognition resulted in continuous reclassification improvement with NRI of 5.3%. Several clinical dimensions were significant predictors in the XGBoost classification algorithm. LIMITATIONS: A limited sample size and failure to include sufficient suicide risk factors in the predictive model. CONCLUSION: This study demonstrate that cognitive deficits may serve as an important risk factor to predict suicide attempts in patients with MDD. Combined with other demographic characteristics and attributes drawn from clinical questionnaires, cognitive function can improve the predictive effectiveness of the ML model. Additionally, explanatory ML models can help clinicians detect specific risk factors for each suicide attempter within MDD patients. These findings may be helpful for clinicians to detect those at high risk of suicide attempts quickly and accurately, and help them make proactive treatment decisions.

Ginsenoside Rg1 suppresses paraquat-induced epithelial cell senescence by enhancing autophagy in an ATG12-dependent manner.

Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ-induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ-poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ-induced pulmonary fibrosis and the underlying mechanism. In vivo, the treatment of Rg1 can attenuate PQ-induced pulmonary fibrosis and decrease senescence and senescence associated secretory phenotype (SASP) expression. In vitro, Rg1 can effectively eliminate senescent cells via apoptosis, but not normal cells. In addition, we demonstrate that Rg1 can enhance autophagy activity via inducing the expression of ATG12. Inhibition of autophagy via 3-MA or transfection of the siRNA targeting ATG12 can impair the antiaging effect of Rg1. Taken together, our data implicates that Rg1 can protect pulmonary epithelial cells from PQ-induced cellular senescence in an ATG12 dependent manner, which may provide a preventive and therapeutic strategy for PQ poisoning-induced pulmonary fibrosis.

Norepinephrine induces growth of Desulfovibrio vulgaris in an iron dependent manner.

Desulfovibrio spp. is a commensal sulfate reducing bacterium that is present in small numbers in the gastrointestinal tract. Increased concentrations of Desulfovibrio spp. (blooms) have been reported in patients with inflammatory bowel disease and irritable bowel syndrome. Since stress has been reported to exacerbate symptoms of these chronic diseases, this study examined whether the stress catecholamine norepinephrine (NE) promotes Desulfovibrio growth. Norepinephrine-stimulated growth has been reported in other bacterial taxa, and this effect may depend on the availability of the micronutrient iron. OBJECTIVES: This study tested whether norepinephrine exposure affects the in vitro growth of Desulfovibrio vulgaris in an iron dependent manner. METHODS: DSV was incubated in a growth medium with and without 1 µm of norepinephrine. An additional growth assay added the iron chelator deferoxamine in NE exposed DSV. Iron regulatory genes were assessed with and without the treatment of NE and Deferoxamine. RESULTS: We found that norepinephrine significantly increased growth of D. vulgaris. Norepinephrine also increased bacterial production of hydrogen sulfide. Additionally, norepinephrine significantly increased bacterial expression in three of the four tested iron regulatory genes. The iron chelator deferoxamine inhibited growth of D. vulgaris in a dose-dependent manner and reversed the effect of norepinephrine on proliferation of D. vulgaris and on bacterial expression of iron regulatory genes. CONCLUSION: The data presented in this work suggests that promotion of D. vulgaris growth by norepinephrine is iron dependent.

Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman's Syndrome.

Asherman's Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated ß-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b+CD146+ endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/ß-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/ß-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/ß-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation.

Aspirin relieves the calcification of aortic smooth muscle cells by enhancing the heat shock response.

CONTEXT: Vascular calcification is a major complication of chronic renal failure, which has been identified as an active process partly driven by osteogenic transition of vascular smooth muscle cells (VSMCs). Aspirin could prevent cardiomyocyte damage by inducing heat shock response. OBJECTIVE: This study investigates the effect of aspirin on alleviating VSMC calcification. MATERIALS AND METHODS: An in vitro VSMC calcification model was established by 10-day calcification induction in osteogenic medium. VSMCs were grouped as following: control group (normal medium), calcified group (osteogenic medium) and treated group (osteogenic medium with 1 or 4 mmol/L aspirin). VSMC calcification was evaluated by calcified nodules formation, intracellular calcium concentration and osteoblastic marker (OPN and Runx2) expression. RESULTS: After 10-day culture, the intracellular calcium concentration in calcified group was significantly higher than that in control group (1.16 ± 0.04 vs. 0.14 ± 0.01 µg/mg, p < 0.01), but significantly reduced in 1 mmol/L aspirin treated group (0.74 ± 0.05 µg/mg, p < 0.01), and 4 mmol/L aspirin treated group (0.93 ± 0.03 µg/mg, p < 0.01). The elevated expression of OPN and Runx2 induced by osteogenic medium was significantly relieved after 1 or 4 mmol/L aspirin treatment. The expression of HSF1, HSP70 and HSP90 was decreased in calcification-induced VSMCs, but significantly increased after treatment of aspirin. Furthermore, inhibition of HSP70 (or HSP90) by small-molecule inhibitor or small interfering RNA could partially abolish the anti-calcification effect of aspirin, proved by the changes of intracellular calcium concentration and osteoblastic marker expression. DISCUSSION AND CONCLUSIONS: Aspirin could relieve the calcification of VSMCs partially through HSP70- or HSP90-mediated heat shock response. These findings expanded the understanding of aspirin pharmacology, and imply that local induction expression of HSPs might be a potential therapeutic strategy for the prevention and therapy of vascular calcification.

Identification, isolation and characterization of human LGR5-positive colon adenoma cells.

The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, whereas less is known about human intestinal stem cells owing to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC)-associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5. LGR5-positive cells were isolated from four adenoma organoid lines and were subjected to RNA sequencing. We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA sequencing data from adenoma and normal organoids, we found correlations between LGR5 and CRC-specific genes, including dickkopf WNT signaling pathway inhibitor 4 (DKK4) and SPARC-related modular calcium binding 2 (SMOC2). Collectively, this work provides resources, methods and new markers to isolate and study stem cells in human tissue homeostasis and carcinogenesis.

Short-Video Apps as a Health Information Source for Chronic Obstructive Pulmonary Disease: Information Quality Assessment of TikTok Videos.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become one of the most critical public health problems worldwide. Because many COPD patients are using video-based social media to search for health information, there is an urgent need to assess the information quality of COPD videos on social media. Recently, the short-video app TikTok has demonstrated huge potential in disseminating health information and there are currently many COPD videos available on TikTok; however, the information quality of these videos remains unknown. OBJECTIVE: The aim of this study was to investigate the information quality of COPD videos on TikTok. METHODS: In December 2020, we retrieved and screened 300 videos from TikTok and collected a sample of 199 COPD-related videos in Chinese for data extraction. We extracted the basic video information, coded the content, and identified the video sources. Two independent raters assessed the information quality of each video using the DISCERN instrument. RESULTS: COPD videos on TikTok came mainly from two types of sources: individual users (n=168) and organizational users (n=31). The individual users included health professionals, individual science communicators, and general TikTok users, whereas the organizational users consisted of for-profit organizations, nonprofit organizations, and news agencies. For the 199 videos, the mean scores of the DISCERN items ranged from 3.42 to 4.46, with a total mean score of 3.75. Publication reliability (P=.04) and overall quality (P=.02) showed significant differences across the six types of sources, whereas the quality of treatment choices showed only a marginally significant difference (P=.053) across the different sources. CONCLUSIONS: The overall information quality of COPD videos on TikTok is satisfactory, although the quality varies across different sources and according to specific quality dimensions. Patients should be selective and cautious when watching COPD videos on TikTok.

Exposure time determines the protective effect of Trichinella spiralis on experimental colitis.

Several studies demonstrate the protective effect of Trichinella spiralis (T. spiralis) on autoimmune diseases, however the optimal exposure time remains unexplored. This study aimed to determine whether pre-exposure of mice to T. spiralis conferred greater protection than introduction of the parasite in the acute phase of experimental colitis. We compared the effect of T. spiralis on dextran sodium sulfate (DSS)-induced colitis using two exposure paradigms: introduction three weeks prior to, or immediately after the induction period. Inflammation scores, morphological changes and cytokine profiles in serum and colonic tissue were assessed. At a parasite dose of 300 cysts, post exposure had a more pronounced effect on cytokine profiles, improved gross appearance of colon tissue, and reduced inflammatory symptoms. In addition, we demonstrate that regardless of cyst number, pre-exposure to T. spiralis did not confer protective benefits when compared to parasite introduction in the acute phase of DSS-induced colitis. Moreover, our data indicates that the underlying mechanisms of action involve an IL-17/TNF-alpha synergistic reaction, suppression of Th1 and Th2 responses, and an upregulation of the regulatory cytokines IL-10 and TGF-beta 1. Our results demonstrate that moderate exposure to T. spiralis in the acute phase of DSS-induced colitis improves disease associated inflammation and tissue disruption.

Phototropic Aggregation and Light-Guided Long-Distance Collective Transport of Colloidal Particles.

Phoretic swarming and collective transport of colloidal particles in response to environmental stimuli have attracted tremendous interest in a variety of fields. In this work, we investigate the light-actuated motion, aggregation, and light-guided long-distance mass transport of silica microspheres in simple spiropyran solutions under the illumination of UV spot sources. The phototactic motion is confirmed by the dependence of swarming on the illumination intensity and spiropyran concentrations, ON-OFF switching tests, pattern-masked UV sources, etc. The aggregates formed via swarming of silica spheres can chase after a moving UV source, however, relying on a critical speed of the UV source. Only when the UV source speed is below the critical value, the aggregates follow the UV spot at a constant relative speed to the light spot. Analysis on the shape of silica microsphere currents indicates that continuous illumination of the UV spot source and resultant chemical gradients are important for the formation of steady microsphere currents. Light-guided aggregation and long-distance mass transport are interesting for targeted delivery and remote-controlled enrichment of environmental hazards.

NFκB and TNFα as individual key molecules associated with the cisplatin-resistance and radioresistance of lung cancer.

Cisplatin-resistant (A549CisR and H292CisR) and radioresistant (A549R26 and H292R22) sub-line non-small cell lung cancer (NSCLC) cells were developed in our lab by long term treatment of parental cells with cisplatin or radiation. Our data showed no cross-resistance between these two sets of cell lines, indicating that molecular mechanisms of developing each resistance may be different. Using these sub-line cells, we sought to reveal the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, compared with parental cells. In qPCR analyses of screening DNA repair and cell survival-associated molecules, we identified NFκB and TNFα as the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, respectively, compared with parental cells. Western blot analysis of parental vs. resistant cells and the IHC staining of tumor tissues of A549P, A549CisR, and A549R26 cell-derived xenografts in mice confirmed such results. Next, studies using specific inhibitors of NFκB and TNFα and experiments using NFκB and TNFα-knocked down cells showed that inhibition or knockdown of NFκB overcame cisplatin-resistance, while inhibition or knockdown of TNFα increased radiosensitivity of radioresistant lung cancer cells. Therefore, these two molecules may be used as markers of the prognosis/diagnosis of individual resistance development during lung cancer treatment.