Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular Polyamine Signaling.

Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

Application effect of diversified health-promoting models on rehabilitation exercises for cervical spondylotic myelopathy.

BACKGROUND: With improving living standards, the incidence of cervical spondylotic myelopathy (CSM) has become increasingly high. OBJECTIVE: The study aims to explore the effect of diversified health-promoting models on rehabilitation exercises in patients with CSM after an operation. METHOD: This was a randomized controlled trial, wherein 107 patients with CSM treated by neurosurgery were selected as the subjects. Of those, 52 patients in the control group adopted the conventional health-promoting model, while the remaining 55 patients in the intervention group adopted diversified health-promoting models. The effect of rehabilitation exercises in the two groups was evaluated according to the self-efficacy rehabilitation outcome scale, grip strength measurement of the affected limb, and Barthel index. RESULTS: At Day 3 post-operation and before discharge, the self-efficacy management of rehabilitation exercises in the intervention group was better than that of the control group (P< 0.05). The grip strength measurement of the affected limb, Japanese Orthopedic Association score of the cervical vertebra, and Barthel index of the two groups at Day 3 post-operation were lower than before the intervention and were not statistically significant (P> 0.05). However, these three items before discharge were improved when compared with those of before intervention and were statistically significant (P< 0.05). CONCLUSION: Postoperative rehabilitation exercises guided by the diversified health-promoting models for patients with CSM can improve the patients' self-efficacy management ability in rehabilitation exercises, help improve grip strength, and promote the recovery of cervical vertebra function, thereby improving the patients' quality of life.

Analysis of Factors Correlated with Postoperative Kinesiophobia in Patients with Cervical Spondylotic Myelopathy: A Cross-Sectional Survey.

Objective: To investigate the prevalence of postoperative kinesiophobia in patients with cervical spondylotic myelopathy (CSM) and factors influencing the occurrence of kinesiophobia, to provide relevant basis for making clinical decisions for targeted interventions. Methods: We enrolled a total of 85 patients who underwent CSM surgery at two grade-A general public hospitals in Fujian Province between September 2021 and May 2022. We conducted a questionnaire survey using the Tampa Scale for Kinesiophobia (TSK) and the Zung Self-Rating Anxiety Scale (SAS). Patients evaluated pain using a visual analogue scale. We used one-way ANOVA and logistic multiple regression analysis to identify the relevant influencing factors. Results: The TSK score was (41.88±4.46) in 85 postoperative CSM patients, 65 males and 20 females, and there were 31 patients under 40 years old, 54 patients over 40 years old, 58 patients below high school education and 27 patients above high school education, and among them, 81.17% were diagnosed with kinesiophobia. Age was positively correlated with TSK score (r = 0.379, P < 0.05) and therefore a risk factor for kinesiophobia (OR = 1.941, 95% CI = 1.021-3.690). Additionally, the duration of the disease was a protective factor for kinesiophobia (OR = 0.179, 95% CI = 0.053-0.605). Conclusion: Patients with CSM were at high risk of developing kinesiophobia postoperatively. Age and duration of the disease were factors influencing the occurrence of kinesiophobia in this group.

[Corrigendum] Epigallocatechin­3­gallate inhibits nicotine­induced migration and invasion by the suppression of angiogenesis and epithelial­mesenchymal transition in non­small cell lung cancer cells.

Subsequently to the publication of the above paper, the authors have drawn to the attention of the Editorial Office that a pair of the data panels showing the results of wound­healing assay experiments (in Fig. 1A) and Transwell invasion assays (in Fig. 1B) on p. 2975 were inadvertently featured incorrectly in this figure. Specifically, in Fig. 1A, the 'nicotine + 25 µM EGCG / 0 h' data panel was erroneously copied across to represent the 'nicotine + 0 µM EGCG / 0 h' image, whereas in Fig. 1B, the representative invasion image for the 'nicotine + 10  µM  EGCG' experiment was also incorrectly placed. The authors were able to re­examine their original data files, and realize how the errors were made during the assembly of this figure. The revised version of Fig. 1, showing the correct data for the 'nicotine + 0 µM EGCG / 0 h' in Fig. 1A and the 'nicotine + 10  µM  EGCG' experiment in Fig. 1B, is shown on the next page. Note that the errors made in assembling this figure did not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and all the authors agree with its publication. They also apologize to the readership for any inconvenience caused. [Oncology Reports 33: 2972­2980, 2015; DOI: 10.3892/or.2015.3889].

The upregulation of peripheral blood polyamine metabolites spermidine and spermine in children with hand, foot, mouth disease is related to enterovirus 71 capsid protein VP1, but not VP4.

Background: Hand, foot, and mouth disease (HFMD) is a common viral childhood illness caused most commonly by enterovirus 71 (EV71) and coxsackievirus A16. The pathogenesis of EV71 has been extensively studied, and the regulation of the host immune response is suspected to aggravate the serious complications induced by EV71. Our previous research showed that EV71 infection significantly increased the release of circulating interleukin (IL)-6, IL-10, IL-13, and IL-27. Notably, these cytokines are related to the EV71 infection risk and clinical stage. Polyamines are compounds that are ubiquitous in mammalian cells and play a key role in various cellular processes. Several studies have shown that targeting polyamine metabolic pathways can reduce infections caused by viruses. However, the significance of polyamine metabolism in EV71 infection remains largely unknown. Methods: Serum samples from 82 children with HFMD and 70 healthy volunteers (HVs) were collected to determine the polyamine metabolites spermidine (SPD) and spermine (SPM), and IL-6 levels. In addition, peripheral blood mononuclear cells (PBMCs) were treated with EV71 viral protein 1 (VP1) and EV71 VP4, and the cells and supernatant were then collected to analyze the expression of polyamine metabolism-related enzymes by western blot. The data were analyzed using GraphPad Prism 7.0 software (USA). Results: The serum polyamine metabolites SPD and SPM were elevated in the HFMD patients, especially in the EV71-infected children. Further, a positive correlation was found between serum SPD and IL-6 levels in the EV71-infected children. We also found that the upregulation of peripheral blood polyamine metabolites in the EV71-infected HFMD children was related to EV71 capsid protein VP1, but not VP4. VP1 may promote the expression of polyamine metabolism-related enzymes and promote the production of polyamine metabolites, thereby upregulating the SPD/nuclear factor kappa B/IL-6 signaling pathway. However, VP4 has the opposite effect in this process. Conclusions: Our results suggest that EV71 capsid protein may regulate the polyamine metabolic pathways of infected cells in a variety of ways. This study provides insights into the mechanism of EV71 infection and polyamine metabolism and has good reference value for the development of EV71 vaccine.

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment.

The study of metabolism provides important information for understanding the biological basis of cancer cells and the defects of cancer treatment. Disorders of polyamine metabolism is a common metabolic change in cancer. With the deepening of understanding of polyamine metabolism, including molecular functions and changes in cancer, polyamine metabolism as a new anti-cancer strategy has become the focus of attention. There are many kinds of polyamine biosynthesis inhibitors and transport inhibitors, but not many drugs have been put into clinical application. Recent evidence shows that polyamine metabolism plays essential roles in remodeling the tumor immune microenvironment (TIME), particularly treatment of DFMO, an inhibitor of ODC, alters the immune cell population in the tumor microenvironment. Tumor immunosuppression is a major problem in cancer treatment. More and more studies have shown that the immunosuppressive effect of polyamines can help cancer cells to evade immune surveillance and promote tumor development and progression. Therefore, targeting polyamine metabolic pathways is expected to become a new avenue for immunotherapy for cancer.

Mesenchymal stem/stromal cells in the pathogenesis and regenerative therapy of inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) represent a group of chronic inflammatory disorders of the gastrointestinal (GI) tract including ulcerative colitis (UC), Crohn's disease (CD), and unclassified IBDs. The pathogenesis of IBDs is related to genetic susceptibility, environmental factors, and dysbiosis that can lead to the dysfunction of immune responses and dysregulated homeostasis of local mucosal tissues characterized by severe inflammatory responses and tissue damage in GI tract. To date, extensive studies have indicated that IBDs cannot be completely cured and easy to relapse, thus prompting researchers to find novel and more effective therapeutics for this disease. Due to their potent multipotent differentiation and immunomodulatory capabilities, mesenchymal stem/stromal cells (MSCs) not only play an important role in regulating immune and tissue homeostasis but also display potent therapeutic effects on various inflammatory diseases, including IBDs, in both preclinical and clinical studies. In this review, we present a comprehensive overview on the pathological mechanisms, the currently available therapeutics, particularly, the potential application of MSCs-based regenerative therapy for IBDs.

Gingiva-Derived Mesenchymal Stem Cells Attenuate Imiquimod- (IMQ-) Induced Murine Psoriasis-Like Skin Inflammation.

Human gingiva-derived mesenchymal stem cells (GMSCs) are isolated from the gingival propria with promising regenerative, immunomodulatory, and anti-inflammatory properties. Recently, several studies, including ours, have found that GMSCs have the therapeutic potentials of nerve regeneration and skin disorders in various types such as the cell itself, cell-free conditioned medium, or extracellular vesicles (EVs). However, the mechanobiological behavior of GMSCs is closely related to the culture conditions. Therefore, the purpose of this study was to evaluate the function of human GMSCs on imiquimod- (IMQ-) induced murine psoriasis-like skin inflammation in two-dimensional (2D) and three-dimensional (3D) culture conditions. Here, we isolated and characterized GMSCs in 2D and 3D culture conditions and found that GMSCs in 2D and 3D infusion can significantly ameliorate the IMQ-induced murine psoriasis-like skin inflammation, reduce the levels of Th1- and Th17-related cytokines IFN-γ, TNF-α, IL-6, IL-17A, IL-17F, IL-21, and IL-22, and upregulate the percentage of spleen CD25+CD3+ T cells while downregulate the percentage of spleen IL-17+CD3+ T cells. In summary, our novel findings reveal that GMSCs in 2D and 3D infusion may possess therapeutic effects in the treatment of psoriasis.

Investigation and Analysis of Influencing Factors of Moderate to Severe Pain After Uterine Artery Embolization in Patients with Cesarean Scar Pregnancy.

OBJECTIVE: To investigate the occurrence and influencing factors of moderate to severe pain in patients with cesarean scar pregnancy (CSP) after uterine artery embolization (UAE). METHODS: Ninety-eight patients with CSP who underwent UAE in gynecology department of the Fujian Medical University Union Hospital from January 2017 to December 2020 were enrolled, and the specialty data in patients were collected for pain assessment with the adoption of the numerical rating scale (NRS). RESULTS: Moderate to severe pain occurred in 36 patients after surgery, and the interquartile of time to the first onset of postoperative pain in patients was 3.04 (1.75, 7.40) hours. The number of pregnancies, number of miscarriages, human chorionic gonadotropin (HCG) before curettage, duration of medication before UAE, and hemorrhage after UAE were not significantly correlated with the occurrence of moderate to severe pain after UAE (P > 0.05). The volume of gestational sac and days of gestation were responsible for the occurrence of moderate to severe pain after UAE (P < 0.05), with the former being the main influencing factor, and these explained 8.3% of the total variance. CONCLUSION: Moderate to severe pain occurred commonly in patients with CSP undergoing UAE. In clinical care of patients with CSP who are going to undergo UAE, data concerning the volume of gestational sac and days of gestation should be considered for anticipatory pain assessment, and interventions should be implemented as early as possible to reduce the pain and improve the experience of care.

Perceived-stigma level of COVID-19 patients in China in the early stage of the epidemic: A cross-sectional research.

OBJECTIVE: To investigate the perceived-stigma level of COVID-19 patients in the early stage of the epidemic and analysed related factors and correlations that affected the stigma levels. METHODS: The COVID-19 patients were selected using the convenience sampling method. Perceived-stigma level was evaluated using the Social Impact Scale (SIS). Frequency was used to describe the general information and disease investigation status of COVID-19 patients; mean and standard deviation were used for describing stigma levels, Wilcoxon signed-ranks test (nonparametric test) was applied for pairwise comparison. Kruskal-Wallis non-parametric test for grade data, and Dwass-Steel-Critchlow-Fligner test for multiple comparative analysis. Multiple linear regression analysis was performed, and statistically significant indicators in single-factor analysis were included to investigate the independent factors of stigma. The p<0.05 was considered statistically significant. RESULTS: SIS score of the 122 COVID-19 patients averaged 57.37±9.99 points. There were statistically significant differences in perceived-stigma levels among patients of different ages (p = 0.008), occupation (p <0.001), marital status (p = 0.009), and disease severity (p = 0.020). Multivariate logistic regression analysis revealed that age was the main influencing factor of stigma (p<0.05). CONCLUSIONS: The overall perceived-stigma level of COVID-19 patients in the early stage of the epidemic was moderate. Younger, unmarried, and severely ill patients had a higher level of perceived-stigma, with age being the main factor. More attention should be given to the young COVID-19 patients.

Lactobacillus paracasei R3 protects against dextran sulfate sodium (DSS)-induced colitis in mice via regulating Th17/Treg cell balance.

Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine dextran sulfate sodium (DSS)-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.

Beta-1 syntrophin (SNTB1) regulates colorectal cancer progression and stemness via regulation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: Beta-1 syntrophin (SNTB1) is an intracellular scaffold protein that provides a platform for the formation of signal transduction complexes, thereby modulating and coordinating various intracellular signaling events and crucial cellular processes. However, the physiological role of SNTB1 is poorly understood. This study aims to explore the role of SNTB1 in colorectal cancer (CRC) tumorigenesis and progression, with particular focus on SNTB1's expression pattern, clinical relevance, and possible molecular mechanism in CRC development. METHODS: SNTB1 expression was analyzed in both clinical tissues and The Cancer Genome Atlas (TCGA) database. Real-time polymerase chain reaction (PCR), Western blot, and immunohistochemical assays were used to detect the relative mRNA and protein levels of SNTB1. Statistical analysis was performed to examine the correlation between SNTB1 expression and the clinicopathological characteristics of patients with CRC. Bioinformatics gene set enrichment analysis (GSEA), Western blot, luciferase assay, and agonist recovery assays were conducted to evaluate the relevance of SNTB1 and the ß-catenin signaling pathway in CRC. A flow cytometry-based Hoechst 33342 efflux assay was applied to assess the proportion of the side population (SP) within total CRC cells. RESULTS: Elevated levels of SNTB1 were identified in CRC tissues and cell lines. The elevation of SNTB1 was positively correlated with the degree of malignancy and poor prognosis in CRC. We further revealed that, by modulating the ß-catenin signaling pathway, silencing SNTB1 expression suppressed tumor growth and cancer stemness in vitro, as well as tumorigenesis in vivo. CONCLUSIONS: These findings suggest that SNTB1 plays a crucial role in colorectal tumorigenesis and progression by modulating ß-catenin signaling and the stemness maintenance of cancer cells.

Hope Levels and Resilience in Patients with Severe Novel Coronavirus Pneumonia: The Current Situation and a Correlation Analysis.

OBJECTIVE: The study aims to analyze the correlation between hope levels and resilience in patients with severe novel coronavirus pneumonia (COVID-19). METHODS: Fifty-six patients with severe COVID-19 were investigated, with the use of a general information questionnaire, the Herth Hope Index, and the Connor-Davidson resilience scale. RESULTS: There was a significant difference in patients' hope levels with respect to marital status and educational background (P < 0.05), and there was a significant difference in resilience scores depending on gender and family economic situation (P < 0.05). In the present study, the hope levels and resilience in the patients were moderate, with an average score of (34.93 ± 5.45) and (69.36 ± 15.52), respectively. There was a significant positive correlation between the hope level and the resilience score in these patients (P < 0.05). CONCLUSION: In patients with severe COVID-19, the higher the hope level, the higher the resilience score.

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis.

The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.

ALKAL1 gene silencing prevents colorectal cancer progression via suppressing Sonic Hedgehog (SHH) signaling pathway.

Anaplastic lymphoma kinase (ALK) has been described in a range of human cancers and is involved in cancer initiation and progression via activating multiple signaling pathways, such as the PI3K-AKT, CRKL-C3G, MEKK2/3-MEK5-ERK5, JAK-STAT and MAPK signal pathways. Recently ALK and LTK ligand 1 (ALKAL1) also named "augmentor-ß" or "FAM150A" is identified as a potent activating ligands for human ALK that bind to the extracellular domain of ALK. However, due to its poor stability, the mechanisms of ALKAL1 underlying the tumor progression in the human cancers including colorectal cancer have not been well documented. Herein, ALKAL1 expression was evaluated by RNA sequencing datasets from The Cancer Genome Atlas (TCGA) of 625 cases colorectal cancer, immunohistochemical analysis of 377 cases colorectal cancer tissues, and Western blotting even Real-time PCR of 10 pairs of colorectal cancer tissues and adjacent normal tissues, as well as 8 colorectal cancer cell lines. Statistical analysis was performed to explore the correlation between ALKAL1 expression and clinicopathological features in colorectal cancer. Univariate and multivariate Cox regression analysis were performed to examine the association between ALKAL1 expression and overall survival. In vitro and in vivo assays were performed to assess the biological roles of ALKAL1 in colorectal cancer. Gene set enrichment analysis (GSEA), Western blotting and luciferase assays were used to identify the underlying signal pathway involved in the tumor progression role of ALKAL1. As a result, we showed that ALKAL1 was upregulated in colorectal cancer tissues and cell lines. Upregulation of ALKAL1 correlated with tumor malignancy and poor prognosis in colorectal cancer. ALKAL1 silencing inhibited tumorigenesis, metastasis and invasion of colorectal cancer cells, and inhibited SHH signaling pathway, which is essential for ALKAL1 induced migration. Our findings reveal a new mechanism by which ALKAL1 participates in colorectal cancer migration and invasion via activating the SHH signaling pathway.

Aberrant expression of miR-16, B12 and CD272 in peripheral blood mononuclear cells from patients with active tuberculosis.

Tuberculosis (TB) immunity is affected by complex immune regulation processes, which involve various immune cells, immune molecules, and cytokines. Here, we evaluated the expression of B12, CD272 and miR-16 in peripheral blood mononuclear cells (PBMC) of patients with active pulmonary tuberculosis. The results showed that monocytes expressing CD272 or B12 were down-regulated in patients with tuberculosis. The expression of B12 and CD272 in T cells and monocytes is related to tuberculosis. In TB patients, the up-regulation of miR-16 was negatively correlated with B12 mRNA expression, miR-16 was mainly expressed in CD14+ monocytes, and CD272 mRNA was mainly expressed in CD19+ B cells. It is worth noting that the overexpression of miR-16 inhibits the expression of CD272 and B12 in monocytes of TB patients. After BCG stimulation, miR-16 expression of CD14+ monocytes was up-regulated and B12 mRNA and CD272 mRNA expressions were down-regulated in TB patients. Finally, we found that miR-16 may participate in the TB immunization process through targeted regulation of B12 expression. These studies indicate that the expression of B12, CD272 and miR-16 in PBMC may be related to tuberculosis.

Lesson learned from China regarding use of personal protective equipment.

BACKGROUND: In Wuhan, China, in December 2019, the novel coronavirus was detected. The virus causing COVID-19 was related to a coronavirus named severe acute respiratory syndrome coronavirus (SARS-CoV). The virus caused an epidemic in China and was quickly contained in 2003. Although coming from the same family of viruses and sharing certain transmissibility factors, the local health institutions in China had no experience with this new virus, subsequently named SARS-CoV-2. METHODS: Based on their prior experience with the 2003 SARS epidemic, health authorities in China recognized the need for personal protective equipment (PPE). Existing PPE and protocols were limited and reflected early experience with SARS; however, as additional PPE supplies became available, designated COVID-19 hospitals in Hubei Province adopted the World Health Organization guidelines for Ebola to create a protocol specific for treating patients with COVID-19. RESULTS: This article describes the PPE and protocol for its safe and effective deployment and the implementation of designated hospital units for COVID-19 patients. To date, only 2 nurses working in China who contracted SARS-CoV-2 have died from COVID-19 in the early period of the epidemic (February 11 and 14, 2020). CONCLUSIONS: The lessons learned by health care workers in China are shared in the hope of preventing future occupational exposure.

Ectodysplasin A receptor (EDAR) promotes colorectal cancer cell proliferation via regulation of the Wnt/ß-catenin signaling pathway.

Colorectal cancer is the second leading cause of cancer mortality worldwide with poor prognosis and high recurrence. Aberrant Wnt/ß-catenin signaling promotes oncogenesis by transcriptional activation of c-Myc and its downstream signals. EDAR is characterized as an important effector of canonical Wnt signaling in developing skin appendages, but the interplay between EDAR and Wnt signaling in tumorigenesis and progression remains to be elucidated. In this study, we revealed that EDAR expression is prevalently elevated in colorectal cancer tissues compared with normal tissues. Further analysis suggests there is a strict correlation between EDAR expression and colorectal cancer progression. EDAR silencing by shRNA in colorectal cancer cells showed proliferative suppression via retarding cell cycle at G1 phase. Xenograft mice transplanted with shEDAR-transduced tumor cells significantly alleviated tumor burden in comparison with control mice. Furthermore, downregulation of EDAR was accompanied by reduction of ß-catenin, c-Myc and other G1 cell cycle regulators, while ß-catenin agonist restored the expression of these proteins and overrode the proliferative block induced by EDAR knockdown. These findings indicate that EDAR functions as a component of Wnt/ß-catenin signaling pathway, and is a potential modulator in colorectal carcinogenesis.

Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression.

Previous studies have implicated the important role of mesenchymal stem/stromal cells (MSCs) within tumor microenvironment (TME) in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), but the potential mechanisms are still unclear. Herein, we showed that an elevated IL-6 level was positively correlated with elevated expression of CD73 in TME of NPC. NPC specimens with an IL-6highCD73high phenotype showed higher expression levels of gp80, gp130, p-STAT3, MMP-9 and α-SMA, and clinically, a poorer prognosis than those with an IL-6lowCD73low phenotype. We found that stimulation with conditioned media derived from IL-6 gene knocked out MSC (MSCIL6KO-CM) down-regulated the expression of CD73, IL-6, gp80, p-STAT3, and proliferative cell nuclear antigen (PCNA) in CNE-2 NPC cells. Meanwhile, NPC cells co-cultured with MSCIL6KO-CM were more sensitive to cisplatin than those co-cultured with MSC-CM. Additionally, MSC-derived IL-6 transcriptionally upregulated CD73 expression via activating STAT3 signaling pathway in NPC cells. In summary, our findings suggest that MSCs promote NPC progression and chemoresistance by upregulation of CD73 expression via activating STAT3 signaling pathway.

Triple-high expression of phosphatase and tensin homolog (PTEN), estrogen receptor (ER) and progesterone receptor (PR) may predict favorable prognosis for patients with Type I endometrial carcinoma.

Endometrial carcinoma (EC) is the most common malignant tumors in female derived from the endometrial epithelium. Several previous studies have described estrogen receptors (ER), progesterone Receptor (PR) and phosphatase and tensin homolog (PTEN) are associated with clinicopathological factors and prognosis in EC patients. However, during EC patients follow-up, we found that some EC patients with down-regulation of PTEN, but up-regulation of ER or PR , and some EC patients with down-regulation of ER or PR, but up-regulation of PTEN also had a poor prognosis. Therefore, to reveal the prognosis of EC patients with different phenotypes based on PTEN, ER and PR expression, 120 cases formalin-fixed paraffin-embedded EC tissues and 543 cases uterine corpus endometrial carcinoma (UCEC) patients from the cancer genome atlas (TCGA) UCEC datasets were analyzed. Results showed that EC tissues can be classified to PTENLERLPRL, PTENHERLPRL, PTENHERHPRH, PTENLERHPRH, PTENHERHPRL, PTENHERLPRH, and PTENLERHPRL phenotypes basing on IHC analysis. Additionally, EC patients with PTENLERLPRL showed high malignancy, while patients with PTENHERHPRH showed low malignancy. Therefore, combined detection of PTEN, ER, PR may help identify a small subset of EC with more aggressive behavior and may aid in risk stratification.