2-Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway.

BACKGROUND: The MAPK/Erk signaling pathway is a classic pathway in cell proliferation. Our former study showed that keloid tissue revealed a higher proliferation level than physiological scars and normal skin. As a natural metabolite of estradiol, 2-methoxyestradiol (2ME2) showed an inhibition proliferation effect on tumor cells. AIM: In this study, the treatment effect of 2ME2 and its potential mechanisms are explored. METHODS: Six keloid patients and six non-keloid patients were randomly selected from the Department of Plastic Surgery at our hospital during June 2021 to December 2021. Six groups were established: normal skin fibroblasts (N); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (K + 2ME2); keloid fibroblasts treated with dimethyl sulfoxide (DMSO) (K + DMSO); keloid fibroblasts treated with doramapimod (K + IN); keloid fibroblasts treated with doramapimod (p38 inhibitor) and 2ME2 (K + IN+2ME2). The fibroblast activity and key factor expression of the MAPK/Erk signaling pathway were measured. RESULTS: In the results, 2ME2 significantly inhibited keloid fibroblast activity and key factor expression (except STAT1). CONCLUSION: The proliferation levels were reduced by both the p38 inhibitor and 2ME2, indicating 2ME2 may achieve an antiproliferation effect by targeting p38 in keloid fibroblasts.

Role of HIF-1α in pathogenic mechanisms of keloids.

BACKGROUDS AND OBJECTIVE: Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids. METHODS: We reviewed and summarized the relevant published studies. RESULTS: Hypoxia results in the accumulation of hypoxia-inducible factor 1α (HIF-1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial-mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance. CONCLUSION: It is, therefore, essential to understand the role of HIF-1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.

Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation.

Immune checkpoint blockade is considered a breakthrough in cancer treatment. However, with the low response rates and therapeutic resistance of patients with hepatocellular carcinoma (HCC), the challenges facing the application of this treatment are tremendous. Liver fibrosis is a key driver of tumor immune escape, the underlying mechanism has never been clarified. This study sought to explore the role of liver fibrosis in regulating tumor-infiltrating lymphocytes (TILs) and inducing tumor immunosuppression. Ninety-nine fixed HCC tissue samples were used to analyze the association between liver fibrosis and immune escape using immunohistochemistry. In HCC patients, low FIB-4 values and high CD8+ T cell infiltration were correlated with prolonged survival. Elevated expression of immune checkpoints and attenuated antitumor immunity were observed in CCl4-induced mice liver fibrosis models and human fibrotic livers compared to control group. GOLM1 levels were increased in livers of patients with fibrosis and mice in response to CCl4-induced liver fibrosis. CD8+ T cell infiltrations were significantly decreased and PD-L1 expression was significantly increased in tumor tissues from hepatocyte-specific GOLM1 transgenic mice (Alb/GOLM1 mice) inducing chemical carcinogenesis compared to their corresponding control WT mice. GOLM1 induced PD-L1 expression via EGFR pathway activation. EGFR inhibitors, especially together with anti-PD-L1 therapy, improved the efficacy of immunotherapy in HCC. These findings illustrate the importance of liver fibrosis-induced immunosuppression as a tumor-promoting mechanism. GOLM1, which is highly upregulated in the fibrotic liver, regulates tumor microenvironmental immune escape via the EGFR/PD-L1 signaling pathway. EGFR blockade may bolster the efficacy of immune checkpoint inhibitors for HCC treatment.

Chinese medical students' interest in COVID-19 pandemic.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) happened in early December and it has affected China in more ways than one. The societal response to the pandemic restricted medical students to their homes. Although students cannot learn about COVID-19 through clinical practice, they can still pay attention to news of COVID-19 through various channels. Although, as suggested by previous studies, some medical students have already volunteered to serve during the COVID-19 pandemic, the overall willingness of Chinese medical students to volunteer for such has not been systematically examined. AIM: To study Chinese medical students' interest in the relevant knowledge on COVID-19 and what roles they want to play in the pandemic. METHODS: Medical students at Peking Union Medical College were surveyed via a web-based questionnaire to obtain data on the extent of interest in the relevant knowledge on COVID-19, attitude towards volunteerism in the pandemic, and career preference. Logistic regression modeling was used to investigate possible factors that could encourage volunteerism among this group in a pandemic. RESULTS: A total of 552 medical students responded. Most medical students showed a huge interest in COVID-19. The extent of students' interest in COVID-19 varied among different student-classes (P < 0.05). Senior students had higher scores than the other two classes. The number of people who were 'glad to volunteer' in COVID-19 represented 85.6% of the respondents. What these students expressed willingness to undertake involved direct, indirect, and administrative job activities. Logistic regression analysis identified two factors that negatively influenced volunteering in the pandemic: Student-class and hazards of the voluntary job. Factors that positively influenced volunteering were time to watch COVID-19 news, predictable impact on China, and moral responsibility. CONCLUSION: More innovative methods can be explored to increase Chinese medical students' interest in reading about the relevant knowledge on COVID-19 and doing voluntary jobs during the pandemic.

[Overexpression of Axin inhibits lymphoma cell invasion and metastasis in vitro by down-regulating ß-catenin and MMP7/MMP9].

OBJECTIVE: To investigate that the role of Axin in regulating the invasion and migration ability of lymphoma cells and explore the molecular mechanisms. METHODS: The expressions of Axin, ß-catenin, MMP7, and MMP9 were detected in different lymphoma cell lines by RT-PCR and Western blotting. A lymphoma cell line with low Axin expressions was transiently transfected with pCMV5-HA-Axin and pcDNA5-His-ß-catenin plasmid, and the expressions of ß-catenin, MMP7, and MMP9 mRNA and protein were observed. A lymphoma cell model stably overexpressing Axin was transfected with AXIN-shRNA and ß-catenin-shRNA, and the changes in ß-catenin, MMP7, and MMP9 cexpressions were observed. The changes in the invasion and migration abilities of this cell model were assessed following Axin knockdown. RESULTS: In the lymphoma cell lines tested, the Axin expression showed a negative correlation with ß-catenin, MMP7, and MMP9 expressions. In Raji cells with a low Axin expression, overexpression of Axin resulted in decreased expressions of ß-catenin, MMP7, and MMP9 at the protein levels but not the mRNA levels, and overexpression of ß-catenin obviously increased MMP7 and MMP9 mRNA and protein expressions. In the cells with stable Axin overexpression, Axin knockdown caused increased expressions of ß-catenin, MMP7, and MMP9 at the protein levels but not the mRNA levels, while ß-catenin knockdown caused lowered expressions of MMP7 and MMP9 and suppressed cell invasion and migration. CONCLUSION: In lymphoma cells, Axin overexpression can decrease the expression of ß-catenin, which in turn decreases the expressions of MMP7 and MMP9 to inhibit the cell invasion and migration.

[Incomplete palate cleft patient with mirror-image dextrocardia and situs inversus viscerums: report of one case].

Cleft palate is one of the most common congenital defects, occurring alone or in combination with other malformations. Cleft palate with mirror-image dextrocardia and situs inversus viscerums is rare. This paper presented a case of incomplete cleft palate patient with mirror-image dextrocardia and situs inversus viscerums. The patient had a family history of cleft palate and had no family history of congenital heart disease. He was found to have congenital heart disease during preoperative assessment. Without intracardiac malformation, the patient was routinely operated under general anesthesia. The patient had an uneventful postoperative course and was discharged 8 days after operation. Further investigation is needed whether multiple defects in this patient are independent diseases or a part of possible recessive syndrome.