Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway.

Rosacea is a chronic facial inflammatory skin disease that occurs with dysfunction of the immune system. Colchicine was reported to have anti-inflammatory properties. However, the impact of colchicine on rosacea remains unclear. In the present study, the phenotype of rosacea lesions was evaluated by the redness score, inflammatory biomarkers were analyzed by reverse transcription PCR (RT‒PCR), and the infiltration of inflammatory cells was assessed by IHC analysis and immunofluorescence in a rosacea-like mouse model. In vitro, RT‒PCR was used to identify the inflammatory factors that Toll-like receptor 2 (TLR2) agonist caused neutrophils to produce, and immunofluorescence and coimmunoprecipitation were used to identify putative signalling pathways. We found that skin erythema and histopathological alterations, as well as elevated proinflammatory factors (IL-1ß, IL-6, TNFα, CXCL2) and CAMP, were significantly ameliorated by colchicine treatment in LL37-induced rosacea-like mice. In addition, colchicine reduced the colocalization of TLR2 and neutrophils and the formation of neutrophil extracellular trap networks (NET) in mouse lesions. In neutrophils, colchicine markedly reduced TLR2 agonist-induced inflammatory biomarker expression, NET formation, and ROS production. Moreover, we found that LL37 could bind to TLR2 upon activation of TLR2 in neutrophils. Importantly, colchicine could repress the combination of TLR2 and LL37 in vivo. Finally, bioinformatics methods further validated the key molecules of neutrophil-related inflammation in rosacea, which is consistent with our experimental findings. Collectively, colchicine ameliorated rosacea-like dermatitis by regulating the neutrophil immune response activated by the TLR2 pathway, indicating that it could be an effective therapeutic option for patients with rosacea.

A nomogram for predicting survival in patients with skin non-keratinizing large cell squamous cell carcinoma: A study based on the Surveillance, Epidemiology, and End Results database.

Introduction: This study aimed to develop and validate a nomogram for predicting cancer-specific survival (CSS) in patients with non-keratinized large cell squamous cell carcinoma (NKLCSCC) at 3, 5, and 8 years after diagnosis. Methods: Data on SCC patients were collected from the Surveillance, Epidemiology, and End Results database. Training (70%) and validation (30%) cohorts were generated using random selection of patients. Independent prognostic factors were selected using the backward stepwise Cox regression model. To predict the CSS rates in patients with NKLCSCC at 3, 5, and 8 years after diagnosis, all of the factors were incorporated into the nomogram. Indicators such as the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (AUC), net reclassification index (NRI), integrated discrimination improvement (IDI), calibration curve, and decision-curve analysis (DCA) were then used to validate the performance of the nomogram. Results: This study included 9,811 patients with NKLCSCC. Twelve prognostic factors were identified by Cox regression analysis in the training cohort, which were age, number of regional nodes examined, number of positive regional nodes, sex, race, marital status, American Joint Committee on Cancer (AJCC) stage, surgery status, chemotherapy status, radiotherapy status, summary stage, and income. The constructed nomogram was validated both internally and externally. The nomogram had good discrimination ability, as indicated by the comparatively high C-indices and AUC values. The nomogram was properly calibrated, as indicated by the calibration curves. Our nomogram was superior to the AJCC model, as illustrated by its superior NRI and IDI values. DCA curves indicated the clinical usability of the nomogram. Conclusion: The first nomogram for prognosis predictions of patients with NKLCSCC has been developed and verified. Its performance and usability demonstrated that the nomogram could be utilized in clinical settings. However, additional external verification is still required.

RJT-101, a novel camptothecin derivative, is highly effective in the treatment of melanoma through DNA damage by targeting topoisomerase 1.

Melanoma is one of the most aggressive malignancies. Drug resistance and toxicity limits the clinical efficacy of melanoma chemotherapeutic drugs such as dacarbazine. Therefore, the development of chemotherapeutic agents for melanoma treatment is urgently needed. RJT-101 significantly inhibits the proliferation of melanoma cells, however has low cytotoxicity to non-malignant cells. RJT-101 induces apoptosis, DNA damage, and G2/M phase arrest, as a consequent, attenuates tumor growth, lung metastasis in vivo as well as prolongs survival of tumor bearing mice. RJT-101 could block topoisomerase I (Top1) activity as well as induce its degradation through proteasome system. Interestingly, Top1 is over-expressed in melanoma cells, compared to non-malignant cells. Knock down of Top1 suppresses melanoma cells growth and induces apoptosis and DNA damage in melanoma cells. RJT-101 effectively inhibits melanoma cells (including vemurafenib-resistant melanoma cells) proliferation in vitro and in vivo through the induction of DNA damage and apoptosis by inhibiting of Top1, indicating RJT-101 warrants further clinical evaluation.

Titration of cell-associated varicella-zoster virus with the MV9G reporter cell line for antiviral studies.

Titration of the cell-associated virus (CAV) of varicella-zoster virus (VZV) is essential for antiviral studies. A VZV reporter cell line, MV9G, generated in our previous study expresses firefly luciferase upon CAV infection in a dose-dependent manner, suggesting that use of the cell line for titration is feasible. In this study, MeWo cells infected with VZV vaccine Oka (vOka) strain or with clinical isolates obtained from patients with varicella or zoster were used as CAV. A co-culture of MV9G cells with the virus-infected MeWo cells were set up and optimized for titration of CAV. Luciferase activities of MV9G cells measured as relative light units (RLUs) of chemiluminescence correlated well (r > 0.9, p < 0.05) both with quantities of viral DNAs measured by TaqMan PCR and with numbers of viral foci detected by immunostaining with a monoclonal antibody against VZV IE62. In addition, the usefulness of MV9G for antiviral studies was exemplified by treatment of the VZV-infected cells with various concentrations of acyclovir. Thus, the reporter cell-based titration of CAV by measuring the induced RLUs may be a reliable way to estimate viral foci and viral DNAs.

Targeting CD147 is a Novel Strategy for Antitumor Therapy.

CD147 is a membrane protein belonging to immunoglobulin superfamily and expressed in the cell membrane, which is also named with an extracellular matrix metalloproteinase inducer (EMMPRIN) because this molecule induces adjacent fibroblasts or tumor cells to produce MMPs, facilitating tumor cells migration and invasion. Accumulating evidences have shown that CD147 is over-expressed in various tumors, including melanoma, liver cancer, and lung cancer, and orchestrates tumor cell proliferation, apoptosis, invasion and metastasis, multidrug resistance and glycolysis through critical molecules such as MMPs, MCTs, Caveolin-1, and VEGF. In this review, we focus on understanding the characteristics of CD147 in various biological functions, including physiological and pathological processes. Recent novel studies have shown that CD147 is not only a potential diagnostic marker but also a therapeutic target for chemotherapy or the diagnosis of cancer.