Combination of 308-nm excimer laser and piperine promotes melanocyte proliferation, migration, and melanin content production via the miR-328/SFRP1 axis.

OBJECTIVE: Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. METHODS: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. RESULTS: The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/ß-catenin signaling pathway. CONCLUSION: The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/ß-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.

Integrated Fault-Tolerant Control Design With Sampled-Output Measurements for Interval Type-2 Takagi-Sugeno Fuzzy Systems.

This article is concerned with the integrated design of fault estimation (FE) and fault-tolerant control (FTC) for uncertain nonlinear systems suffering from actuator faults and external disturbance. The uncertain nonlinear systems are characterized as the interval type-2 (IT2) Takagi-Sugeno (T-S) fuzzy model, and IT2 membership functions are employed to effectively handle uncertainties. A fuzzy observer, utilizing only sampled-output measurements, is applied to simultaneously estimate actuator faults and system states. Based on the estimation, the fault-tolerant controller is designed to ensure the system stability under a predefined H∞ performance. The sampling behavior complicates the system dynamics and makes the integrated FTC design more challenging. To confront this issue, the discontinuous Lyapunov functional technique is exploited to enhance stability results by considering the sampling characteristic, upon which FE and FTC units are co-designed in the linear matrix inequality (LMI) framework. To further relax stability criteria, the analysis process incorporates the bound information of membership functions through the membership-function-dependent (MFD) method. Additionally, the relationship of mismatched premise variables resulting from the sampling scheme is also taken into account. Moreover, considering the imperfect premise matching (IPM) framework, the proposed fault-tolerant controller provides greater flexibility in selecting the shapes of membership functions and number of fuzzy rules that can vary from the counterpart of the fuzzy system. Finally, the efficacy of the proposed FTC technique is validated through a detailed numerical example.

M6A methylation of FKFB3 reduced pyroptosis of gastric cancer by NLRP3.

Gastric cancer is a kind of malignant tumor that seriously endangers human life and health. Its incidence rate and mortality rate are among the highest in the global malignant tumors. Therefore, this study explored the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the progression of gastric cancer and its underlying mechanism. Patients with gastric cancer were collected, and human GC cell lines (stomach gastric carcinoma 7901, stomach gastric carcinoma 823 , human gastric carcinoma cell line 803 and adenocarcinoma gastric stomach) were used in this study. We utilized glucose consumption, cell migration, and ELISA assay kits to investigate the function of GC. To understand its mechanism, we employed quantitative PCR (qPCR), western blot, and m6A methylated RNA immunoprecipitation assay. FKFB3 protein expression levels in patients with gastric cancer were increased. The induction of PFKFB3 mRNA expression levels in patients with gastric cancer or gastric cancer cell lines. Gastric cancer patients with high PFKFB3 expression had a lower survival rate. PFKFB3 high expression possessed the probability of pathological stage, lymph node metastasis or distant metastasis in patients with gastric cancer. PFKFB3 upregulation promoted cancer progression and Warburg effect progression of gastric cancer. PFKFB3 upregulation reduced pyroptosis and suppressed nucleotidebinding domain, leucinerich repeat containing protein 3-induced pyroptosis of gastric cancer. M6A-forming enzyme methyltransferase-like 3 increased PFKFB3 stability. Taken together, the M6A-forming enzyme methyltransferase-like 3 increased PFKFB3 stability and reduced pyroptosis in the model of gastric cancer through the Warburg effect. The PFKFB3 gene represents a potential therapeutic strategy for the treatment of gastric cancer.

Malignant gastrointestinal neuroectodermal tumor: a case report and literature review.

Introduction and importance: A malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare primary malignant mesenchymal tumor of the gastrointestinal tract characterized by EWSR1 gene rearrangement. An optimal systemic treatment strategy for advanced/recurrent GNET has not yet been identified. Case presentation: A 24-year-old male patient was hospitalized with abdominal pain and underwent two operations for a tumor in his small intestine. Immunohistochemistry (IHC) showed strong expression of S-100 protein and SOX 10. Fluorescence in situ hybridization analysis and next-generation sequencing analysis indicated that there were EWSR gene rearrangements and the presence of EWSR-ATP1 gene fusions, respectively. The diagnosis of GNET in the small intestine was confirmed by pathology. The young patient received the fifth-line of apatinib mesylate and the sixth-line of apatinib combined with temozolomide. The two apatinib-containing regimens showed stable disease and progression-free survival of 4.7 months and 3.1 months with single-agent apatinib or apatinib combined with temozolomide, respectively. Clinical discussion: To our best knowledge, this is the first report of malignant GNET treated with apatinib and temozolomide. Apatinib-containing regimens might has antineoplastic activity against GNET. The authors reviewed the relevant reports of previous GNET treatment, summarized the clinicopathological characteristics of GNET, and found that there are no reports of apatinib for backline treatment of GNET. Conclusion: Containing apatinib may provide an additional treatment option for patients with chemotherapy-resistant GNET tumors.