During hair follicle regeneration, hair follicle stem cells (HFSCs) are regulated by signals from dermal papilla cells (DPCs). Previously we found that Tcf4 could promote the proliferation of DPCs. ...In this study, we focused on whether and how the biological properties of Tcf4-induced DPCs were regulated by Twist1.
Twist1 was overexpressed or knocked down in DPCs following different adenovirus or lentivirus infection. Phase-contrast microscopy was used to observe the agglutinative growth of DPCs. The CCK-8 assay was used to test the proliferation of DPCs. Western blot and qPCR experiments were used to determine the expression of HGF, IGF-1, VEGF, c-myc, survivin, and CyclinD1 in DPCs. ELISAs were used to test the growth factors secreted by DPCs. Conditional medium culture was used to detect the inductive ability of DPCs. Co-immunoprecipitation and immunofluorescence were used to test the binding of Twist1, Tcf4, and β-catenin in DPCs. Immunofluorescence was also used to test the expression of Twist1, Tcf4, and KRT15 in hair follicles.
Twist1 induced DPC agglutinative growth and proliferation. Twist1 upregulated the expression of downstream target genes downstream of Tcf4, c-myc, survivin, in Tcf4-induced DPCs, as well as the expression and secretion of growth factors HGF, IGF-1, VEGF, which had the ability to induce hair follicle growth. The conditional medium from Twist1-treated DPCs increased the expression of KRT40 and MSX2 in HaCaT cells. Twist1 and Tcf4 co-localized in DPCs both
and
Anti-Twist1 precipitated Tcf4 and β-catenin.
These results indicate that Tcf4 and Twist1 play a synergistic role in regulating the hair follicle induction ability of DPCs. Twist1 functions by forming a ternary complex with Tcf4 and β-catenin. Thus, we report new data that elucidate whether and how Twist1 regulates some biological properties of DPCs.
Dermal papilla cells (DPCs) are important components of hair follicles and play a critical role in hair follicle development. However, the mechanisms by which DPCs induce hair follicle development ...remain unclear. In the present study, we identified the mitotic arrest deficient protein MAD2B as a modifier of DPCs. Overexpression of MAD2B inhibited DPC aggregative growth and proliferation induced by the Wnt signaling activator T cell factor 4 (TCF4), and decreased TCF4-induced expression and the release of hair growth-related cytokines, including hepatocyte growth factor, insulin-like growth factor-1, and vascular endothelial growth factor in DPCs. In contrast, knockdown of MAD2B promoted TCF4-induced DPC proliferation, but did not affect the expression and secretion of cytokines by TCF4-induced DPCs. These results suggest a functional antagonism between MAD2B and TCF4 in DPC-induced hair follicle development. Mechanistically, MAD2B physically interacted with TCF4 to repress TCF4 transcriptional activity via β-catenin mediation, leading to reduced β-catenin/TCF4-dependent transactivation and Wnt signaling activity. These results demonstrate, for the first time, that MAD2B plays a negative role in TCF4-induced DPC growth and proliferation.
Background
Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been ...observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive.
Aims
To investigate miR-98 expression and the biological functions in colon cancer progression.
Methods
miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples. miR-98 mimic or inhibitor was used to test the biological functions in SW480 and HCT116 cells, followed by cell proliferation assay, lactate production, glucose uptake, and cellular ATP levels assay and extracellular acidification rates measurement. Western blot and luciferase assay were used to identify the target of miR-98.
Results
miR-98 was significantly down-regulated in colon cancer tissues compared to adjacent colon tissues and acted as a suppressor for Warburg effect in cancer cells. miR-98 inhibited glycolysis by directly targeting hexokinase 2, or HK2, illustrating a novel pathway to mediate Warburg effect of cancer cells. In vitro experiments further indicated that HK2 was involved in miR-98-mediated suppression of glucose uptake, lactate production, and cell proliferation. In addition, we detected HK2 expression in colon cancer tissues and found that the expressions of miR-98 and HK2 were negatively correlated.
Conclusion
miR-98 acts as tumor suppressor gene and inhibits Warburg effect in colon cancer cells, which provided potential targets for clinical treatments.
Due to the increasingly urgent safety and energy density concerns of lithium-ion batteries, more and more attention has been attracted by the Li
7
La
3
Zr
2
O
12
(LLZO)-based solid electrolytes with ...high ion conductivity and chemical stability against Li-metal. However, to prepare the high-quality LLZO ceramic electrolyte with high-ion conductivity and density, there is still a big challenge of the serious “Li-loss” and the abnormal grain growth during the long-time high-temperature sintering process. A novel covered sintering method is put forward to prepare the high-quality Mo-doped LLZO (LLZMO) ceramic electrolyte. The sintering strategy effectively suppresses the Li-loss to obtain the LLZMO dense ceramics with cubic garnet phase and tight grain boundaries. The LLZMO ceramics sintered at lower temperature of 1050 °C for 2 h via the novel covered sintering exhibit high density (
ρ
r
= 92.3%) and high-ionic conductivity of 6.08 × 10
–4
S cm
−1
at 25 °C, which are close to those of LLZO-based ceramics prepared by hot pressing sintering, ultrafast high-temperature sintering (UHS). The novel covered sintering provides an energy-saving, low-cost and high-efficient strategy to prepare the high-quality LLZO-based ceramics electrolyte.
Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family that mediates the ubiquitin-proteasome system and regulates gene expression. It is a major oncogene in several cancers such as ...lung cancer and breast cancer, while the potential functions of UBE2T in gastric cancer (GC) remains largely unknown. Here, we identified the roles of UBE2T in GC progression and its potential to act as a prognostic marker of GC. Our data demonstrated that UBE2T was significantly upregulated in gastric cancer tissues, and the high expression of UBE2T was significantly correlated with poor differentiation, high T classification, and poor prognosis. In vitro experiments indicated that UBE2T promoted cell proliferation and inhibited cell cycle arrest. In addition, we observed that UBE2T modulated cell mobility by inducing epithelial-mesenchymal transition. Collectively, these findings suggest that UBE2T plays an important role in the tumorigenesis of gastric cancer and could act as a potential independent prognostic factor for cancer therapy.
Aim: To investigate the feasibility of assessing the ecacy of non-surgical treatment for gastric lymphoma using oral contrast-enhanced ultrasound (OCEUS) and double contrast-enhanced ultrasound ...(DCEUS). Material and methods: A total of 27 patients with gastric lymphoma treated nonoperatively were included in this retrospective study. The ecacy was evaluated using OCEUS and CT, respectively, and the results were tested for kappa concordance. Sixteen of the 27 patients underwent multiple DCEUS examinations before and after treatment. Micro-perfusion of the lesion in DCEUS is represented by the Echo Intensity Ratio (EIR), (echo intensity of the lymphoma lesion/echo intensity of the normal gastric wall), and one-way ANOVA was used to compare the differences between groups in EIR values before and after treatment. Results: OCEUS and CT were highly consistent in assessing the efficacy of gastric lymphoma, with a Kappa value of 0.758. During a median follow-up of 8.8 months, there was no statistical difference between the complete remission rate obtained by OCEUS and that obtained by endoscopic and CT (25.93% vs. 44.44%, p=0.154; 25.93% vs. 33.33%, p=0.766). There was also no statistical difference in the time to achieve complete remission using OCEUS assessment and endoscopy and CT (4.71±1.03 months vs. 6.01±2.14 months, p=0.088; 4.47±1.84 months vs. 6.01±2.14 months p=0.143). The difference in EIR between the groups before treat-ment and after different numbers of treatments was statistically signifficant (p<0.05), and post hoc analysis revealed this dif-ference as early as after the second treatment (p<0.05). Conclusions: Transabdominal OCEUS and CT are comparable in the assessment of gastric lymphoma treatment ecacy. DCEUS is a noninvasive, cost-effective, and widely available method for gastric lymphoma therapeutic effect evaluation. Therefore, transabdominal OCEUS and DCEUS have the potential to be used for the early assessment of the ecacy of the non-surgical treatment of gastric lymphoma
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