RESUMO
BACKGROUND: Breast cancer is notorious for its increasing incidence for decades. Ascending evidence has demonstrated that translocase of inner mitochondrial membrane (TIMM) proteins play vital roles in progression of several types of human cancer. However, the biological behaviors and molecular mechanisms of TIMM8A in breast cancer remain not fully illustrated. METHODS: Pan-cancer analysis was firstly performed for TIMM8A's expression and prognosis by Oncomine database. Subsequently, TIMM8A-related noncoding RNAs (ncRNAs) were identified by a series of bioinformatics analyses and dual-luciferase reporter assay, including expression analysis, correlation analysis, and survival analysis. Moreover, the effect of TIMM8A on breast cancer proliferation and apoptosis was evaluated in vitro by CCK-8 assays, EdU cell proliferation assays, JC-1 mitochondrial membrane potential detection assays and Western blot assays and the in vivo effect was revealed through a patient-derived xenograft mouse model. RESULTS: We found that TIMM8A showed higher expression level in breast cancer and the higher TIMM8A mRNA expression group had a poorer prognosis than the lower TIMM8A group. hsa-circ-0107314/hsa-circ-0021867/hsa-circ-0122013 might be the three most potential upstream circRNAs of hsa-miR-34c-5p/hsa-miR-449a-TIMM8A axis in breast cancer. TIMM8A promotes proliferation of breast cancer cells in vitro and tumor growth in vivo. CONCLUSION: Our results confirmed that ncRNAs-mediated upregulation of TIMM8A correlated with poor prognosis and act as an oncogene in breast cancer.
RESUMO
Cotton fibre is the most important source for natural textiles. The secondary cell walls (SCWs) of mature cotton fibres contain the highest proportion of cellulose content (> 90%) in any plant. The onset and progression of SCW cellulose synthesis need to be tightly controlled to balance fibre elongation and cell wall deposition. However, regulatory mechanisms that control cellulose synthesis during cotton fibre growth remain elusive. Here, we conducted genetic and functional analyses demonstrating that the R2R3-MYB GhMYB7 controls cotton fibre cellulose synthesis. Overexpression of GhMYB7 in cotton sped up SCW cellulose biosynthesis in fibre cells, and led to shorter fibres with thicker walls. By contrast, RNA interference (RNAi) silencing of GhMYB7 delayed fibre SCW cellulose synthesis and resulted in elongated fibres with thinner walls. Furthermore, we demonstrated that GhMYB7 regulated cotton fibre SCW cellulose synthases by directly binding to three distinct cis-elements in the respective GhCesA4, GhCesA7 and GhCesA8 promoters. We found that this regulatory mechanism of cellulose synthesis was 'hi-jacked' also by other GhMYBs. Together, our findings uncover a hitherto-unknown mechanism that cotton fibre employs to regulate SCW cellulose synthesis. Our results also provide a strategy for genetic improvement of SCW thickness of cotton fibre.
Assuntos
Celulose , Fibra de Algodão , Parede Celular/metabolismo , Celulose/metabolismo , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Gossypium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismoRESUMO
As an asphalt modifier, waste battery powder (WBP) has been proven to be possible. This paper studies the modification effect of WBP on asphalt. The Flight Test Instrumentation Requirements (FITR) of WBP, Dynamic Shear Rheology (DSR) test, and Full Section Fracture Energy Test (FSFET) of asphalt are carried out. The high-temperature rheological properties and low-temperature properties of WBP modified asphalt are analyzed. The high-temperature stability, low-temperature crack resistance and water stability of WBP modified asphalt mixture are tested. The research results show that the modification of asphalt by WBP is essentially physical modification but the mixing of WBP has a certain enhancement effect on the bond energy of the methylene group, which is helpful to improve the technical performance of modified asphalt. The proportion of elastic components in asphalt can be significantly increased by adding WBP, thus enhancing the deformation resistance of asphalt under high-temperature conditions. The dynamic shear modulus of 10% waste battery powder is about 1.5-2.0 times that of 0% waste battery powder. The mixing of WBP reduces the proportion of viscous components in asphalt which is unfavorable to the crack resistance under low temperatures. The greater the amount of WBP, the smaller the fracture energy density, the content of WBP is 6% and 10%, the fracture energy density is about 60-80% and 40-60% of the original asphalt, and the low temperature cracking resistance of asphalt decreases. The modification effect of WBP on asphalt is much lower than that of SBS.
RESUMO
BACKGROUND: Camrelizumab, as a PD-1 inhibitor on the market recently, presents favorable therapeutic efficacy in several advanced cancers, while its application in metastatic gastric cancer (mGC) lacks data. This study aimed to assess treatment response, survival profile, and adverse events of camrelizumab plus apatinib regimen as third-line treatment in mGC patients. METHODS: Nineteen mGC patients who received camrelizumab plus apatinib as third-line treatment were analyzed in this observational study. Subsequently, treatment response and adverse events were documented, then progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: No (0.0%) patient achieved complete response; 5 (26.3%) patients achieved partial response; 8 (42.1%) patients had stable disease; 6 (31.6%) patients had progressive disease, resulting in objective response rate and disease control rate of 26.3% and 68.4%, respectively. Meanwhile, the median PFS and OS were 7.0 (95%CI: 2.9-11.0) months and 10.0 (95%CI: 7.4-12.6) months, accordingly. Besides, multiple metastases linked with worse PFS (P = 0.029) and OS (P = 0.021); Eastern Cooperative Oncology Group performance status (ECOG PS) score 1 (vs. 0) related to shorter OS (P = 0.030). Worth noting, the common adverse events were fatigue (42.1%), anemia (42.1%), neutropenia (42.1%), leukopenia (36.8%), pruritus (31.6%), proteinuria (31.6%), nausea and vomiting (31.6%), reactive capillary hemangioma (31.6%) and thrombocytopenia (31.6%). Meanwhile, grade 3-4 adverse events only included: thrombocytopenia (5.3%), hypertension (5.3%), and proteinuria (5.3%). CONCLUSION: Camrelizumab plus apatinib as third-line treatment achieves satisfactory therapeutic efficacy and survival profile with generally manageable adverse events in mGC patients.
Assuntos
Antineoplásicos , Neoplasias Gástricas , Trombocitopenia , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Humanos , Proteinúria/induzido quimicamente , Proteinúria/tratamento farmacológico , Piridinas , Neoplasias Gástricas/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológicoRESUMO
The objective of this study is to verify the feasibility of using biochar made from crop straw as a bitumen additive to improve some properties of bitumen. The differences between crop straw biochar prepared in a laboratory and commercial charcoal were investigated through scanning electron microscopy and laser particle size analyses. Furthermore, biochar-modified asphalt was prepared using the high-speed shear method, and the penetration, softening point, ductility at 15°C, and apparent viscosity of the asphalt binder with 6% biochar were measured at 120, 135, 150, 160, and 175°C. It was found that both the crop straw biochar and the commercial charcoal consist mainly of C, O, Si, and K, but the C content of crop straw biochar is slightly higher than that of commercial charcoal. The particle size of biochar is smaller than that of commercial charcoal, while the specific surface area is larger. It was determined that the addition of crop straw biochar significantly improved the high-temperature performance of asphalt, and that biochar and commercial charcoal have a similar influence on the high temperature performance of asphalt.
Assuntos
Agricultura/métodos , Carvão Vegetal/química , Produtos Agrícolas/química , Hidrocarbonetos/química , Temperatura Alta , Solo/químicaRESUMO
OBJECTIVE: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. METHODS: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. RESULTS: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5µM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. CONCLUSION: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.
Assuntos
Antineoplásicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Compostos Organoplatínicos/farmacologia , Piridinas/farmacologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Modelos Moleculares , Compostos Organoplatínicos/química , Piridinas/químicaRESUMO
PURPOSE: The identification of prognostic markers for colorectal cancer (CRC) is needed for clinical practice. Fructose-bisphosphate aldolase A (ALDOA) and DEAD box p68 RNA helicase (DDX5) are commonly overexpressed in cancer and correlate with tumorigenesis. However, association between expression of ALDOA and DDX5, and CRC outcome has not been reported. PATIENTS AND METHODS: We used 141 formalin-fixed paraffin-embedded (FFPE) specimens collected from 105 patients with CRC treated at the Affiliated Hospital of Guilin Medical University and the People's Hospital of Liuzhou. We performed tissue microarray based immunohistochemistry to explore expression features and prognostic value (overall survival, OS; disease-free survival, [DFS]) of ALDOA and DDX5 in CRC tissues. The prognostic values were evaluated using Kaplan-Meier analysis, and Cox regression analyses. RESULTS: ALDOA and DDX5 were highly expressed in CRC tissues and liver metastatic CRC tissues compared with normal glandular epithelium tissues (all p<0.05). Interestingly, primary CRC tissues highly expressing ALDOA or DDX5 had poor outcome (p<0.0001 for both OS and DFS for ALDOA; p=0.001 for OS; and p=0.011 for DFS for DDX5) compared with patients who had low expression of those proteins. Furthermore, multivariate Cox analysis showed that ALDOA/DDX5 combination was an independent risk factor for OS and ALDOA was an independent risk factor for DFS. CONCLUSION: High levels of ALDOA and DDX5 contribute to the aggressiveness and poor prognosis of CRC. ALDOA/DDX5 expression could be a biomarkers for the prognosis of CRC.