Changes in DNA methylation patterns, in which DNA methyltransferases such as DNA methyltransferase 3 alpha (DNMT3a) play important roles, are closely related to the occurrence and development of tumours. However, the role and mechanism of DNMT3a in lung adenocarcinoma (LUAD) remain unknown. The aim of this study was to investigate the potential effect of DNMT3a on LUAD cell proliferation and metastasis and explore the underlying molecular mechanism.
View Article and Find Full Text PDFBackground And Objective: Lung cancer, mainly non-small cell lung cancer (NSCLC), is a serious threat to human life. In particular, the prognosis for advanced patients is poor, with the 5-year survival rate being exceedingly low. In recent years, immune checkpoint inhibition has changed the pattern of the treatment of a variety of cancers, including lung cancer; however, not all patients can benefit from immunotherapy, and thus finding the right biomarkers is particularly important for guiding precise treatment.
View Article and Find Full Text PDFCancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC.
View Article and Find Full Text PDFBackground: Hyper progressive disease (HPD) describes the phenomenon that patients can't benefit from immunotherapy but cause rapid tumor progression. HPD is a particular phenomenon in immunotherapy but lacks prediction methods. Our study aims to screen the factors that may forecast HPD and provide a predictive model for risky stratifying.
View Article and Find Full Text PDFCarbon nanodots (CNDs) which demonstrate concentration-dependent emission and have a photoluminescence quantum yield of 45% were designed. Transparent CND-containing composite films (CND-films), obtained by combining the CNDs with polyvinyl alcohol in different proportions, were shown to block the UV component of sunlight. Whereas the pure PVA film could not block UV light, the ability of CND-films to block UV light could be adjusted by altering the proportion of CNDs in the film.
View Article and Find Full Text PDFThe concept of targeting cholesterol metabolism to treat cancer has been widely tested in clinics, but the benefits are modest, calling for a complete understanding of cholesterol metabolism in intratumoral cells. We analyze the cholesterol atlas in the tumor microenvironment and find that intratumoral T cells have cholesterol deficiency, while immunosuppressive myeloid cells and tumor cells display cholesterol abundance. Low cholesterol levels inhibit T cell proliferation and cause autophagy-mediated apoptosis, particularly for cytotoxic T cells.
View Article and Find Full Text PDFImportance: Both pembrolizumab and sintilimab have been approved by the Chinese State Drug Administration (NMPA) for the first-line treatment of patients with advanced squamous lung cancer. The differences of the two drugs in efficacy and safety are unclear.
Objectives: To compare the real-world efficacy and safety of first-line treatments in patients with advanced squamous lung cancer.
Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, following which phenotypic traits of malignancy were assessed . Ruxolitinib was used as a surrogate to compare the effects of ENC1 expression and silencing on the JAK-STAT-AKT pathway.
View Article and Find Full Text PDFThere is a lack of useful biomarkers for predicting the efficacy of anti-programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti-PD-1 regimens were retrospectively analyzed.
View Article and Find Full Text PDFSirtuins (SIRTs) are members of the silent information regulator-2 family. They are a conserved family of nicotinamide adenine dinucleotide-dependent protein lysine deacylases. SIRTS are involved in intricate cellular processes.
View Article and Find Full Text PDFMitochondria-localized sirtuin 4 (SIRT4) is associated with malignant phenotypes in colorectal cancer (CRC). However, the molecular mechanisms that drive SIRT4-mediated carcinogenesis are unclear. Initially, we confirmed expression of SIRT4 in CRC through public database and in CRC patient tissues using quantitative real-time reverse transcription PCR.
View Article and Find Full Text PDFThe present research is aimed to elucidate the expression patterns of miR-424-5p and its role in tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). Both starBase and TCGA were utilized to assess miR-424-5p expression status in ESCC. The endogenous mRNA expression levels of miR-424-5p in ESCC and normal esophagus cell lines were detected by qRT-PCR.
View Article and Find Full Text PDFPurpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC.
Materials And Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study.
Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer. The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models.
View Article and Find Full Text PDFWnt4 is a secreted growth factor associated with renal tubulogenesis. Our previous studies identified that renal and urinary Wnt4 are upregulated following ischemia-reperfusion injury in mice, but the roles of Wnt4 in other forms of acute kidney injury (AKI) remain unclear. Here, we investigated the changes in Wnt4 expression using a cisplatin-induced AKI model.
View Article and Find Full Text PDFT-cell receptor-CD3 complex (TCR) is a versatile signaling machine that can initiate antigen-specific immune responses based on various biochemical changes of CD3 cytoplasmic domains, but the underlying structural basis remains elusive. Here we developed biophysical approaches to study the conformational dynamics of CD3ε cytoplasmic domain (CD3ε). At the single-molecule level, we found that CD3ε could have multiple conformational states with different openness of three functional motifs, i.
View Article and Find Full Text PDFCD8(+) T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment. Reactivating the cytotoxicity of CD8(+) T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8(+) T cells can be potentiated by modulating cholesterol metabolism.
View Article and Find Full Text PDFJ Recept Signal Transduct Res
August 2016
Background: Osteoporosis is a systemic skeletal disease with the high incidence, serious complications, financial burden, and heavily decrease in living quality.
Methods: Proliferation of osteoblast was tested by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, alkaline phosphatase (ALP) activity of osteoblasts was tested by ALP REAGENT, Calcium level was determined by a colorimetric assay, mRNA expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1 (PDK1), Akt, Caspase-3, Caspase-7, Caspase-9, osteocalcin (OCN), Osterix and Runx2 of osteoblasts was tested by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR), and protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt was measured by Western Blot analysis.
Results: In osteoporosis model rats, it found that mRNA expression of PI3K, PDK1 and Akt showed no changes while protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt in bone tissue was decreased dramatically.
Zhongguo Zhong Xi Yi Jie He Za Zhi
April 2015
Objective: To observe the effect of Shen warming Pi strengthening method on expressions of serum T cell subsets (C045+%, C03+%, and C04 +/COB+) in diarrhea-predominant irritable bowel syndrome (IBS-0) rats. Methods An IBS-0 rat model was established referring to AL-Chaer's modeling method combined with tail clamp and intragastric administration of sanna leaf. After modeling 30 SO rats were randomly divided into 6 groups according to random digit table, i.
View Article and Find Full Text PDFZhongguo Zhong Xi Yi Jie He Za Zhi
February 2014
Objective: IBS-D rat model was established to assess the effect of Shen warming Pi strengthening method (SWPSM) for intervening diarrhea-predominant irritable bowel syndrome (IBS-D) by observing rats' general state, stool properties, AWR ranking, and histopathological changes.
Methods: Totally 72 rats were randomly divided into 6 groups, i.e.
Objective: To observe the curative effect of a recipe for warming the kidney and fortifying the spleen on diarrhea-predominant irritable bowel syndrome (IBS-D).
Methods: This multi-center, double-blind, randomized, and controlled trial included 240 patients that met the inclusion criterion and were then divided into two groups of 120. Patients in the treatment group (group A) took modified Sishen Wan orally for warming the kidney and fortifying the spleen and patients in the control group (group B) took a placebo, Chao Maiya, for 4 weeks.