Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU.

Pharmacological characterization of a novel metal-based proteasome inhibitor Na-AuPT for cancer treatment.

The ubiquitin-proteasome system (UPS) is essential for maintaining cell homeostasis by orchestrating the protein degradation, but is impaired in various diseases, including cancers. Several proteasome inhibitors, such as bortezomib, are currently used in cancer treatment, but associated toxicity limits their widespread application. Recently metal complex-based drugs have attracted great attention in tumor therapy; however, their application is hindered by low water-solubility and poor absorbency.

STING1 in sepsis: Mechanisms, functions, and implications.

Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a dysregulated host immune response to infection, which can eventually lead to multiple organ failure and even death. As an adaptor transporter between the endoplasmic reticulum and Golgi apparatus, stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173) has been found to play a vital role at the intersection of innate immunity, inflammation, autophagy, and cell death in response to invading microbial pathogens or endogenous host damage.

Exosomal miR-107 antagonizes profibrotic phenotypes of pericytes by targeting a pathway involving HIF-1/Notch1/PDGFR/YAP1/Twist1 axis in vitro.

Microvascular pericytes have been demonstrated as an origin for myofibroblasts that produce excessive extracellular matrix (ECM) proteins such as α-smooth muscle actin (α-SMA) and type I collagen (ColIA1) and contribute to pulmonary fibrosis (PF). However, the signaling mechanism responsible for ECM production within pericytes is poorly understood. In this study, we examined exosomal miR-107 in the fibrotic phenotypes of pericytes and the pathogenesis of PF.

Digital gene expression profiling analysis of childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most commonly diagnosed malignancy in children. It is a heterogeneous disease, and is determined by multiple gene alterations and chromosomal rearrangements. To improve current understanding of the underlying molecular mechanisms of ALL, the present study profiled genome‑wide digital gene expression (DGE) in a population of children with ALL in China.

Potential role of High mobility group box 1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is characterized as a typical inflammation-related carcinoma. High mobility group box protein 1 (HMGB1), a non-histone DNA-binding protein, is identified as a potent proinflammatory mediator when presents extracellularly. Recently, a growing body of evidence indicates that HMGB1 plays a potential role in HCC, but many questions remain unanswered about the relationship between HMGB1 and HCC formation and development.

The role of HMGB1-RAGE axis in migration and invasion of hepatocellular carcinoma cell lines.

High mobility group protein box1 (HMGB1) and its receptor-receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells.

The Role of receptor for Advanced Glycation End Products (RAGE) in the proliferation of hepatocellular carcinoma.

The receptor for advanced glycation end products (RAGE) is oncogenic and overexpressed in human cancers, but its role in hepatocellular carcinoma remains unclear. Here we demonstrated that RAGE is overexpressed in primary hepatocellular carcinoma (PHC) compared to adjacent para-neoplastic liver samples. Serum endogenous secretory RAGE levels were also increased in PHC patients (p < 0.

WAVE1 regulates P-glycoprotein expression via Ezrin in leukemia cells.

For children with acute myeloblastic leukemia (AML), multidrug resistance (MDR) reduces treatment effectiveness, and often leads to poor patient survival. While a number of factors have been described that affect MDR, the mechanisms underlying this effect remain unclear. In this study, the role of WAVE1 in MDR was investigated.

[Enhancive effect of HMGB1 gene silence on adriamycin-induced apoptosis in K562/A02 drug resistance leukemia cells].

Objective: To investigate the effect of high mobility group boxl (HMGBI) gene silence on adriamycin (ADM)-induced apoptosis in K562/A02 drug resistance leukemia cells.

Methods: K562/ A02 cells were transient transfected with HMGB1- small interference RNA(siRNA) vector, and the levels of HMGB1 gene differential expression pre-and post-transfection were measured by RT-PCR and Western blotting. 50% inhibition concentration (IC50) of ADM on K562/A02 was determined by WST-8 assay.

[Expression of high mobility group box chromosomal protein 1 in peripheral blood of patients with rheumatoid arthritis].

Objective: To investigate the mRNA and protein expression of high mobility group box chromosomal protein 1 (HMGB1) in peripheral blood mononuclear cells (PBMCs) and serum.

Methods: Levels of HMGB1mRNA were detected with reverse transcription polymerase chain reaction (RT-PCR) in PBMC and levels of HMGB1 protein in PBMC and plasm were measured with Western blot in 38 patients with active rheumatoid arthritis (RA), 24 with inactive RA and 20 healthy controls. Ficoll density gradient centrifugation was used to separate PBMCs from peripheral blood.

[High mobility group box 1 is increased in children with acute lymphocytic leukemia and stimulates the release of tumor necrosis factor-alpha in leukemic cell].

Objective: Cytokine mediated cell immunity is the main mode of anti-tumor immunity in organism, and the disequilibrium of cytokine network is the main cause of tumor cells escaping immunologic surveillance. High mobility group box 1 (HMGB1), a nuclear protein, has recently been identified as an important mediator of local and systemic inflammatory diseases when released into the extracellular milieu. In the present study, the investigators explored the clinical significance of alteration in the serum levels of HMGB1 in childhood acute lymphocytic leukemia (ALL) and the mechanism of HMGB1-induced tumor necrosis factor (TNF)-alpha secretion in leukemic cells.

[Significance of heat shock protein 70 in cerebrospinal fluid in differential diagnosis of central nervous system infection in children].

Objective: To investigate the diagnostic value of heat shock protein 70 (HSP70) in central nervous system infection (CNSI) in children.

Methods: The level of HSP70 in the cerebrospinal fluid (CSF) was determined in children with CNSI of different etiology. The concentration of HSP70 was determined in the CSF of 104 children, among them 13 patients had purulent meningitis (PM), 38 patients had acute viral meningitis (VM), 7 patients had tuberculous meningitis (TM), and 46 with no CNSI to serve as controls.

[Heat shock pretreatment in inhibiting myocardical apoptosis induced by ischemia-reperfusion and its mechanism].

Objective: To explore the mechanisms of myocardial apoptosis during myocardial ischemia-reperfusion injury and to further clarify the molecular mechanisms by which heat shock pretreatment in inhibiting myocardial apoptosis induced by ischemia-reperfusion injury.

Methods: Myocardial ischemia-reperfusion injury was induced by the occlusion of left anterior descending branch of the coronary artery. Apoptosis was evaluated by DNA laddering assay and the activities of caspase 3, 8, or 9 was measured with Caspase Colorimetric Assay Kit.

[Effect of heat shock response on the cleavage of nucleolin induced by oxidative stress].

Objective: To observe the cleavage of nucleolin (C23) during apoptosis induced by oxidative stress and to clarify the effect of heat shock response (HSR) on the cleavage of nucleolin and its possible molecular mechanism.

Methods: We added 0.5 mmol/L peroxide hydrogen (H2O2 ) into cultured cells to mimic oxidative stress.