Effects of hexavalent chromium on mitochondria and their implications in carcinogenesis.

Hexavalent chromium (Cr(VI)) is a well-known occupational and environmental human carcinogen. The cellular effect of Cr(VI) is complex and often nonspecific due to its ability to modulate multiple cellular targets. The toxicity of Cr(VI) is strongly linked to the generation of reactive oxygen species (ROS) during its reduction process.

Effect of Gene 33/Mig6/ERRFI1 on hexavalent chromium-induced transformation of human bronchial epithelial cells depends on the length of exposure.

Hexavalent chromium (Cr(VI)) compounds are environmental and occupational lung carcinogens. The present study followed the chronic effect of Cr(VI) on the neoplastic transformation of BEAS-2B lung bronchial epithelial cells with or without deletion of Gene 33 (Mig6, EFFRI1), a multifunctional adaptor protein. We find that Gene 33-deleted cells exhibit increased anchorage-independent growth compared to control cells after transformed by 8-week but not 24-week Cr(VI) exposure.

Immune regulatory functions of biologically active proteins from edible fungi.

Proteins from edible mushrooms have a variety of biological activities. Here, thirteen precious edible mushrooms such as , , and and nine common edible mushrooms such as , , and , etc., from which their proteins were extracted, their composition analyzed and their immunomodulatory activity assessed.

Gene 33/Mig6/ERRFI1, an Adapter Protein with Complex Functions in Cell Biology and Human Diseases.

Gene 33 (also named Mig6, RALT, and ERRFI1) is an adapter/scaffold protein with a calculated molecular weight of about 50 kD. It contains multiple domains known to mediate protein-protein interaction, suggesting that it has the potential to interact with many cellular partners and have multiple cellular functions. The research over the last two decades has confirmed that it indeed regulates multiple cell signaling pathways and is involved in many pathophysiological processes.

Regulation of the SIAH2-HIF-1 Axis by Protein Kinases and Its Implication in Cancer Therapy.

The cellular response to hypoxia is a key biological process that facilitates adaptation of cells to oxygen deprivation (hypoxia). This process is critical for cancer cells to adapt to the hypoxic tumor microenvironment resulting from rapid tumor growth. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor and a master regulator of the cellular response to hypoxia.

Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer.

Our previous studies have demonstrated that XIAP promotes bladder cancer metastasis through upregulating RhoGDIβ/MMP-2 pathway. However, the molecular mechanisms leading to the XIAP upregulation was unclear. In current studies, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BCs, and in mouse invasive BCs.

[Multifunctional Cervical Health Care Pillow].

Cervical spondylosis is due to degenerative cervical disc and its stimulation or oppression of the adjacent nerves, spinal cord, spinal artery and other tissue caused by clinical symptoms. The cervical spine is an anatomical structure with activity, while the pillow has a certain plastic fixation effect on the cervical spine anatomy. Therefore, the pillow not only plays a health role in the cervical spine, but also plays an important role in restoring the normal physiological curvature of the cervical spine.

[Development of Software System for Artificial Joint Biomechanics].

In the research of artificial joint biomechanics, it is a common method in the world to evaluate the biomechanical properties of the implanted fixtures through experiments . The domestic research started late, and the corresponding testing software were lacking. There is still no special software.

[Hardware System for the Test of Artificial Joint Biomechanics].

In the research of artificial joint biomechanics, it is a common method in the world to evaluate the biomechanical properties of the implanted fixtures through experiments . The domestic research started late, and the corresponding testing methods were lacking. There is still no unified standard.

Melatonin protects mouse spermatogonial stem cells against hexavalent chromium-induced apoptosis and epigenetic histone modification.

Given the potential biological functions of spermatogonial stem cells (SSCs) in spermatogenesis and in delivering parental genetic information to the next generation, how these cells respond to environmental toxins and carcinogens should be investigated. We examined the toxic effect of hexavalent chromium (Cr(VI)) on global histone modifications and apoptotic signaling pathways in SSCs. We determined the effect of melatonin, one of the most powerful endogenous free radical scavengers and wide-spectrum antioxidants, in protecting SSCs from Cr(VI)-induced apoptosis and global histone modification by Western blot analysis.

Transcription factors and stress response gene alterations in human keratinocytes following Solar Simulated Ultra Violet Radiation.

Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging and carcinogenesis. However, genes and pathways altered by solar-simulated UVR (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to ssUVR.

Polo-like kinase 3, hypoxic responses, and tumorigenesis.

The cellular hypoxic response contributes to cell transformation and tumor progression. Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor that mediates transcription of genes whose products are essential for cellular adaptation to hypoxia. The activity of HIF-1 is largely regulated by the abundance of its alpha subunit (HIF-1α), which is primarily regulated by an oxygen-dependent and ubiquitin/proteasome-mediated degradation process.

Nuclear Gene 33/Mig6 regulates the DNA damage response through an ATM serine/threonine kinase-dependent mechanism.

Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium (Cr(VI)), but the molecular mechanism remains unknown. Here we show that ectopic expression of Gene 33 triggers DDR in an ATM serine/threonine kinase (ATM)-dependent fashion and through pathways dependent or not dependent on ABL proto-oncogene 1 non-receptor tyrosine kinase (c-Abl).

Single-cell RNA sequencing reveals an altered gene expression pattern as a result of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to hexavalent chromium in human lung epithelial cells.

Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently reported that depletion of this protein promotes lung epithelial cell transformation induced by hexavalent chromium [Cr(VI)]. However, the early molecular events that mediate this process are not clear.

Mutual regulation between Polo-like kinase 3 and SIAH2 E3 ubiquitin ligase defines a regulatory network that fine-tunes the cellular response to hypoxia and nickel.

Elevated cellular response to hypoxia, which contributes to cell transformation and tumor progression, is a prominent feature of malignant cells in solid tumors. Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase known to inhibit the cellular response to hypoxia and tumorigenesis. Nickel compounds are well-established human carcinogens that induce tumorigenesis partly through their hypoxia-mimicking effects.

Gene 33/Mig6 inhibits hexavalent chromium-induced DNA damage and cell transformation in human lung epithelial cells.

Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis.

Expression of the p12 subunit of human DNA polymerase δ (Pol δ), CDK inhibitor p21(WAF1), Cdt1, cyclin A, PCNA and Ki-67 in relation to DNA replication in individual cells.

We recently reported that the p12 subunit of human DNA polymerase δ (Pol δ4) is degraded by CRL4(Cdt2) which regulates the licensing factor Cdt1 and p21(WAF1) during the G1 to S transition. Presently, we performed multiparameter laser scanning cytometric analyses of changes in levels of p12, Cdt1 and p21(WAF1), detected immunocytochemically in individual cells, vis-à-vis the initiation and completion of DNA replication. The latter was assessed by pulse-labeling A549 cells with the DNA precursor ethynyl-2'-deoxyribose (EdU).

Arsenic induces polyadenylation of canonical histone mRNA by down-regulating stem-loop-binding protein gene expression.

The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3'-end. Instead, the histone mRNAs display a stem-loop structure at their 3'-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism.

Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock.

Objective: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury.

Background: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied.

Methods: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate.

Differential responses to genotoxic agents between induced pluripotent stem cells and tumor cell lines.

Given potential values of induced pluripotent stem (iPS) cells in basic biomedical research and regenerative medicine, it is important to understand how these cells regulate their genome stability in response to environmental toxins and carcinogens. The present study characterized the effect of Cr(VI), a well-known genotoxic agent and environmental carcinogen, on major molecular components of DNA damage response pathways in human iPS cells. We compared the effect of Cr(VI) on human iPS cells with two established cell lines, Tera-1 (teratoma origin) and BEAS-2B (lung epithelial origin).

Enhancing bone marrow regeneration by SALL4 protein.

Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient's morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro.

Nuclear protein IK undergoes dynamic subcellular translocation and forms unique nuclear bodies during the cell cycle.

IK is a nuclear protein containing a unique domain named RED due to the presence of a repetitive arginine (R), aspartic (E), and glutamic acid (D) sequence. To date, the function of this protein remains largely unknown despite of a couple of previous studies in the literature. Here we report that depletion of IK via RNA interference results in mitotic arrest.

Does recombinant factor XIII eliminate early manifestations of multiple-organ injury after experimental burn similarly to gut ischemia-reperfusion injury or trauma-hemorrhagic shock?

The authors have previously shown that recombinant factor XIII (rFXIII) eliminates early manifestations of multiple-organ injury caused by experimental superior mesenteric artery occlusion or trauma-hemorrhagic shock. The aim of the present study was to test the hypothesis that rFXIII provides similar protective effect in experimental burn injury. Rats were randomly divided into five groups (eight animals per group): group 1: burn + placebo treatment; group 2: burn + rFXIII pretreatment; group 3: burn + rFXIII treatment; group 4: sham burn + placebo treatment, and group 5: sham burn + rFXIII treatment.

Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock.

We tested if vagus nerve stimulation (VNS) would prevent gut injury, mesenteric lymph toxicity, and systemic multiple organ dysfunction syndrome following trauma-hemorrhagic shock (T/HS). Four groups of experiments were performed. The first tested whether VNS (5 V for 10 min) would protect against T/HS-induced increases in gut and lung permeability as well as neutrophil priming.

Roles of Polo-like kinase 3 in suppressing tumor angiogenesis.

Angiogenesis is essential for promoting growth and metastasis of solid tumors by ensuring blood supply to the tumor mass. Targeting angiogenesis is therefore an attractive approach to therapeutic intervention of cancer. Tumor angiogenesis is a process that is controlled by a complex network of molecular components including sensors, signaling transducers, and effectors, leading to cellular responses under hypoxic conditions.