Acute lung injury ( ALI) and its most extreme form a-cute respiratory distress syndrome ( ARDS) are lung diseases with high morbidity and mortality. There is no effective therapeutic intervention until now for its complicated pathophysiologi-cal processes and sophisticated regulatory mechanism. Histone deacetylases (HDACs) are a family of proteins with deacetylase activity. Studies have shown that HDACs are involved in the pathophysiological processes of ALI/ARDS, including inflammatory responses,endothelial permeability,oxidative stresses,alveolar fluid clearance and lung tissue repairment. Simultaneously, the use of HDACs inhibitors (HDACIs) can interfere with ALI/ ARDS progression. In this review we describe and summarize the pathophysiological processes and the underlying mechanisms in ALI/ARDS regulated by HDACs and HDACIs in detail, in order to provide the basis for the clinical application of HDACs-targe- ted agents and indicate directions for future study.

Histone deacetylase 3 (HDAC3) plays an important role in chromatin remodeling, which in turn regulates gene transcription, so HDAC3 is involved in the pathophysiology of various diseases through epigenetic regulation. Organ ischemia-reperfusion injury (I R I) is a pathophysiological process that leads to the development of a variety of diseases such as delayed neuronal necrosis, irreversible shock, myocardial infarction, acute organ failure and organ transplant rejection. In this paper we review the pathophysiological function of HDAC3 and its role in the development of IRI in human parenchymal organs, and also explore the therapeutic value of HDAC3 in IRI.

As a pulmonary complication of diabetes, diabetic pulmonary fibrosis has gradually entered people's sight, but its mechanism is still poorly understood.This is the first systematic review of the mechanisms of autonomic neuropathy, pulmonary microangiopathy, accumulation of advanced glycosylation end products, oxidative stress, inflammation, epithelial-mesenchy- mal transition and endothelial-mesenchymal transition, cell se¬nescence and I)NA damage, etc.in diabetic pulmonary fibrosis.which aims to provide inquiring ideas for exploring the specific molecule mechanism and a reference for the development of ther¬apeutic drugs for diabetic pulmonary fibrosis.,,,,.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca
Adenosine Triphosphate ; Animals ; Antidepressive Agents/therapeutic use* ; Caloric Restriction ; Mice ; Mice, Knockout ; Prefrontal Cortex

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

Objective To investigate the effect of hypoxia inducible factor-1ɑknocked down by small interfering RNA ( siR-NA) on cell proliferation , apoptosis and apoptotic pathways of human Y-79 RB cells.Methods Cell proliferation , HIF-1ɑmRNA and protein levels were measured by MTT , RT-PCR and Western Blot on human Y-79 RB cells under both normoxic and hypoxic conditions , respectively .siRNA knockdown against HIF-1ɑwas carried out to suppress the expression of HIF-1ɑ.Cell apotosis was determined by double staining cells with the annexin V-FITC and PI.Caspase activity was assessed by the fluorometric assay .Biostatistical analyses were conducted with SPSS 16.0 software package.Results A multifold increase in HIF-1ɑmRNA and protein levels were observed af-ter cells were exposed to the hypoxic environment at 0 h,4 h,8 h and 12 h.Both mRNA and protein levels of HIF-1ɑwere attenuated or abolished by transfection with siRNA H IF-ɑunder normoxic and hypoxic conditions .Futhermore,knockdown of HIF-1ɑcould enhance hy-poxia-induced slight increase of Bax/Bcl-2 ratio and activate caspase-9 and caspase-3.Conclusion This study was able to show that a knockdown of HIF-1ɑby siRNAH IF-1ɑresulted in a decrease in proliferation and induction of apoptosis in human Y-79 RB cells under both normoxic and hypoxic conditions .HIF-1ɑexpression may be a promising strategy for the treatment of human RB in the future .

OBJECTIVESTo dynamically observe how glioma stem cells promote the tumor formation and angiogenesis, and to study the correlation between the distribution of glioma stem cells and microvessels within different growth stages of subcutaneous tumor.

METHODSStem cell medium culture and magnetic activated cell sorting were carried out to obtain CD133+ cells from C6 rat glioma cell line. Sprague Dawley (SD) rat ears model were established to observe glioma stem cells promoting blood vessel formation. Subcutaneous glioma model of C6 and immunohistochemical staining of hypoxia inducible factor-1α (HIF-1α) and CD133 were used to investigate the relationship between distribution of glioma stem cells and microvessels. Expressions of CD133 protein in each stage of the subcutaneous tumor were detected by Western blot.

RESULTSIsolation and identification of glioma stem cells deprived from C6 glioma cell line successfully, the establishment of ears model showed real-time dynamic observation of CD133+ cells involved in angiogenesis and tumor formation. SD rat model of subcutaneous glioma showed the initial of tumor formation, CD133+ cells scattered. With tumor growth, CD133+ cells began to tend to capillaries, in late distributed clusters in perivascular. Meanwhile as tumor growth, CD133 protein expression was gradually increased: the values of Western blot analysis of CD133 expression on 6, 9, 12, 15, 20 d were 0.208±0.004, 0.282±0.003, 0.360±0.004, 0.564±0.135, 0.756±0.007, the differences were significant between different groups (F=2601.681, P<0.01). At a high magnification, the CD133 scores with immunohistochemical staining on 6, 9, 12, 15 d were 0.8±0.4, 2.4±0.5, 4.0 ± 0.7, 6.0±0.7; HIF-1α scores were 0.8±0.4, 2.8±0.8, 5.0±0.7, 6.8±0.4. By Spearman rank correlation analysis found that the relationship between CD133 and HIF-1α expression was positively correlated (r=0.921, P<0.01).

CONCLUSIONSGlioma stem cells promote angiogenesis more than non-stem cells; HIF-1α and its downstream gene product might mediate the distribution of glioma stem cells around the perivascular.

Animals ; Cell Line, Tumor ; Glioma ; blood supply ; metabolism ; pathology ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Microvessels ; pathology ; Neoplasm Transplantation ; Neoplastic Stem Cells ; pathology ; Neovascularization, Pathologic ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of parathyroid hormone related protein (PTHrP) on proliferation of human osteoblasts (MG-63) under the circumstance of tension force in vitro.

METHODSAn apparatus was designed and fabricated by which force was loaded onto the cultured cells in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) was used for measuring the expression of PTHrP mRNA and c-fos mRNA. The effect of tension force and different PTHrP dose(0, 0.01, 0.1, 1 nmol/L) on the proliferation of human osteoblasts were examined using flow cytometry.

RESULTSVarious forces of the mechanical stretching exerted different influences on the intensities of the mRNA' expression. The strain of 12% induced the most remarkable mRNA' expression. The mitogenesis happened in the group with tension force (12%) combined with PTHrP was more active than that in the group with PTHrP or tension' force only. Tension force combined with PTHrP induced significantly more c-fos mRNA than that of tension force only.

CONCLUSIONThe mechanical stretching can inevitably influence the expression of PTHrP mRNA. The most active mitogenesis happened in the group with tension force combined with PTHrP. The effect may be related with the signaling pathways of c-fos.

Cell Line ; Cell Proliferation ; Cells, Cultured ; Humans ; Osteoblasts ; Parathyroid Hormone-Related Protein ; RNA, Messenger